1 00:00:09,800 --> 00:00:14,660 This tiny creature and the silent killer it carries 2 00:00:14,660 --> 00:00:19,460 is the target of one of medical science's greatest quests. 3 00:00:19,460 --> 00:00:23,260 A battle to save millions of lives 4 00:00:23,260 --> 00:00:27,260 and end a scourge that has shaped human history. 5 00:00:27,260 --> 00:00:28,380 Malaria. 6 00:00:29,820 --> 00:00:33,020 - One child dies every single minute from malaria. 7 00:00:33,020 --> 00:00:36,700 - So you might ask yourself, "Why are kids still dying?" 8 00:00:37,860 --> 00:00:42,260 - For almost a century, scientists have had one goal. 9 00:00:42,260 --> 00:00:44,340 - We don't want to use the word the Holy Grail, 10 00:00:44,340 --> 00:00:45,860 but if we got vaccines, 11 00:00:45,860 --> 00:00:48,500 then, of course, that would be transformational. 12 00:00:48,500 --> 00:00:51,060 - The chances of success are really, really small, 13 00:00:51,060 --> 00:00:54,300 but the rewards if you do it are enormous. 14 00:00:54,300 --> 00:00:58,220 - This is the inside story, across four continents, 15 00:00:58,220 --> 00:01:01,060 of a new vaccine against malaria. 16 00:01:01,060 --> 00:01:04,220 - Is Slate 1 up on mine, or is it on yours? - No, but the folder's up... 17 00:01:04,220 --> 00:01:07,380 - It's being made by the same Oxford University team 18 00:01:07,380 --> 00:01:09,980 behind the UK's Covid vaccine. 19 00:01:11,580 --> 00:01:13,380 - We have the head off. 20 00:01:13,380 --> 00:01:16,100 It's those little sacs that have got the parasites in. 21 00:01:16,100 --> 00:01:20,460 - But this time it's an even more complex scientific challenge. 22 00:01:20,460 --> 00:01:23,460 - It didn't work, it didn't work, and it didn't work. 23 00:01:23,460 --> 00:01:26,300 - I remember very openly and straight telling 24 00:01:26,300 --> 00:01:27,980 that this is not going to work. 25 00:01:27,980 --> 00:01:30,980 - And then, after many tweaks and changes... 26 00:01:30,980 --> 00:01:32,660 ..it did. 27 00:01:32,660 --> 00:01:35,340 - Well, to me, it was unthinkable before it happened. 28 00:01:35,340 --> 00:01:38,180 - Another good news story about British vaccines. 29 00:01:38,180 --> 00:01:40,060 It will probably have the biggest impact 30 00:01:40,060 --> 00:01:41,980 on global public health for generations. 31 00:01:41,980 --> 00:01:44,940 It will be up there with clean water. It is that big. 32 00:01:44,940 --> 00:01:46,620 - APPLAUSE 33 00:01:46,620 --> 00:01:48,380 - This could be a game changer. 34 00:01:50,180 --> 00:01:52,620 - You are touching human life. 35 00:01:52,620 --> 00:01:54,540 You are going to save the human life. 36 00:01:54,540 --> 00:01:57,260 It's not one or two. It's millions of lives. 37 00:01:57,260 --> 00:01:59,180 Amazing, isn't it? 38 00:02:17,940 --> 00:02:19,220 - Throughout our history, 39 00:02:19,220 --> 00:02:22,060 the mosquito has been the paramount killer of humanity. 40 00:02:24,260 --> 00:02:27,180 If we look at our Neverland nightmares, we're taught to fear 41 00:02:27,180 --> 00:02:29,540 all these other creatures because they kill so many humans. 42 00:02:29,540 --> 00:02:31,220 That's just simply not true. 43 00:02:31,220 --> 00:02:33,300 For example, wolves and sharks 44 00:02:33,300 --> 00:02:35,900 kill, I think, about ten people per year. 45 00:02:35,900 --> 00:02:38,620 Whereas the mosquito, this tiny little animal 46 00:02:38,620 --> 00:02:40,380 the size and weight of a grape seed, 47 00:02:40,380 --> 00:02:43,980 is responsible for up to a million deaths a year. 48 00:02:46,140 --> 00:02:47,900 But it's not the mosquito itself, 49 00:02:47,900 --> 00:02:50,260 it's the pathogens that hitch a free ride 50 00:02:50,260 --> 00:02:53,820 that cause so much suffering, death and destruction. 51 00:02:53,820 --> 00:02:56,340 Of all the pathogens that mosquitoes carry, 52 00:02:56,340 --> 00:02:59,260 by far the most lethal and the biggest killer of humanity 53 00:02:59,260 --> 00:03:00,740 has been malaria. 54 00:03:07,420 --> 00:03:10,580 - A highly effective vaccine against malaria 55 00:03:10,580 --> 00:03:12,940 would be a historic breakthrough. 56 00:03:12,940 --> 00:03:16,860 And getting there starts with knowing your enemy. 57 00:03:19,060 --> 00:03:22,100 London's Natural History Museum is home 58 00:03:22,100 --> 00:03:25,780 to one of the world's greatest collections of insects. 59 00:03:28,100 --> 00:03:34,260 Senior curator Erica McAlister looks after 150,000 specimens, 60 00:03:34,260 --> 00:03:38,620 representing 2,900 species of mosquito. 61 00:03:41,180 --> 00:03:44,460 - We have maybe 350 drawers of mosquitoes, 62 00:03:44,460 --> 00:03:49,140 but only 20 of those drawers are the species of mosquitoes 63 00:03:49,140 --> 00:03:51,820 that are important for the transmission of malaria. 64 00:03:52,940 --> 00:03:57,220 The difference between the males and the females is very important. 65 00:03:57,220 --> 00:03:58,940 The males are all vegetarian, 66 00:03:58,940 --> 00:04:01,820 but the female has to generate the eggs. 67 00:04:01,820 --> 00:04:05,980 Therefore, she needs a really, really high-protein meal. 68 00:04:05,980 --> 00:04:07,420 The blood. 69 00:04:07,420 --> 00:04:12,180 You've got the proboscis, her fantastically long mouthpart. 70 00:04:12,180 --> 00:04:14,420 It's composed of six stylets. 71 00:04:14,420 --> 00:04:18,580 She uses two of those to kind of, like, penetrate the flesh, 72 00:04:18,580 --> 00:04:21,940 she uses two of them to keep it open, 73 00:04:21,940 --> 00:04:25,620 and then her final two, one is basically a tube 74 00:04:25,620 --> 00:04:27,500 which she will suck up your blood with, 75 00:04:27,500 --> 00:04:30,900 but the other one, through that she releases her saliva 76 00:04:30,900 --> 00:04:33,060 to prevent the blood clotting. 77 00:04:33,060 --> 00:04:36,740 And it is in that process that the malaria parasite 78 00:04:36,740 --> 00:04:39,180 is able to transfer into us. 79 00:04:43,020 --> 00:04:45,220 - NEWSREEL: - Public enemy number one - 80 00:04:45,220 --> 00:04:48,580 Anopheles, the malaria mosquito, 81 00:04:48,580 --> 00:04:52,700 wanted for bringing sickness and misery to untold millions. 82 00:04:54,380 --> 00:04:58,020 - Today, malaria is considered a tropical disease, 83 00:04:58,020 --> 00:05:02,060 but until very recently it affected people worldwide. 84 00:05:04,500 --> 00:05:07,940 And it's played a huge part in our history. 85 00:05:09,380 --> 00:05:12,020 - When we look at European history, for example, 86 00:05:12,020 --> 00:05:15,100 Europeans actually called malaria the Roman fever. 87 00:05:16,540 --> 00:05:20,980 The word malaria - mal aria - actually means bad air in Italian. 88 00:05:20,980 --> 00:05:25,580 So Rome was surrounded by 310 square miles of Pontine Marshes, 89 00:05:25,580 --> 00:05:28,460 which were a hotbed of malarious mosquitoes. 90 00:05:29,460 --> 00:05:34,340 Now, interestingly, they acted as a shield from foreign invasion. 91 00:05:34,340 --> 00:05:36,700 Invaders either couldn't conquer Rome 92 00:05:36,700 --> 00:05:40,020 or had a very brief stay before malaria started to sap the strength 93 00:05:40,020 --> 00:05:42,100 of their troops and they would withdraw. 94 00:05:43,420 --> 00:05:45,340 So it safeguarded and shielded Rome, 95 00:05:45,340 --> 00:05:49,460 allowing for the expansion of Rome, the city, and also the Roman Empire. 96 00:05:50,860 --> 00:05:52,980 - For the next 2,000 years, 97 00:05:52,980 --> 00:05:57,140 malaria-carrying mosquitoes continued to plague most of Europe. 98 00:05:58,860 --> 00:06:01,820 Modern science would not even begin the fightback 99 00:06:01,820 --> 00:06:03,500 until barely a century ago. 100 00:06:05,300 --> 00:06:08,700 - At the dawn of the 20th century, a physician of tropical medicine 101 00:06:08,700 --> 00:06:12,460 remarked that the future of humanity would be decided by one battle - 102 00:06:12,460 --> 00:06:14,460 man versus mosquito. 103 00:06:14,460 --> 00:06:16,780 - All right, men, now we can begin to fight. 104 00:06:16,780 --> 00:06:19,580 - RALLYING BUGLE TUNE 105 00:06:21,740 --> 00:06:26,260 During World War II, military casualties from malaria were so high 106 00:06:26,260 --> 00:06:29,060 that the authorities declared total war, 107 00:06:29,060 --> 00:06:31,860 even recruiting Walt Disney for the fight. 108 00:06:31,860 --> 00:06:33,380 - Attaboy, dopey. 109 00:06:33,380 --> 00:06:35,140 Kill her good and dead. 110 00:06:36,820 --> 00:06:42,220 - The newly invented insecticide DDT destroyed mosquito populations... 