Upcoming efficacy trial illustrates the value of African-led science

By Kundai Chinyenze

In February, I visited Maputo, Mozambique, for the first time.

I went there to attend an investigators meeting for PrEPVacc, a Phase IIb/III efficacy trial that will start later this year in Uganda, Tanzania, Mozambique, and South Africa. This trial will test two regimens of experimental DNA, poxvirus, and Env protein HIV vaccine candidates administered in combination with oral pre-exposure prophylaxis (PrEP) — the use of antiretrovirals to prevent HIV infection.

PrEPVacc’s design is novel. The trial aims to generate data on HIV vaccine efficacy, investigate correlates of protection, determine adherence to and acceptance of PrEP, and compare the efficacy of the experimental PrEP drug Descovy with Truvada, the only licensed PrEP drug.

This is the first trial designed to evaluate the efficacy of a vaccine candidate in the context of oral PrEP. PrEPVacc is also an African study. It is supported by European and American partners and funded by the European Union, but the trial database, trial management, and primary laboratory assays will be undertaken by African investigators.

Eugene Ruzagira, a senior scientist at the Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, is coordinating these efforts from Entebbe, Uganda. It is by no means the first trial to engage African researchers — there is a rich scientific history here, certainly in the HIV vaccine field — but it will be the first efficacy trial that will be coordinated and centrally managed by an African organization across four countries. Instead of gathering samples to ship off for analysis somewhere else, local investigators, who understand the local context and needs of the populations, will oversee this large and complicated HIV vaccine trial.

It has taken many years and much effort to get to this point. And it is just a hint of what is to come if we continue to engage with local investigators and develop their capacity to conduct more basic and clinical research on the African continent.

When the U.S. Agency for International Development (USAID) challenged us to launch a formal capacity-strengthening program at IAVI in 2014, it was both exciting and challenging. We set out to build the next generation of science leaders. We recruited early career researchers and aimed to develop independent, innovative investigators who are capable of addressing local and global public health issues, including contributing to HIV vaccine development and prevention research more broadly.

For the individual, this requires providing support to pursue advanced degrees, mentorship from senior scientists, and training in manuscript and grant writing so that they could fully develop the skills they need to succeed as independent researchers.

At the institutional level, it requires equipping local laboratories so that these investigators could conduct advanced science and clinical studies. This includes providing adequate funding, skilled labor, appropriate technology, as well as sufficient managerial and administrative capacity to plan, execute, monitor, and evaluate studies. Even in developed countries, amassing the resources required to undertake complex research endeavors is difficult. These difficulties are multiplied many times in sub-Saharan Africa.

Researchers starting their career paths here are now able to draw upon the extensive resources available at institutions such as the Kenya Medical Research Institute and KAVI Institute of Clinical Research in Kenya, the MRC/UVRI and LSHTM Uganda Research Unit, Projet San Francisco in Rwanda, and the Zambia Emory HIV Research Program. Two decades of hard work to develop the laboratory, clinical, and bioinformatic capabilities of these institutions are now enabling scientists to function independently and make significant contributions.

Regional labs are now able to perform immunology assays, including T-cell epitope mapping, B-cell assays, flow cytometry, multiplexing, and viral immunome profiling. There are still plenty of constraints on the research infrastructure on the continent, but human resources have improved significantly and the technology is more advanced.

To date, IAVI’s training programs have supported more than 42 advanced-degree candidates in HIV-related fields. Last year alone, 402 staff were trained in good clinical and good clinical laboratory practice. Scores of public health workers have received training and gained access to more advanced lab technologies. Hundreds of others are able to serve as frontline health care workers, having gone through regional trainings, including training in bioethics, mucosal sampling methods, long-acting reversible contraception services, and providing health services for key populations, such as men who have sex with men, female sex workers, and adolescent girls and young women.

Ten fellows have been accepted into IAVI’s post-doctoral training program, focusing on immunology and virology research. These mid- or early career scientists are now contributing to the basic scientific understanding of the viruses and immune responses in African populations, and are contributing to efforts to design vaccine immunogens. These post-doctoral scientists have published their research and in many cases have gone on to secure additional funding, including path-to-independence grants from SANTHE — a sub-Saharan network of African-led research in HIV/AIDS and tuberculosis—and highly competitive fellowships and grants from the Wellcome Trust and the U.S. National Institutes of Health.

They are able to do this because of the financial support, training, and mentorship they have received. Gloria Omosa-Manyoni, a lecturer in the University of Nairobi’s Department of Medical Microbiology, is one of these mentors. Omosa-Manyoni, who served as a principal investigator on an HIV vaccine trial, is one of several mentors in scientific writing, having trained at the University of California-San Francisco. She trains researchers on publishing their findings and how best to disseminate this information to other researchers and policymakers.

We recently held another course in scientific manuscript writing in Nairobi. Over time, this course and others like it will lead to more publications by African researchers. Of the number of peer-reviewed articles published with the help of IAVI’s partnership with USAID, some 62% in 2018 had lead authors based in Africa or India.

The numbers are encouraging, but the success of all of these capacity-strengthening efforts is best illustrated by the people, including Omosa-Manyoni and Ruzagira. It takes years of focused resources to mentor, train, and equip a capable scientist. Through sustained efforts — from international and local partners alike — we are starting to see more and more contributions to HIV vaccine research come from this part of the world, from laboratories that are organized and managed by investigators who live and work here. It’s been a long, sometimes difficult, and ultimately rewarding journey. One we must continue.

Kundai Chinyenze is senior medical director for IAVI based in Nairobi.

Originally published in IAVI Report, Vol. 23, No. 1, 2019.