RV144 and the future of an HIV vaccine

In 2001, I traveled to Ghana as a graduate student working on a US Agency for International Development-funded decentralization program. I arrived armed with materials on local governance best practices. But the mayors I met were focused on urgent public health issues: clean water, HIV/AIDS, tuberculosis, and malaria. That trip, meant to be an early lesson in governance, became my first and most personal education in global health. It also nearly killed me. I was taking mefloquine weekly to prevent malaria. Toward the end of our stay, my partner and I set off to explore the country. Somewhere along the way, I developed what I believed to be giardia. That infection likely compromised the absorption of the mefloquine and left me dangerously vulnerable. One night in the village of Kokrobite, I woke with a high fever and chills so intense I could barely stand. A local man saw me and immediately recognized it as malaria. He arranged for a taxi to take me back to Accra. Before I left, he handed me a small, crumpled packet labeled in Chinese characters. Inside was a blister pack of pills. The only word written in English on the package was artesunate. He told me it would help, and, in that moment, sick, scared, and weak, I took it. At the hospital, a blood smear confirmed that I had cerebral malaria caused by Plasmodium falciparum, the deadliest strain. Cerebral malaria can cause brain swelling, coma, and death. I drifted in and out of consciousness for days. At one point, hospital staff told my partner that there was nothing more they could do. I should “go home” and be “as comfortable as possible.”My partner worked relentlessly to get me on one of the next flights back to the United States. I was so sick that the airline nearly refused to let me board. Once we arrived home, I was seen right away by an infectious disease doctor at Johns Hopkins Hospital. After reviewing my labs and the herbal remedy package, he said plainly: this saved your life. The artesunate had bought me enough time to survive the journey and begin treatment. At the time, the World Health Organization had not yet formally endorsed artemisinin-based combination therapies (ACTs) as the global standard for P. falciparum malaria. That came in 2006. But the effectiveness of artesunate alone was already well known in many parts of the world. That medicine saved my life.I missed several weeks of school but made a full recovery. Without that drug and the help of my partner (now my husband) and friends in Accra, I wouldn’t be here today. More than two decades have passed, and we've made tremendous progress. Insecticide-treated bed nets, rapid diagnostic tests, and ACTs have saved millions of lives. Two malaria vaccines, RTS,S and R21/Matrix-M, have been approved. Long-acting monoclonal antibodies are showing promise as seasonal protection for children. Newer insecticide-treated nets help counter resistance. And researchers are exploring RNA-based therapeutics and single-dose cures.Many of these breakthroughs are being developed by members of the Global Health Technologies Coalition, where I now serve as Executive Director. These tools represent our best chance not just to control malaria but to end it.But progress is not guaranteed. Cuts to foreign assistance and global health research and development are already slowing the progress of innovations in the pipeline. Some promising tools may be delayed or abandoned. That means more children at risk, more untreated infections, and more drug-resistant strains emerging. The parasite has evolved before. It will do so again if we let it. And malaria is no longer a disease that happens mostly outside of the United States. In the past two years, locally acquired cases have been reported in Florida, Texas, and Maryland. Climate change, global travel, and changing mosquito habitats are making malaria a threat we can no longer treat as distant. I know how thin the line is between surviving this disease and not. For me, it’s not abstract. It’s the memory of a fevered body, the generosity of strangers, and a medicine in the right place at the right time. This World Malaria Day, I urge leaders and policymakers to stay the course. The science is moving forward. But science alone isn’t enough. If we don’t finish what we’ve started, we risk letting malaria surge back and take more lives with it. Science has given us the tools. The question now is whether we will act in time or let the disease outpace us once again. 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. The Sabin Vaccine Institute has launched a multi-site Phase 2 clinical trial, supported by the Biomedical Advanced Research and Development Authority, in the United States to test its Marburg vaccine candidate, as outbreaks of the virus, for which there is no approved vaccine, grow in frequency. This trial builds on previous Phase 2 testing in Kenya and Uganda, as well as an open-label Phase 2 trial in Rwanda during the country’s outbreak last year. These trials in the African regions where Marburg and other similar viruses are most common or endemic are key to ensuring the vaccine is effective in the populations currently facing the highest risk of outbreaks. In addition, this new trial in the United States provides key safety and immune response data in non-endemic populations, helping prepare us for the possibility of outbreaks outside of the virus's typical range.Researchers have discovered a small antibody fragment that can block fertilization by targeting a key protein on the egg's surface, potentially paving the way for a nonhormonal contraceptive method. The fragment was found to be effective in mice, and it could potentially have fewer side effects due to its small size. Currently available hormonal contraceptive methods can cause side effects, like mood changes, headaches, or increased risk of blood clots, leading researchers to look for nonhormonal options for people who do not want to or cannot use hormonal methods. The researchers will next develop a similar antibody for human targets and test it in IVF experiments.The Drugs for Neglected Diseases initiative (DNDi) and partners initiated Phase 2 clinical trials in Malawi and Tanzania testing a new, easier-to-administer, and patient-friendly formulation of flucytosine, a medicine used to treat cryptococcal meningitis, which is a major health threat to people with weakened immune systems, including those with advanced HIV disease. Currently, flucytosine can be difficult to administer in resource-limited settings, and many countries face limited supply. As a result, access to timely treatment is limited in Africa, where the disease kills up to 70 percent of those who get it. The new formulation reduces dosing frequency from four times a day to just twice daily, is easier to take with water or through a nasogastric tube, and is suitable for outpatient self-administration.