111 00:06:43,540 --> 00:06:45,220 ..swamps were drained... 112 00:06:46,620 --> 00:06:49,100 ..protection against bites improved... 113 00:06:50,780 --> 00:06:54,420 ..as did the availability of malaria treatments and tests. 114 00:06:55,860 --> 00:07:00,220 - In the Western world, malaria was made extinct, essentially. 115 00:07:00,220 --> 00:07:02,580 As a result, the malaria burden shifted 116 00:07:02,580 --> 00:07:06,740 to lower socioeconomic countries, specifically in the Global South. 117 00:07:07,900 --> 00:07:11,260 Funding for malaria research was drastically cut, 118 00:07:11,260 --> 00:07:14,980 and malaria was generally all but forgotten in most wealthy nations. 119 00:07:21,340 --> 00:07:25,220 - Nine out of ten people in Tanzania, East Africa, 120 00:07:25,220 --> 00:07:27,500 live in the country's malaria zone. 121 00:07:30,580 --> 00:07:32,580 And it's the youngest children, 122 00:07:32,580 --> 00:07:35,660 naturally much less able to fight off infections, 123 00:07:35,660 --> 00:07:37,100 who are most at risk. 124 00:07:39,820 --> 00:07:43,060 Farhiya Salum is three years old. 125 00:07:43,060 --> 00:07:44,780 She lives in Kiwangwa village 126 00:07:44,780 --> 00:07:49,020 with her mother, Zohara Abasi, a pineapple farmer and small trader, 127 00:07:49,020 --> 00:07:51,420 and her grandmother, Huba Mohamedi. 128 00:09:07,460 --> 00:09:09,940 Across Tanzania and much of Africa, 129 00:09:09,940 --> 00:09:13,620 malaria costs lives and livelihoods, 130 00:09:13,620 --> 00:09:16,260 undermining the potential of an entire continent. 131 00:09:18,420 --> 00:09:22,140 Dr Ally Olotu of the Ifakara Health Institute 132 00:09:22,140 --> 00:09:24,060 serves on the medical front line. 133 00:09:26,380 --> 00:09:29,260 - I got malaria when I was young, 134 00:09:29,260 --> 00:09:32,700 and I also got malaria when I went to the university. 135 00:09:32,700 --> 00:09:35,700 That's when I became aware that this is... 136 00:09:35,700 --> 00:09:37,540 It's an awful disease. 137 00:09:39,740 --> 00:09:43,940 Globally, malaria causes over 200 million cases 138 00:09:43,940 --> 00:09:48,140 and more than 600,000 deaths annually. 139 00:09:48,140 --> 00:09:51,860 About 80% of these deaths are actually young children 140 00:09:51,860 --> 00:09:53,460 below the ages of five. 141 00:10:03,300 --> 00:10:05,340 - Tawakar is three years old, 142 00:10:05,340 --> 00:10:08,060 and was in grave danger of falling into a coma 143 00:10:08,060 --> 00:10:11,300 until he came to the hospital just 24 hours ago. 144 00:10:16,820 --> 00:10:19,580 - Seeing kids who are suffering from malaria, 145 00:10:19,580 --> 00:10:22,340 emotionally it's always difficult. 146 00:10:22,340 --> 00:10:24,020 As a clinician, as a father, 147 00:10:24,020 --> 00:10:28,620 I have to develop interventions to do everything possible 148 00:10:28,620 --> 00:10:30,500 to get rid of malaria. 149 00:10:53,460 --> 00:10:56,900 - While Ally regularly treats children who have been infected... 150 00:10:58,620 --> 00:11:02,380 ..his colleague, mosquito biologist Fredros Okumu, 151 00:11:02,380 --> 00:11:04,500 works on malaria prevention. 152 00:11:07,100 --> 00:11:08,900 - Hey, how are you doing? 153 00:11:08,900 --> 00:11:11,460 How are the mosquitoes today? Have you blood-fed the mosquitoes? 154 00:11:11,460 --> 00:11:12,740 - Yeah. - Uh-huh. 155 00:11:12,740 --> 00:11:16,460 To evaluate specific products for protecting people, 156 00:11:16,460 --> 00:11:18,940 we have to rear the mosquitoes in our labs. 157 00:11:18,940 --> 00:11:20,900 - MOSQUITOES BUZZ 158 00:11:20,900 --> 00:11:23,860 - We have to provide water, sugar and blood. 159 00:11:30,860 --> 00:11:34,260 - Today, it is lab technician Stuart Ngala's turn 160 00:11:34,260 --> 00:11:36,140 to feed the mosquitoes. 161 00:11:42,500 --> 00:11:44,980 MOSQUITOES BUZZ 162 00:11:49,300 --> 00:11:52,340 - The mosquitoes we have in the lab are malaria-free. 163 00:11:52,340 --> 00:11:54,620 It's something that we scientists do. 164 00:11:54,620 --> 00:11:56,340 So, I mean, I do it as well. 165 00:12:01,220 --> 00:12:05,980 - Fredros uses these mosquitoes to test insecticide-treated bed nets. 166 00:12:08,180 --> 00:12:11,540 It's estimated that, over the last 20 years, 167 00:12:11,540 --> 00:12:14,420 tools like these have prevented a staggering 168 00:12:14,420 --> 00:12:18,820 two billion cases of malaria and nearly 12 million deaths. 169 00:12:20,940 --> 00:12:23,020 - Yes, there's been extensive progress. 170 00:12:23,020 --> 00:12:25,660 Is it sufficient progress? 171 00:12:25,660 --> 00:12:29,260 No. Because now we have this challenge since around 2015 172 00:12:29,260 --> 00:12:31,100 where there are many countries in Africa 173 00:12:31,100 --> 00:12:32,980 where malaria cases are going up. 174 00:12:35,180 --> 00:12:37,580 - It's not much killing the mosquito. 175 00:12:37,580 --> 00:12:41,020 - So that particular net didn't kill enough mosquitoes. OK. 176 00:12:42,700 --> 00:12:44,700 The bed nets that we have in the villages 177 00:12:44,700 --> 00:12:47,660 are starting to face a lot of challenges. 178 00:12:47,660 --> 00:12:50,340 Mosquitoes are no longer being killed as effectively 179 00:12:50,340 --> 00:12:52,500 because they have become resistant to the insecticides 180 00:12:52,500 --> 00:12:56,500 that we put on the surface, and so the bed net can lose that quality, 181 00:12:56,500 --> 00:12:57,780 the killing effect. 182 00:13:00,180 --> 00:13:03,420 - You've got mosquitoes that are able to lay hundreds of eggs. 183 00:13:03,420 --> 00:13:06,100 They have some really short generation times. 184 00:13:06,100 --> 00:13:08,580 So some mosquitoes can be, like, two weeks, 185 00:13:08,580 --> 00:13:10,380 and then suddenly you've got a new generation. 186 00:13:10,380 --> 00:13:14,740 So any time they get a new chemical thrown at them, 187 00:13:14,740 --> 00:13:18,060 if it's not done correctly, you can see gene resistance. 188 00:13:18,060 --> 00:13:20,940 And it's like, "Poof!" - game over for that insecticide. 189 00:13:20,940 --> 00:13:22,620 They're so adaptable. 190 00:13:25,900 --> 00:13:28,860 - Despite concerns about increasing resistance, 191 00:13:28,860 --> 00:13:31,060 bed nets treated with insecticide 192 00:13:31,060 --> 00:13:34,420 remain the world's number one weapon against malaria. 193 00:13:36,420 --> 00:13:41,420 But research shows they reduce child deaths by less than 20%. 194 00:13:44,060 --> 00:13:46,340 - We need a transformational tool, 195 00:13:46,340 --> 00:13:48,780 and I do not think there is any medical intervention 196 00:13:48,780 --> 00:13:51,700 that has done better or more than vaccines. 197 00:13:58,100 --> 00:14:02,380 - When it comes to transforming human health and saving lives, 198 00:14:02,380 --> 00:14:06,460 vaccination is up there with clean water and sanitation. 199 00:14:11,780 --> 00:14:16,980 Smallpox, which killed up to 500 million in the 20th century alone, 200 00:14:16,980 --> 00:14:21,460 was eradicated in the 1970s thanks to vaccination. 201 00:14:21,460 --> 00:14:26,180 And there's also been huge success against polio, measles, 202 00:14:26,180 --> 00:14:28,380 and recently Covid-19. 203 00:14:30,620 --> 00:14:34,780 But a highly effective malaria vaccine has never emerged. 204 00:14:36,100 --> 00:14:37,860 That's not for lack of trying. 205 00:14:40,020 --> 00:14:43,820 Ally himself has worked on multiple vaccine candidates. 206 00:14:46,340 --> 00:14:48,660 - So do you know what Daddy's working on? 207 00:14:48,660 --> 00:14:50,540 What am I working on? - Malaria. 208 00:14:50,540 --> 00:14:51,740 - Malaria what? 209 00:14:51,740 --> 00:14:54,300 - Malaria vaccine. - OK. 210 00:14:54,300 --> 00:14:57,020 So that you can...you can protect children, isn't it, 211 00:14:57,020 --> 00:14:58,420 from getting malaria? 212 00:14:58,420 --> 00:15:02,340 - Because children below... under five years who have malaria 213 00:15:02,340 --> 00:15:05,220 are in much bigger danger than others. 214 00:15:05,220 --> 00:15:08,020 - And they die. - Yes, they can die. 215 00:15:08,020 --> 00:15:11,420 But if you go to hospital first, you will survive. 216 00:15:11,420 --> 00:15:15,340 I saw a child three years old who had malaria in the hospital, 217 00:15:15,340 --> 00:15:18,660 but he was treated and he will get better. 218 00:15:18,660 --> 00:15:20,020 But he was very lucky. 219 00:15:22,420 --> 00:15:25,740 As night falls, this is the most vulnerable time. 220 00:15:25,740 --> 00:15:28,460 - MOSQUITO BUZZES - That's when the mosquitoes come in. 221 00:15:31,860 --> 00:15:33,500 When the mosquito bites, 222 00:15:33,500 --> 00:15:36,740 it injects into that child small parasites. 223 00:15:36,740 --> 00:15:38,540 We call them sporozoites. 224 00:15:40,300 --> 00:15:44,180 These spend a very few minutes in the blood, 225 00:15:44,180 --> 00:15:47,700 and then quickly go and start to multiply within the liver. 226 00:15:52,460 --> 00:15:54,420 And these kids could be playing around, 227 00:15:54,420 --> 00:15:55,740 they can be playing football, 228 00:15:55,740 --> 00:15:58,740 they could be singing with their parents. 229 00:15:58,740 --> 00:16:01,420 Nobody can suspect anything. 230 00:16:01,420 --> 00:16:04,420 But from the liver, within a few days, 231 00:16:04,420 --> 00:16:07,700 you could have thousands and thousands of parasites 232 00:16:07,700 --> 00:16:09,460 released into the blood. 233 00:16:10,660 --> 00:16:14,820 They attack our red blood cells, destroying them. 234 00:16:14,820 --> 00:16:18,540 And this is what actually gives rise to malaria symptoms. 235 00:16:21,100 --> 00:16:25,740 That child you saw playing with his friends just a few days ago 236 00:16:25,740 --> 00:16:28,780 can quickly become severely sick. 237 00:16:28,780 --> 00:16:31,860 And if not diagnosed and treated very fast, 238 00:16:31,860 --> 00:16:34,100 that child might lose life. 239 00:16:37,500 --> 00:16:41,020 - It's this process - the way the body is overwhelmed 240 00:16:41,020 --> 00:16:43,460 before it has a chance to fight back - 241 00:16:43,460 --> 00:16:46,700 that makes malaria so dangerous, 242 00:16:46,700 --> 00:16:50,020 and the development of a vaccine so challenging. 243 00:16:51,020 --> 00:16:53,780 - We have developed vaccines for other diseases, of course, 244 00:16:53,780 --> 00:16:56,460 but most of these are viruses and bacteria, 245 00:16:56,460 --> 00:17:00,700 which are much simpler pathogens compared to malaria. 246 00:17:00,700 --> 00:17:03,500 It's a very complex parasite. 247 00:17:03,500 --> 00:17:08,220 So I was really excited to be part of the consortium of scientists 248 00:17:08,220 --> 00:17:10,660 put together by the University of Oxford 249 00:17:10,660 --> 00:17:12,580 to work on a new malaria vaccine. 250 00:17:16,460 --> 00:17:20,380 - The University of Oxford is home to one of the world's largest 251 00:17:20,380 --> 00:17:23,140 academic vaccine development programmes. 252 00:17:24,900 --> 00:17:28,700 In 2020, the university's Jenner Institute 253 00:17:28,700 --> 00:17:33,100 created the Oxford AstraZeneca Covid-19 vaccine. 254 00:17:33,100 --> 00:17:38,860 And, since then, 3 billion doses have reached 170 countries. 255 00:17:42,580 --> 00:17:44,380 Adrian Hill and his colleagues 256 00:17:44,380 --> 00:17:47,620 have found malaria much more difficult. 257 00:17:47,620 --> 00:17:49,620 - We've known for over 100 years 258 00:17:49,620 --> 00:17:52,260 that it would be fantastic to have a malaria vaccine. 259 00:17:52,260 --> 00:17:55,420 People have been trying for about 120 years, 260 00:17:55,420 --> 00:17:57,500 ever since the parasite was discovered. 261 00:18:00,100 --> 00:18:03,620 I did a count about six months ago of how many vaccines had been made 262 00:18:03,620 --> 00:18:07,100 and gone into clinical trials for malaria, how many different ones, 263 00:18:07,100 --> 00:18:09,900 and that number was 142. 264 00:18:09,900 --> 00:18:11,500 I'm not sure there's another disease 265 00:18:11,500 --> 00:18:14,580 where there have been that many vaccines that didn't work. 266 00:18:21,780 --> 00:18:25,300 - Katie Ewer is the lead immunologist on the Oxford team. 267 00:18:27,620 --> 00:18:31,380 - I think malaria is more personal for me because it's children. 268 00:18:31,380 --> 00:18:33,500 I think you'd have to be a very hard-hearted person 269 00:18:33,500 --> 00:18:37,580 not to be moved by a death toll of 400,000 kids a year dying in Africa, 270 00:18:37,580 --> 00:18:39,620 under the age of five, from malaria. 271 00:18:41,580 --> 00:18:43,980 It's a huge motivator to work on something 272 00:18:43,980 --> 00:18:47,860 where the chances of success are really, really small. 273 00:18:47,860 --> 00:18:50,820 But the rewards, if you do it, are enormous. 274 00:18:55,460 --> 00:18:59,660 - For the last 13 years, the Oxford team has been working on a vaccine 275 00:18:59,660 --> 00:19:01,780 called R21. 276 00:19:03,700 --> 00:19:07,540 Its goal is to fire up the body's immune defences, 277 00:19:07,540 --> 00:19:12,180 to be ready to attack the parasite at its most vulnerable moment - 278 00:19:12,180 --> 00:19:14,700 just after it enters our blood. 279 00:19:16,180 --> 00:19:19,820 - When an infected female mosquito takes a bite 280 00:19:19,820 --> 00:19:22,900 and injects sporozoites - malaria parasites - 281 00:19:22,900 --> 00:19:25,660 there's about a half-hour to two-hour window 282 00:19:25,660 --> 00:19:28,260 before the parasites invade the cells in your body 283 00:19:28,260 --> 00:19:29,660 and set up infection there. 284 00:19:29,660 --> 00:19:32,820 And that's the window that we're trying to target with our vaccine. 285 00:19:33,860 --> 00:19:35,660 - What all vaccines must do 286 00:19:35,660 --> 00:19:39,620 is mobilise the immune system's front line defence against invaders. 287 00:19:40,860 --> 00:19:42,780 An army of antibodies. 288 00:19:45,380 --> 00:19:49,300 Their goal is to quickly neutralise any invading pathogens... 289 00:19:50,420 --> 00:19:53,500 ..by tightly binding to their surface, 290 00:19:53,500 --> 00:19:56,140 stopping them in their tracks, 291 00:19:56,140 --> 00:19:58,500 and marking them for destruction. 292 00:20:01,100 --> 00:20:03,540 - The problem has been to produce enough antibodies 293 00:20:03,540 --> 00:20:06,940 to clear all of those parasites very quickly. 294 00:20:06,940 --> 00:20:09,900 - Threatened by just a few invading parasites, 295 00:20:09,900 --> 00:20:13,580 our antibody response is usually too little, too late. 296 00:20:14,780 --> 00:20:19,100 But luckily, the malaria sporozoite has an Achilles' heel. 297 00:20:20,660 --> 00:20:25,380 To invade the liver, it relies on a coating called CSP - 298 00:20:25,380 --> 00:20:27,740 the circumsporozoite protein. 299 00:20:29,300 --> 00:20:32,900 - What we need are large amounts of very specific antibodies 300 00:20:32,900 --> 00:20:37,740 that bind as tightly as possible to the circumsporozoite protein. 301 00:20:37,740 --> 00:20:40,020 Then we should be able to stop the parasites 302 00:20:40,020 --> 00:20:41,780 before they can reach the liver. 303 00:20:44,100 --> 00:20:47,380 - This is where the R21 vaccine comes in. 304 00:20:48,380 --> 00:20:51,500 It is built from the CSP protein, 305 00:20:51,500 --> 00:20:56,180 and so induces the body to produce antibodies tailor-made and ready 306 00:20:56,180 --> 00:20:58,180 to neutralise the parasite. 307 00:21:00,580 --> 00:21:02,740 But this is not a new idea. 308 00:21:04,340 --> 00:21:09,900 First designed in 1987, a vaccine called RTS,S already does this. 309 00:21:12,260 --> 00:21:15,900 - I've had privilege to work on RTS,S malaria vaccine, 310 00:21:15,900 --> 00:21:20,740 and the overall efficacy of RTS,S is about 40% 311 00:21:20,740 --> 00:21:23,020 against clinical disease. 312 00:21:23,020 --> 00:21:26,620 40% may sound as not very good efficacy, 313 00:21:26,620 --> 00:21:29,860 but you have to think about the burden of malaria. 314 00:21:29,860 --> 00:21:33,380 We have well over 600,000 deaths annually, 315 00:21:33,380 --> 00:21:38,100 so saving or reducing the burden by 40% is better than nothing. 316 00:21:41,580 --> 00:21:43,620 - After lengthy deliberations, 317 00:21:43,620 --> 00:21:48,540 in 2022, RTS,S became the first malaria vaccine 318 00:21:48,540 --> 00:21:52,780 approved by the WHO - the World Health Organization - 319 00:21:52,780 --> 00:21:56,180 35 years after it was initially developed. 320 00:21:57,620 --> 00:22:02,780 But RTS,S is expensive to produce, supply is currently limited, 321 00:22:02,780 --> 00:22:05,860 and it falls short of the WHO's own target 322 00:22:05,860 --> 00:22:09,940 of having a 75% effective vaccine by 2030. 323 00:22:12,340 --> 00:22:16,740 And so the Oxford team had long set their sights on an upgrade. 324 00:22:17,780 --> 00:22:19,740 - R21 was born out of the idea 325 00:22:19,740 --> 00:22:23,020 that perhaps we could make a slightly better version of RTS,S. 326 00:22:23,020 --> 00:22:26,100 So it started with a PhD student called Kat Collins 327 00:22:26,100 --> 00:22:28,100 taking this on as her project. 328 00:22:29,660 --> 00:22:34,180 - The RTS,S vaccine is made of billions of tiny particles. 329 00:22:35,580 --> 00:22:41,060 They're built from a virus protein that forms a harmless, empty shell, 330 00:22:41,060 --> 00:22:46,700 and part of the same CSP protein that coats the malaria parasite. 331 00:22:46,700 --> 00:22:50,860 Together, they trigger the body's immune response. 332 00:22:50,860 --> 00:22:53,420 But unlike the malaria parasite, 333 00:22:53,420 --> 00:22:57,180 less than a quarter of each particle's surface is CSP. 334 00:22:58,420 --> 00:23:01,860 Kat Collins and her Oxford colleagues wondered, 335 00:23:01,860 --> 00:23:06,860 could increasing the amount of CSP to better mimic the malaria parasite 336 00:23:06,860 --> 00:23:08,460 make a better vaccine? 337 00:23:10,220 --> 00:23:14,580 - We kept on trying different ways to get that to form into a particle, 338 00:23:14,580 --> 00:23:18,020 and it didn't work, it didn't work, and it didn't work. 339 00:23:18,020 --> 00:23:21,980 And eventually, after many tweaks and changes... 340 00:23:21,980 --> 00:23:23,020 ..it did. 341 00:23:24,060 --> 00:23:25,300 That was a big day. 342 00:23:27,180 --> 00:23:29,060 You can literally see these particles 343 00:23:29,060 --> 00:23:30,740 with an electron microscope. 344 00:23:30,740 --> 00:23:33,660 And, boy, those images are memorable. 345 00:23:33,660 --> 00:23:35,780 We managed to cover all of the surface 346 00:23:35,780 --> 00:23:40,100 of every R21 particle in CSP. 347 00:23:40,100 --> 00:23:43,100 We thought, "Fantastic!" We immunised mice, and guess what? 348 00:23:43,100 --> 00:23:45,660 They were nearly all protected very well. 349 00:23:45,660 --> 00:23:47,380 This was 2012. 350 00:23:47,380 --> 00:23:48,900 We were finally getting there. 351 00:23:48,900 --> 00:23:53,140 And, of course, getting there means you're ready to try and manufacture 352 00:23:53,140 --> 00:23:54,940 and go into the clinic. 353 00:24:00,620 --> 00:24:05,340 - Oxford University's R21 was doing exactly as they'd hoped, 354 00:24:05,340 --> 00:24:08,860 creating a strong protective immune response. 355 00:24:08,860 --> 00:24:11,460 But that was just in mice. 356 00:24:11,460 --> 00:24:15,020 The big challenge now would be testing it in humans. 357 00:24:17,180 --> 00:24:20,100 For this, they called on Eleanor Berrie, 358 00:24:20,100 --> 00:24:23,660 a specialist in vaccine manufacture for human trials. 359 00:24:24,980 --> 00:24:29,300 - Vaccines are actually one of the most complicated things 360 00:24:29,300 --> 00:24:30,820 you can manufacture. 361 00:24:30,820 --> 00:24:37,140 But Adrian and Kat were so enthusiastic about R21, 362 00:24:37,140 --> 00:24:41,220 they had generated some excellent preclinical data, 363 00:24:41,220 --> 00:24:44,060 and that enthusiasm rubs off on you. 364 00:24:44,060 --> 00:24:48,340 So, you know, you begin to feel, "Yeah, we could do this." 365 00:24:48,340 --> 00:24:49,460 Yeah. 366 00:24:50,580 --> 00:24:54,500 - Eleanor and her team only needed to make enough R21 367 00:24:54,500 --> 00:24:57,540 to inject a small number of healthy people, 368 00:24:57,540 --> 00:25:00,140 less than half a cup's worth, 369 00:25:00,140 --> 00:25:03,740 but thousands of times more than Adrian's team had created 370 00:25:03,740 --> 00:25:05,940 in the lab for their mouse tests. 371 00:25:06,940 --> 00:25:09,900 And this time with human safety on the line. 372 00:25:12,420 --> 00:25:17,820 - I've always had the ethos, the feeling that... 373 00:25:19,220 --> 00:25:23,020 .."Am I happy for this product to go into somebody?" 374 00:25:23,020 --> 00:25:25,220 And the best analogy I can use is, 375 00:25:25,220 --> 00:25:27,540 "Would I inject it into one of my two children?" 376 00:25:27,540 --> 00:25:31,980 And if I can categorically say yes, then I feel reassured 377 00:25:31,980 --> 00:25:35,420 in the knowledge that we've done everything we possibly can 378 00:25:35,420 --> 00:25:38,740 to produce a safe product. 379 00:25:41,660 --> 00:25:47,540 We started the project in 2012, and took us three and a half years. 380 00:25:48,540 --> 00:25:51,220 If we had been in a commercial situation, 381 00:25:51,220 --> 00:25:53,740 I would think that they would have just... 382 00:25:54,860 --> 00:25:57,500 ..stopped the project on many occasions. 383 00:25:57,500 --> 00:26:01,940 - We kept going and kept spending and finding and spending more money 384 00:26:01,940 --> 00:26:03,980 to get it manufactured. 385 00:26:03,980 --> 00:26:08,820 - The major feeling was just a sense of relief that we had got there. 386 00:26:10,620 --> 00:26:15,940 - The 10th of November 2015, 85 vials certified. 387 00:26:16,980 --> 00:26:18,700 Three doses per person. 388 00:26:18,700 --> 00:26:21,020 20 to 30 people, that would cover. 389 00:26:21,020 --> 00:26:23,500 Not exactly vaccinating the world, is it? 390 00:26:23,500 --> 00:26:25,020 But it's where we started. 391 00:26:26,740 --> 00:26:30,140 - With these precious few doses of R21, 392 00:26:30,140 --> 00:26:33,860 the Oxford team began small-scale human trials. 393 00:26:33,860 --> 00:26:38,780 First, they mixed the vaccine with a substance called Matrix-M, 394 00:26:38,780 --> 00:26:41,860 which helps strengthen the immune response. 395 00:26:41,860 --> 00:26:44,260 They injected 28 healthy adults 396 00:26:44,260 --> 00:26:48,980 and reported it induced an antibody response comparable to RTS,S 397 00:26:48,980 --> 00:26:51,220 at a much lower vaccine dose. 398 00:26:52,220 --> 00:26:55,460 Next, they purposely exposed a few vaccinated people 399 00:26:55,460 --> 00:27:00,420 to infectious mosquitos in what's known as a malaria challenge trial 400 00:27:00,420 --> 00:27:03,380 and found that they were protected from malaria. 401 00:27:04,820 --> 00:27:09,860 Such exciting early results drew attention beyond Oxford. 402 00:27:09,860 --> 00:27:12,820 - Word had got around. We academics talk at meetings, 403 00:27:12,820 --> 00:27:14,620 and you never know who's in the room, 404 00:27:14,620 --> 00:27:17,580 but my guess is there was somebody from the Serum Institute of India, 405 00:27:17,580 --> 00:27:20,980 and the next month, Umesh Shaligram turned up here 406 00:27:20,980 --> 00:27:22,700 wanting to talk about malaria. 407 00:27:24,100 --> 00:27:27,620 - Certainly, Oxford data was very convincing, early data, 408 00:27:27,620 --> 00:27:31,620 so that certainly made a big difference in our conviction. 409 00:27:31,620 --> 00:27:34,620 - They'd heard about the initial challenge results. 410 00:27:34,620 --> 00:27:36,500 They came to us. 411 00:27:36,500 --> 00:27:38,580 Normally, we go begging to companies, 412 00:27:38,580 --> 00:27:40,060 asking them to work with us. 413 00:27:40,060 --> 00:27:43,020 - We made a kind of a handshake deal 414 00:27:43,020 --> 00:27:46,180 that we could manufacture the product. 415 00:27:46,180 --> 00:27:48,020 That's how the whole thing started. 416 00:27:54,620 --> 00:27:58,940 - The Serum Institute of India is the largest vaccine manufacturer 417 00:27:58,940 --> 00:28:00,260 in the world. 418 00:28:02,100 --> 00:28:05,180 Two thirds of all babies born globally 419 00:28:05,180 --> 00:28:08,260 get at least one of Serum's childhood vaccines, 420 00:28:08,260 --> 00:28:09,740 made here in Pune. 421 00:28:11,460 --> 00:28:15,700 It's made this family-run company a global life-saver 422 00:28:15,700 --> 00:28:19,780 and CEO Adar Poonawalla a multi-billionaire. 423 00:28:22,500 --> 00:28:24,540 - Every time we look at a vaccine, 424 00:28:24,540 --> 00:28:26,820 the way we look at it is that, unless we can make 425 00:28:26,820 --> 00:28:29,300 hundreds of millions of doses for the whole world, 426 00:28:29,300 --> 00:28:33,420 and unless it has that need and demand, we don't get into it. 427 00:28:33,420 --> 00:28:35,940 Ah, Beto, what's happening? 428 00:28:35,940 --> 00:28:39,780 These are very large populations, so they need a lot of vaccines. 429 00:28:39,780 --> 00:28:43,780 It would be unimaginable if they had to pay $10, $20 for a vaccine. 430 00:28:43,780 --> 00:28:45,940 They wouldn't be able to afford it. 431 00:28:45,940 --> 00:28:48,700 We charge pennies on the dollar for the vaccine, 432 00:28:48,700 --> 00:28:51,660 but the economies of scale that we operate at 433 00:28:51,660 --> 00:28:54,780 enable us to do that and still make a modest profit. 434 00:28:54,780 --> 00:28:56,500 You can go ahead with that. 435 00:28:59,500 --> 00:29:04,100 - In 2017, Serum took over manufacturing R21 436 00:29:04,100 --> 00:29:08,140 and spent two years developing a new, reliable method 437 00:29:08,140 --> 00:29:09,860 to produce it at scale. 438 00:29:12,580 --> 00:29:16,260 The team chose the West African country Burkina Faso, 439 00:29:16,260 --> 00:29:19,660 where around half the population gets malaria each year, 440 00:29:19,660 --> 00:29:22,420 for the vaccine's first real-world test. 441 00:29:25,100 --> 00:29:29,300 In 2019, 450 very young children, 442 00:29:29,300 --> 00:29:31,620 the group most in need of protection, 443 00:29:31,620 --> 00:29:34,220 were vaccinated in a phase 2 trial. 444 00:29:35,260 --> 00:29:38,500 For success, these babies would have to experience 445 00:29:38,500 --> 00:29:40,900 no unexpected side effects, 446 00:29:40,900 --> 00:29:44,100 and they would need to be a significant reduction 447 00:29:44,100 --> 00:29:47,580 in malaria cases in those who received R21. 448 00:29:51,460 --> 00:29:54,060 The UK team waited for news. 449 00:29:55,380 --> 00:29:58,060 - It was actually my colleague, Mehreen, who said, 450 00:29:58,060 --> 00:30:00,460 "Look at your email, we've got the results." 451 00:30:00,460 --> 00:30:04,660 77% efficacy, as good as we could possibly have hoped. 452 00:30:04,660 --> 00:30:07,540 - I wasn't even sure that I could quite believe what I was reading. 453 00:30:07,540 --> 00:30:09,820 You know, we showed that the vaccine, 454 00:30:09,820 --> 00:30:15,500 albeit just over six months, had worked in the target population 455 00:30:15,500 --> 00:30:17,460 in the target age group. 456 00:30:17,460 --> 00:30:21,420 But if you've seen really good results, you know what's coming. 457 00:30:21,420 --> 00:30:24,100 Large-scale phase 3 trials. 458 00:30:24,100 --> 00:30:26,580 Definitely a very daunting prospect. 459 00:30:29,700 --> 00:30:33,420 - Phase 3 is the largest clinical trial. 460 00:30:33,420 --> 00:30:35,780 It'll need to be big enough to determine 461 00:30:35,780 --> 00:30:41,660 if R21 can safely prevent malaria in thousands of children. 462 00:30:41,660 --> 00:30:45,340 And this will cost around $20 million. 463 00:30:46,540 --> 00:30:50,700 - Me and Adrian went almost every door-to-door 464 00:30:50,700 --> 00:30:53,100 and tried to search for the funding. 465 00:30:53,100 --> 00:30:57,660 Somebody should support us, and we had a really tough time. 466 00:30:57,660 --> 00:30:59,180 - We were fighting for funding 467 00:30:59,180 --> 00:31:03,100 against people dealing with other very important medical diseases. 468 00:31:03,100 --> 00:31:07,660 People are more likely to try and invest in something that sounds new 469 00:31:07,660 --> 00:31:10,540 than the old idea of making a vaccine against malaria, 470 00:31:10,540 --> 00:31:13,180 which has failed and failed and failed over decades. 471 00:31:14,420 --> 00:31:19,340 - After a year's try, I remember I said, "Mr Poonawalla, sir, 472 00:31:19,340 --> 00:31:20,940 "I'm having a big challenge 473 00:31:20,940 --> 00:31:23,900 "of getting the funding for the phase 3." 474 00:31:23,900 --> 00:31:27,580 And he said, "No, no, don't worry. Malaria is very close to my heart, 475 00:31:27,580 --> 00:31:30,900 "and I want to support the phase 3." 476 00:31:30,900 --> 00:31:35,620 - The Serum Institute's CEO agrees to fund the trial. 477 00:31:35,620 --> 00:31:37,940 - The results have demonstrated that the vaccine 478 00:31:37,940 --> 00:31:40,020 is giving you protection. 479 00:31:40,020 --> 00:31:41,860 So, instead of wasting time, 480 00:31:41,860 --> 00:31:44,260 we just wanted to get on with the work. 481 00:31:47,900 --> 00:31:52,060 - In April 2021, phase 3 trial preparations begin 482 00:31:52,060 --> 00:31:57,060 in Burkina Faso, Mali, Kenya, and here in Tanzania. 483 00:32:00,500 --> 00:32:04,260 Mehreen Datoo is a British infectious diseases doctor... 484 00:32:05,540 --> 00:32:11,020 ..but her key role on the R21 team is to oversee its ultimate test. 485 00:32:12,380 --> 00:32:14,740 - What we wanted to propose today to do 486 00:32:14,740 --> 00:32:17,980 is a mock-up vaccine preparation for us, 487 00:32:17,980 --> 00:32:20,580 just to check it's all running smoothly. 488 00:32:20,580 --> 00:32:24,820 - Nearly 5,000 very young children are set to receive shots 489 00:32:24,820 --> 00:32:28,700 in the phase 3 trial - hundreds of them in Tanzania. 490 00:32:31,740 --> 00:32:35,100 For every two children that receive R21, 491 00:32:35,100 --> 00:32:37,980 one child will receive a control vaccine. 492 00:32:38,980 --> 00:32:41,780 In this case, a vaccine against rabies. 493 00:32:43,060 --> 00:32:45,420 This should look just like R21 494 00:32:45,420 --> 00:32:48,300 but offer no protection at all from malaria. 495 00:32:49,620 --> 00:32:52,860 - The rabies vaccine is a good option because it's not a vaccine 496 00:32:52,860 --> 00:32:56,260 that children would normally receive in that part of the world, 497 00:32:56,260 --> 00:32:58,700 so it does provide some benefit. 498 00:33:00,220 --> 00:33:03,900 - Crucially, Mehreen and almost everyone involved 499 00:33:03,900 --> 00:33:07,140 is blind to which vaccine each child receives... 500 00:33:08,220 --> 00:33:11,940 ..so they must monitor cases of malaria across the whole trial 501 00:33:11,940 --> 00:33:17,180 and only learn much later if those cases were in the R21 vaccine group 502 00:33:17,180 --> 00:33:19,660 or the control group. 503 00:33:19,660 --> 00:33:22,740 - The only people that are unblinded are the pharmacy team, 504 00:33:22,740 --> 00:33:25,060 who prepare the vaccine. 505 00:33:25,060 --> 00:33:27,500 You want to make sure the whole volume is covered. 506 00:33:27,500 --> 00:33:29,900 The whole idea of this is to not know which vaccine 507 00:33:29,900 --> 00:33:32,180 the child has received, to ensure there's no bias. 508 00:33:32,180 --> 00:33:34,900 It means that, you know, we will get the most accurate data. 509 00:33:34,900 --> 00:33:37,020 That's why there's two of you to do it. 510 00:33:37,020 --> 00:33:40,540 There's always a spare pair of hands. 511 00:33:40,540 --> 00:33:43,140 - CHATTER 512 00:33:47,180 --> 00:33:49,980 - My family are actually from East Africa. 513 00:33:49,980 --> 00:33:52,540 Unfortunately, when I was doing some research there previously, 514 00:33:52,540 --> 00:33:55,620 I got malaria, and I was very, very sick. 515 00:33:56,620 --> 00:33:58,540 I basically fainted and collapsed 516 00:33:58,540 --> 00:34:01,020 and then was diagnosed with severe malaria. 517 00:34:01,020 --> 00:34:04,300 I don't remember a lot of it because I was just very, very unwell. 518 00:34:05,660 --> 00:34:07,900 I was in my early 20s, 519 00:34:07,900 --> 00:34:11,700 so I can't even imagine how it affects very young children. 520 00:34:17,940 --> 00:34:19,580 - Here in Tanzania, 521 00:34:19,580 --> 00:34:22,420 Dr Ally Olotu is managing the vaccination 522 00:34:22,420 --> 00:34:25,380 and monitoring of 600 children. 523 00:34:37,980 --> 00:34:39,140 - OK. 524 00:34:52,460 --> 00:34:55,620 - In late 2022, a precious cargo arrives 525 00:34:55,620 --> 00:34:58,820 at the Kiwangwa Clinic from India. 526 00:35:01,380 --> 00:35:05,100 After an initial three doses of either R21 527 00:35:05,100 --> 00:35:07,300 or the rabies control vaccine, 528 00:35:07,300 --> 00:35:10,500 a one-year booster shot is now being prepared 529 00:35:10,500 --> 00:35:13,460 for Farhiya and the other trial participants. 530 00:35:40,420 --> 00:35:43,580 For Zuhura Abbasi, vaccination is about much more 531 00:35:43,580 --> 00:35:47,380 than simply preventing her daughter from falling ill. 532 00:36:03,620 --> 00:36:05,020 SIZZLING 533 00:36:40,060 --> 00:36:41,900 CHATTER 534 00:36:43,660 --> 00:36:46,220 For families and scientists alike, 535 00:36:46,220 --> 00:36:49,020 Vaccination Day is special. 536 00:36:49,020 --> 00:36:51,980 - They all look relatively happy. No-one's crying. 537 00:36:51,980 --> 00:36:53,700 - Yeah, yeah, absolutely. 538 00:36:55,100 --> 00:36:57,380 - Really nice to see the relationships the trial team 539 00:36:57,380 --> 00:36:59,740 have with the participants and the caregivers, 540 00:36:59,740 --> 00:37:02,980 because I think that makes it, you know, almost a bit more like family. 541 00:37:22,220 --> 00:37:24,860 - TEAM EXCLAIMS AND APPLAUDS 542 00:37:24,860 --> 00:37:28,820 After vaccination, Farhiya and the other children in the trial 543 00:37:28,820 --> 00:37:32,140 are closely monitored for signs of malaria. 544 00:37:32,140 --> 00:37:34,860 The vaccine's success or failure 545 00:37:34,860 --> 00:37:38,540 will depend on how many malaria cases occur in children 546 00:37:38,540 --> 00:37:42,300 who received R21 versus the control vaccine. 547 00:37:44,740 --> 00:37:48,300 While they wait for this result, the team is also investigating 548 00:37:48,300 --> 00:37:51,140 what the vaccine is doing inside the body. 549 00:37:54,340 --> 00:37:57,740 For that, they have to study the children's blood. 550 00:38:00,540 --> 00:38:05,140 - We can now measure the amount of antibodies that are in the blood. 551 00:38:06,980 --> 00:38:10,740 Some of this will be shipped into a reference lab in Oxford, 552 00:38:10,740 --> 00:38:13,100 where samples from other sites 553 00:38:13,100 --> 00:38:16,420 which are participating will be analysed. 554 00:38:23,220 --> 00:38:26,820 - As phase 3 booster vaccinations proceed, 555 00:38:26,820 --> 00:38:29,380 immunologist Katie Ewer and her team 556 00:38:29,380 --> 00:38:32,780 are deluged with these blood samples. 557 00:38:32,780 --> 00:38:34,700 - There's absolutely loads still to do. 558 00:38:34,700 --> 00:38:37,740 I have a freezer full of thousands of samples from the phase 3 559 00:38:37,740 --> 00:38:40,340 that we haven't had a chance to start looking at yet. 560 00:38:44,060 --> 00:38:46,500 Having had, very recently, the experience 561 00:38:46,500 --> 00:38:48,900 of taking a vaccine through to phase 3 for Covid, 562 00:38:48,900 --> 00:38:50,780 where we had an enormous team of people 563 00:38:50,780 --> 00:38:52,380 and AstraZeneca working on it, 564 00:38:52,380 --> 00:38:54,740 the contrast to the team working on malaria, 565 00:38:54,740 --> 00:38:58,340 where there are seven of us, it's a very different experience. 566 00:38:59,540 --> 00:39:02,060 - You've got the timer? Great. - BEEPING 567 00:39:03,060 --> 00:39:06,660 We're under pressure to start churning out some data, 568 00:39:06,660 --> 00:39:08,420 so it's full speed ahead. 569 00:39:08,420 --> 00:39:10,820 Is plate one up on mine or is it on yours? 570 00:39:10,820 --> 00:39:12,300 - No, but the folder's up... - OK. 571 00:39:12,300 --> 00:39:15,500 - The team needs to analyse the children's antibody responses 572 00:39:15,500 --> 00:39:19,260 to R21 and the control vaccine. 573 00:39:19,260 --> 00:39:23,820 Immunologist Lisa Stockdale is running a test called an ELISA. 574 00:39:23,820 --> 00:39:25,620 - We've got quite a big variation. 575 00:39:25,620 --> 00:39:28,260 Some of the samples have quite a lot of antibody, 576 00:39:28,260 --> 00:39:30,140 whereas some of them don't. 577 00:39:30,140 --> 00:39:32,340 We're blinded to which group people are in, 578 00:39:32,340 --> 00:39:35,980 but in general, it looks like the plate's developing well. 579 00:39:35,980 --> 00:39:38,420 I've been doing hundreds of these ELISA plates. 580 00:39:38,420 --> 00:39:40,820 - SHE CHUCKLES Hundreds and hundreds. 581 00:39:42,260 --> 00:39:45,580 To be effective, R21 must prime the blood 582 00:39:45,580 --> 00:39:49,900 with antibodies that target the malaria CSP protein. 583 00:39:49,900 --> 00:39:52,060 But the team also needs to know 584 00:39:52,060 --> 00:39:57,180 if those antibodies can actually neutralise REAL malaria parasites. 585 00:39:57,180 --> 00:40:00,820 - We take the parasites out by dissecting a mosquito. 586 00:40:00,820 --> 00:40:03,340 And so, I'm just going to hold it with one hand. 587 00:40:04,620 --> 00:40:07,260 Pull the head away...gently. 588 00:40:08,860 --> 00:40:12,060 OK, so we have the head off. 589 00:40:13,180 --> 00:40:16,180 You end up with two pairs of salivary glands. 590 00:40:16,180 --> 00:40:18,740 They look like little, fat sausages. 591 00:40:18,740 --> 00:40:21,660 It's those little sacs that have got the parasites in. 592 00:40:25,820 --> 00:40:27,460 Aha! Got them. 593 00:40:28,660 --> 00:40:31,820 - The parasites are added to lab-grown liver cells, 594 00:40:31,820 --> 00:40:34,220 along with blood from vaccinated children. 595 00:40:36,100 --> 00:40:39,220 If the liver cells do not become infected, 596 00:40:39,220 --> 00:40:42,940 it suggests the antibodies should protect the children, too. 597 00:40:45,700 --> 00:40:47,940 - There's just a lot of pressure to get through all these samples 598 00:40:47,940 --> 00:40:49,900 to get the antibody data together. 599 00:40:49,900 --> 00:40:52,740 Should we do both of them together now? 600 00:40:52,740 --> 00:40:54,260 - Could do. 601 00:40:54,260 --> 00:40:57,060 - I am getting emails at two or three in the morning. 602 00:40:57,060 --> 00:41:00,220 So a lot of people are working super hard. 603 00:41:00,220 --> 00:41:04,260 I'm a little bit anxious that maybe we've had to push them too hard 604 00:41:04,260 --> 00:41:06,780 or were too ambitious in our timeline. 605 00:41:09,740 --> 00:41:10,860 - I'm exhausted. 606 00:41:12,060 --> 00:41:15,420 I'm tired. I'm stressed. I'm not sleeping. 607 00:41:15,420 --> 00:41:18,860 Er, yeah, I'm probably not a great person to be around at the moment, 608 00:41:18,860 --> 00:41:20,300 if I'm honest. 609 00:41:21,580 --> 00:41:26,660 - All this lab effort is crucial to understanding how R21 works. 610 00:41:28,300 --> 00:41:30,620 But, above all, they need to know 611 00:41:30,620 --> 00:41:34,300 if the vaccine protects enough children in the real world. 612 00:41:37,100 --> 00:41:40,260 After around a year of closely monitoring the health 613 00:41:40,260 --> 00:41:44,180 of all 4,800 phase 3 children, 614 00:41:44,180 --> 00:41:46,260 the wait is nearly over. 615 00:41:54,260 --> 00:41:59,340 - The key phase 3 trial is coming to the end point. 616 00:41:59,340 --> 00:42:01,380 The statisticians have the data 617 00:42:01,380 --> 00:42:05,140 and they are analysing it as we speak. 618 00:42:07,220 --> 00:42:09,620 - You know, this is something that we've all worked on for years. 619 00:42:09,620 --> 00:42:11,420 So to be this close, 620 00:42:11,420 --> 00:42:14,980 it's kind of nauseatingly, sickeningly 621 00:42:14,980 --> 00:42:16,780 anxiety-inducing, really. 622 00:42:18,300 --> 00:42:20,220 You know, we just don't know what we're going to see. 623 00:42:20,220 --> 00:42:24,460 Um, and I think we'll be all really relieved to get that result. 624 00:42:24,460 --> 00:42:29,220 - 11 years after R21 was first made here in the lab, 625 00:42:29,220 --> 00:42:34,060 after seven years of trials, over 20,000 vaccinations, 626 00:42:34,060 --> 00:42:37,060 and hundreds of thousands of samples analysed... 627 00:42:38,300 --> 00:42:39,540 ..an answer. 628 00:42:41,620 --> 00:42:43,860 - Even got significance on severe malaria. 629 00:42:43,860 --> 00:42:45,140 - 73%... Bloody hell! 630 00:42:45,140 --> 00:42:47,460 - With wide confidence intervals, but bloody hell, that's... 631 00:42:47,460 --> 00:42:49,460 - I mean, that... Yeah, absolutely. 632 00:42:50,780 --> 00:42:51,820 Great. 633 00:42:52,900 --> 00:42:55,260 Oh, God, get me a drink! 634 00:42:55,260 --> 00:42:56,660 Oh! 635 00:42:57,740 --> 00:42:59,980 - Yeah. - SHE SIGHS 636 00:42:59,980 --> 00:43:02,380 So we have the result of the phase 3. 637 00:43:02,380 --> 00:43:04,660 Um, so a big moment. Um... 638 00:43:06,580 --> 00:43:08,980 As expected from the phase 2, 639 00:43:08,980 --> 00:43:11,140 so really interesting results in there, 640 00:43:11,140 --> 00:43:14,420 but, yeah, really good and really reassuring, and... 641 00:43:14,420 --> 00:43:16,340 Yeah, just very happy. 642 00:43:16,340 --> 00:43:18,340 - SHE LAUGHS TEARFULLY 643 00:43:21,940 --> 00:43:24,700 SHE SOBS 644 00:43:36,220 --> 00:43:37,860 - Yeah, we're very happy. 645 00:43:37,860 --> 00:43:39,700 Although it probably doesn't look like it! 646 00:43:39,700 --> 00:43:43,540 But, yeah, it's just a moment I've been waiting for for so long. 647 00:43:45,300 --> 00:43:49,140 But, yeah, what we wanted and what we hoped for, so really good. 648 00:43:50,340 --> 00:43:51,500 Yeah. 649 00:43:57,580 --> 00:43:59,340 - Barely a month later, 650 00:43:59,340 --> 00:44:02,220 there's a global medical conference in Seattle. 651 00:44:04,100 --> 00:44:07,420 The promise of the initial phase 3 trial results 652 00:44:07,420 --> 00:44:08,980 is now sinking in. 653 00:44:10,940 --> 00:44:14,900 Across the different ages and locations of children in the trial, 654 00:44:14,900 --> 00:44:17,900 around a year after they were first vaccinated, 655 00:44:17,900 --> 00:44:21,620 R21 has reduced cases of clinical malaria 656 00:44:21,620 --> 00:44:24,420 by about 70% to 80%. 657 00:44:24,420 --> 00:44:26,260 - Hey! Good morning! 658 00:44:26,260 --> 00:44:27,340 - Wow! - How are you? 659 00:44:27,340 --> 00:44:32,700 - So the teams from Oxford, Tanzania, Kenya, Mali and Burkina Faso 660 00:44:32,700 --> 00:44:37,100 gather to prepare to present their data publicly for the first time. 661 00:44:38,260 --> 00:44:41,260 - These people are just extraordinary. They are leaders in their field. 662 00:44:41,260 --> 00:44:42,860 - Hello. 663 00:44:42,860 --> 00:44:44,620 How are you? 664 00:44:44,620 --> 00:44:49,220 - The results that have come in show safety looks absolutely fine 665 00:44:49,220 --> 00:44:51,580 in literally thousands of children, 666 00:44:51,580 --> 00:44:54,540 and even more excitingly, the efficacy. 667 00:44:54,540 --> 00:44:56,540 The reaction was they cheered. 668 00:44:58,660 --> 00:45:02,980 - You know, seeing the numbers, that was a moment of excitement. 669 00:45:02,980 --> 00:45:05,540 Everybody was taken aback and said, 670 00:45:05,540 --> 00:45:08,740 "You know what? Wow, this is...this is real. 671 00:45:08,740 --> 00:45:10,220 "This is something." 672 00:45:11,620 --> 00:45:13,700 - When this result came out, 673 00:45:13,700 --> 00:45:19,380 I was like, "Ahh, oof, this is what I was waiting for long." 674 00:45:20,780 --> 00:45:23,220 - So here we are on Sunday. On Wednesday, 675 00:45:23,220 --> 00:45:26,180 we're going to try and tell the world about what we found. 676 00:45:29,220 --> 00:45:31,300 - If you'd asked me this morning, I would have said, 677 00:45:31,300 --> 00:45:33,060 "I'm filled with anxiety. 678 00:45:33,060 --> 00:45:36,540 "I have no idea how the rest of the scientific community 679 00:45:36,540 --> 00:45:38,300 "are going to take it." 680 00:45:38,300 --> 00:45:40,940 You know, people are going to critically analyse the results, 681 00:45:40,940 --> 00:45:44,460 that...that's what science is and that's what should be done. 682 00:45:44,460 --> 00:45:46,100 But having had the meeting today 683 00:45:46,100 --> 00:45:48,260 and, you know, the most important people 684 00:45:48,260 --> 00:45:50,020 who are part of the trial being there, 685 00:45:50,020 --> 00:45:54,300 the PIs of every site and just how excited they are, now I'm excited. 686 00:45:59,100 --> 00:46:02,980 We know our vaccine works. We know we have good data. 687 00:46:02,980 --> 00:46:05,380 I hope everyone is as excited as we are. 688 00:46:11,860 --> 00:46:15,740 - I'm very pleased today to be able to share with you the first data 689 00:46:15,740 --> 00:46:19,580 on the safety and efficacy of R21/Matrix-M, 690 00:46:19,580 --> 00:46:21,300 a new malaria vaccine. 691 00:46:22,860 --> 00:46:24,540 - This is a vaccine that works, 692 00:46:24,540 --> 00:46:28,340 that's going to be widely available at a reasonable price, 693 00:46:28,340 --> 00:46:31,340 and it could really, really make a big difference. 694 00:46:31,340 --> 00:46:34,340 It's trite to say game-changer, but I really think it is. 695 00:46:34,340 --> 00:46:37,340 - It's very encouraging news that they have the Serum Institute in Pune 696 00:46:37,340 --> 00:46:39,660 who's going to be able to really scale up 697 00:46:39,660 --> 00:46:42,020 the production of the vaccine. 698 00:46:42,020 --> 00:46:45,620 - For reducing the burden of disease and death in children, 699 00:46:45,620 --> 00:46:48,060 I mean, it's a wonderful result. 700 00:46:50,100 --> 00:46:51,140 - For the team, 701 00:46:51,140 --> 00:46:53,860 sharing their results is a moment to savour. 702 00:46:55,100 --> 00:46:58,740 R21 can't be directly compared with RTS,S - 703 00:46:58,740 --> 00:47:00,460 their trials were different - 704 00:47:00,460 --> 00:47:04,580 but there's now no doubt about this new vaccine's potential. 705 00:47:08,940 --> 00:47:13,940 Yet, for R21 to have any impact on the lives of children in Africa, 706 00:47:13,940 --> 00:47:17,580 all the data must be handed over for independent scrutiny 707 00:47:17,580 --> 00:47:19,700 by the World Health Organization. 708 00:47:29,420 --> 00:47:33,020 - There's never any time to sit back and enjoy the moment particularly. 709 00:47:33,020 --> 00:47:36,660 It's a relief, but back to the grindstone, really. 710 00:47:36,660 --> 00:47:39,780 The end of this week is submission to WHO, 711 00:47:39,780 --> 00:47:44,180 and so it's a massive dossier of safety and efficacy data 712 00:47:44,180 --> 00:47:49,140 that WHO will look at and decide whether that's enough data for them 713 00:47:49,140 --> 00:47:51,580 to approve the vaccine for widespread use. 714 00:47:52,580 --> 00:47:54,660 The key people at the Serum Institute are working 715 00:47:54,660 --> 00:47:58,620 on the submission package with us, so there's a lot going on. 716 00:48:00,900 --> 00:48:04,900 - The reason WHO assessment matters so much is stark. 717 00:48:06,340 --> 00:48:07,820 To purchase vaccines, 718 00:48:07,820 --> 00:48:11,500 African countries rely heavily on donated funds, 719 00:48:11,500 --> 00:48:15,780 and these won't be released without a WHO seal of approval. 720 00:48:17,020 --> 00:48:18,740 - If there's no money to distribute this vaccine, 721 00:48:18,740 --> 00:48:20,500 I mean, we can make the best vaccines in the world, 722 00:48:20,500 --> 00:48:22,980 but if nobody's going to buy it, nobody's going to distribute it, 723 00:48:22,980 --> 00:48:24,420 then it's all a waste of time. 724 00:48:24,420 --> 00:48:28,420 So, this is the next stage of the vaccine process. 725 00:48:30,260 --> 00:48:34,820 - But ahead of any WHO decision, in April 2023, 726 00:48:34,820 --> 00:48:36,700 there's surprise breaking news. 727 00:48:36,700 --> 00:48:42,180 - A day of pure elation for Ghana, for science and for all of humanity, 728 00:48:42,180 --> 00:48:45,180 as the FDA has granted approval to a new vaccine. 729 00:48:45,180 --> 00:48:47,780 - NEWSREADER: - Ghana's government has become the first in the world 730 00:48:47,780 --> 00:48:51,900 to clear the roll-out of malaria vaccine R21. 731 00:48:51,900 --> 00:48:55,460 - Ghana's drug regulator has reviewed the data on R21 732 00:48:55,460 --> 00:48:57,260 and approved it for use, 733 00:48:57,260 --> 00:49:01,140 signalling a clear and urgent demand for this new vaccine. 734 00:49:02,540 --> 00:49:07,420 Days later, Nigeria follows suit and Angola looks to place an order. 735 00:49:10,020 --> 00:49:14,300 But there's still no certainty that the WHO will approve the vaccine, 736 00:49:14,300 --> 00:49:16,980 and so unlock the necessary funds. 737 00:49:16,980 --> 00:49:21,140 - Let's get into the manufacturing details of how to scale up 738 00:49:21,140 --> 00:49:24,580 as soon as possible, because now I think there's a lot of excitement. 739 00:49:24,580 --> 00:49:29,620 - In Pune, Serum's CEO has a very big decision to make. 740 00:49:29,620 --> 00:49:32,780 - How many doses should we then make at risk? 741 00:49:32,780 --> 00:49:35,540 I was thinking around 20 million to 25 million doses. 742 00:49:35,540 --> 00:49:37,060 Do you think that would be OK? 743 00:49:37,060 --> 00:49:39,620 - That is... So 5 million, Angola wants, 744 00:49:39,620 --> 00:49:42,100 and Nigeria also want around 5 million, 10 million 745 00:49:42,100 --> 00:49:43,580 and Ghana around 5 million, 10 million. 746 00:49:43,580 --> 00:49:45,180 So 20 million, 25 million is good enough. 747 00:49:45,180 --> 00:49:47,500 - Well, should we make around 30 million to be safe? 748 00:49:47,500 --> 00:49:48,980 - I think so. We should try. 749 00:49:48,980 --> 00:49:50,420 - Fine. Go ahead, do it. 750 00:49:50,420 --> 00:49:54,420 Let me know what the costing and the risk we're taking in that is, 751 00:49:54,420 --> 00:49:56,060 but let's just go ahead. 752 00:49:56,060 --> 00:49:57,780 What's the expiry on that? 753 00:49:57,780 --> 00:49:59,740 - The expiry is about 18 months. 754 00:49:59,740 --> 00:50:01,620 - Yeah, that's a matter of concern. 755 00:50:03,180 --> 00:50:07,700 - Adar Poonawalla has just risked over $100 million 756 00:50:07,700 --> 00:50:11,820 to start production of 30 million doses of R21. 757 00:50:15,620 --> 00:50:19,780 They'll be offered at the very low price of under $4 a dose. 758 00:50:22,340 --> 00:50:26,020 The gamble is whether WHO approval and sales 759 00:50:26,020 --> 00:50:29,220 will come before the vaccine stockpile expires. 760 00:50:33,740 --> 00:50:36,180 - We've taken all the risk, you know, for the trials, 761 00:50:36,180 --> 00:50:38,820 for manufacturing the 30 million doses. 762 00:50:38,820 --> 00:50:41,860 We just hope that it's all worth it. 763 00:50:41,860 --> 00:50:43,540 I wouldn't have the freedom 764 00:50:43,540 --> 00:50:46,620 to make these sort of risky decisions and bets 765 00:50:46,620 --> 00:50:49,740 had I been accountable to multiple stakeholders, 766 00:50:49,740 --> 00:50:51,540 shareholders, banks, etc. 767 00:50:51,540 --> 00:50:54,260 Here, it's just a few people coming together 768 00:50:54,260 --> 00:50:57,220 and quickly deciding to go ahead on something. 769 00:50:57,220 --> 00:51:00,660 Everything is now on WHO to approve the vaccine. 770 00:51:00,660 --> 00:51:03,500 That's all we're waiting for, and then we can roll it out. 771 00:51:04,660 --> 00:51:09,980 - In Serum's cold storage, the shelves rapidly begin to fill with R21. 772 00:51:09,980 --> 00:51:11,580 - This is our R21 storage vault. 773 00:51:13,220 --> 00:51:16,340 This is a place where your heart fills with a joy 774 00:51:16,340 --> 00:51:21,380 because finally, the product which will get into the humans is ready. 775 00:51:21,380 --> 00:51:25,100 This entire cold room can accommodate 40 million doses, 776 00:51:25,100 --> 00:51:27,980 which means 10 million children's vaccination. 777 00:51:29,100 --> 00:51:30,260 Amazing feeling. 778 00:51:35,780 --> 00:51:40,940 - As R21 sits in storage, all the team can do now is wait. 779 00:51:43,660 --> 00:51:47,740 Even in Ghana and Nigeria, where the vaccine is already approved, 780 00:51:47,740 --> 00:51:50,020 no-one's come forward to pay. 781 00:51:50,020 --> 00:51:54,100 So across Africa, everything rests on the WHO decision. 782 00:51:55,780 --> 00:51:57,180 - There's a lot of anticipation. 783 00:51:57,180 --> 00:52:00,420 And, you know, it's the difference between thinking that, you know, 784 00:52:00,420 --> 00:52:02,220 maybe this vaccine will get rolled out next year. 785 00:52:02,220 --> 00:52:04,900 And, you know, those kids will start getting the benefit of the vaccine, 786 00:52:04,900 --> 00:52:07,740 or we might have another four years of clinical trials. 787 00:52:10,260 --> 00:52:12,820 It's the first part, I think, in this whole process 788 00:52:12,820 --> 00:52:15,220 where I felt really sort of out of control of what's happening, 789 00:52:15,220 --> 00:52:16,660 and it's quite an odd sensation 790 00:52:16,660 --> 00:52:18,540 when, you know, you've created something 791 00:52:18,540 --> 00:52:21,220 and then you just have to kind of release it out there 792 00:52:21,220 --> 00:52:25,180 into the wider world and see what everybody else makes of it. 793 00:52:29,980 --> 00:52:32,660 - Due process has to be followed. 794 00:52:32,660 --> 00:52:35,540 What's happening is that there's a balance being struck 795 00:52:35,540 --> 00:52:39,140 between having long enough follow-up in thousands of children 796 00:52:39,140 --> 00:52:43,020 to be really sure that there's no safety issue, 797 00:52:43,020 --> 00:52:46,780 and balancing that against the fact that a thousand children are dying 798 00:52:46,780 --> 00:52:50,780 from malaria every day, who could be vaccinated 799 00:52:50,780 --> 00:52:56,020 with a vaccine that is sitting in India waiting to be supplied. 800 00:52:56,020 --> 00:52:57,420 And that's tricky. 801 00:53:01,060 --> 00:53:02,300 We would like it right now. 802 00:53:02,300 --> 00:53:05,180 I mean, we would like it yesterday, if I may say so. 803 00:53:05,180 --> 00:53:08,020 I mean, I would love to have vaccines available 804 00:53:08,020 --> 00:53:12,140 for every single child in Africa who is at risk of getting malaria. 805 00:53:12,140 --> 00:53:16,660 This is my, er... This is my hope and my dream, really. 806 00:53:19,900 --> 00:53:24,540 We need to act fast, with urgency, because we know what is at stake. 807 00:53:25,820 --> 00:53:28,980 It would be a tragedy if we allow this vaccine 808 00:53:28,980 --> 00:53:31,140 to just be on the shelves. 809 00:53:31,140 --> 00:53:34,820 And therefore, my message to, you know, stakeholders 810 00:53:34,820 --> 00:53:39,220 and people making decisions about access to vaccine, 811 00:53:39,220 --> 00:53:40,900 I think they should remember that, 812 00:53:40,900 --> 00:53:42,860 you know, we don't have time to wait. 813 00:53:46,660 --> 00:53:50,740 - With just my scientist head on, I think there's no reason 814 00:53:50,740 --> 00:53:53,340 why this vaccine couldn't be approved for use. 815 00:53:54,340 --> 00:53:57,500 Do I think it will be approved for use? I don't know. 816 00:54:00,740 --> 00:54:03,980 - It's now a year since the Seattle conference. 817 00:54:05,580 --> 00:54:09,860 All that time, the team has been sharing continually updated evidence 818 00:54:09,860 --> 00:54:14,100 with the WHO that the vaccine is safe and cost-effective. 819 00:54:15,620 --> 00:54:20,100 And although R21's efficacy does decrease a little over time, 820 00:54:20,100 --> 00:54:22,500 a booster dose bumps it back up. 821 00:54:24,140 --> 00:54:25,180 But now... 822 00:54:25,180 --> 00:54:26,220 - Hello! 823 00:54:26,220 --> 00:54:28,660 - ..they've been told to expect an announcement. 824 00:54:30,340 --> 00:54:33,860 - Good morning, good afternoon and good evening. 825 00:54:33,860 --> 00:54:36,940 Today is a great day for health. 826 00:54:36,940 --> 00:54:39,260 A great day for vaccines. 827 00:54:39,260 --> 00:54:41,700 Almost exactly two years ago, 828 00:54:41,700 --> 00:54:44,500 WHO recommended the broad use 829 00:54:44,500 --> 00:54:49,700 of the world's first malaria vaccine called RTS,S. 830 00:54:49,700 --> 00:54:53,180 Today, it gives me great pleasure to announce 831 00:54:53,180 --> 00:54:59,140 that WHO is recommending a second vaccine called R21/Matrix-M, 832 00:54:59,140 --> 00:55:03,460 to prevent malaria in children at risk of the disease. 833 00:55:06,100 --> 00:55:09,300 - The WHO has approved R21 for use 834 00:55:09,300 --> 00:55:12,660 in any African child at risk of malaria... 835 00:55:14,220 --> 00:55:18,540 ..a decision that should trigger the release of critical donor funds, 836 00:55:18,540 --> 00:55:21,940 paving the way for vaccine roll-out in 2024. 837 00:55:23,780 --> 00:55:26,060 - Congratulations! What a great day! 838 00:55:26,060 --> 00:55:28,380 - Congratulations to you, too. 839 00:55:28,380 --> 00:55:32,260 This is an historic day for Africa, I think. 840 00:55:32,260 --> 00:55:34,580 - We're not talking about hundreds or thousands 841 00:55:34,580 --> 00:55:38,500 but, over time, well over a million lives saved 842 00:55:38,500 --> 00:55:43,820 is just staggering and hugely, hugely gratifying. 843 00:55:43,820 --> 00:55:46,580 And you just feel... 844 00:55:46,580 --> 00:55:47,620 Wow. 845 00:55:48,740 --> 00:55:52,540 - Really happy. Really relieved and, you know, 846 00:55:52,540 --> 00:55:54,540 proud that we've got here. 847 00:55:55,620 --> 00:55:58,740 You know, this opens the door for the next stage for the vaccine, 848 00:55:58,740 --> 00:56:01,060 which is to get out there into the real world. 849 00:56:01,060 --> 00:56:04,660 And that's the bit that I'm sort of most excited about, really. 850 00:56:07,460 --> 00:56:09,260 - I'm dreaming for that day to come, 851 00:56:09,260 --> 00:56:12,540 and I hope it will come sooner than later. 852 00:56:12,540 --> 00:56:14,060 And, er... 853 00:56:16,220 --> 00:56:17,700 Yeah, it's, er... 854 00:56:19,020 --> 00:56:21,540 Yeah, this is what... This is what I want to see, 855 00:56:21,540 --> 00:56:24,060 this is what every parent wants to see. 856 00:56:27,460 --> 00:56:32,940 - From 2024 onwards, the battle to beat malaria will be transformed. 857 00:56:34,340 --> 00:56:38,380 If funds are sustained to get R21 to all who need it, 858 00:56:38,380 --> 00:56:41,940 along with new, even better vaccines which may follow, 859 00:56:41,940 --> 00:56:44,340 this will indeed be game-changing. 860 00:56:46,060 --> 00:56:48,900 Beyond which the complete eradication of malaria 861 00:56:48,900 --> 00:56:52,860 may no longer simply be a hope, but become a reality. 862 00:56:54,020 --> 00:56:57,740 That will truly transform the lives and prospects 863 00:56:57,740 --> 00:57:01,260 of hundreds of millions of people across Africa. 864 00:57:01,260 --> 00:57:05,980 People like Zuhura Abbasi and her daughter, Farhiya. 865 00:57:25,700 --> 00:57:27,580 THEY SING TOGETHER