Pew Biomedical Scholar Seeks to Develop 'Universal Vaccine' for HIV

Each year, millions of Americans travel to their doctors’ offices and local clinics to get vaccinated against dangerous, and potentially deadly, viruses. That’s because viruses rapidly mutate and learn to evade the immune system, and scientists must update vaccines seasonally to make sure people are protected against evolving strains.

But some researchers envision a different solution: a “universal vaccine” that could protect against multiple viral strains and offer a more long-lasting public health solution.

Courtesy of Subject

Dr. Amelia Escolano, a 2022 Pew biomedical scholar from The Wistar Institute, is investigating novel vaccination approaches against HIV-1, which currently has no available vaccine. She is using cutting-edge techniques to trace how antibodies evolve in response to vaccination protocols that involve repeated exposure to viral antigens. Through this work, Escolano’s lab hopes to develop a universal vaccine for HIV and, in turn, pioneer new ways to protect against rapidly mutating viruses. 

This interview with Escolano has been edited for clarity and length. 

Q. What’s a “universal vaccine”?

A. In the context of HIV, a universal vaccine would protect against a large range of viral variants—or different mutated versions of a specific virus. For example, we know that there are hundreds of HIV variants in circulation. A universal vaccine could grant protection against all those variants, or at least a large majority. The same concept could apply to SARS-CoV-2 or influenza, neither of which currently has a universal vaccine.

Q. Are there any universal vaccines on the market today?

A. Not yet. We receive seasonal boosters for influenza and SARS-CoV-2 to fight new variants. Ideally, a universal vaccine would not only confer protection against variants that are currently in circulation, but also against potential future ones.

Q. Is this where your research comes in?

A. Yes. We’re working to develop a vaccine that induces antibodies that can protect against a large majority of HIV variants. Antibodies are proteins produced by the immune system to fight off harmful pathogens by binding to specific components of the pathogen called antigens. Inducing antibodies that can broadly protect against HIV is a complex task. We need to design a vaccine that induces antibodies that target regions of the virus known as epitopes that are common across all the different HIV variants. My laboratory is working to design vaccine protocols that induce antibodies that target several of these epitopes.

Q. Where did this approach come from?

A. As a postdoctoral fellow, I developed a novel form of vaccination called sequential immunization, which involves multiple immunizations with slightly different viral antigens. Our preclinical studies showed that sequential immunization could induce antibodies with the ability to target one of the common epitopes of HIV, and thus broadly neutralize multiple HIV variants. This brought a lot of hope to the field because it was the first time that we knew these types of antibodies could be induced by vaccination.

Q. How did this early discovery inform your current work?

A. My lab is continuing to work with sequential immunization. With Pew’s support, we’ve developed a cool technology that allows us to track B cells, the specialized cells that produce antibodies, and see how those cells behave when we vaccinate using sequential immunization.

Q. What’s the value of tracking and labeling B cells?

A. This novel method will help us investigate the immune response to vaccination. For example, we can label B cells in a way that lets us know how each round of the sequential immunization is impacting the cells in terms of their function as mediators of the immune response. We can also investigate where these B cells are located at different time points during the vaccination protocol. Interestingly, our new technology can be adapted to investigate responses to vaccination against different pathogens, against infection, or even in cancer.

Q. Where does a potential vaccine fit in with other HIV prevention methods?

A. There’s a debate in the field about whether drug advancement will reduce the priority for developing a vaccine. Recent results using a drug called lenacapavir are very promising and suggest that treatments may be able to confer protection for long periods of time. Ultimately, an efficacious vaccine could confer protection for a very long time, and it would be the cheapest approach, which would enable broader accessibility. Designing a vaccine that universally protects against HIV is challenging. Different geographical regions have different predominant circulating variants. More achievable vaccines, adapted to different geographical regions, could be developed to specifically target the fewer predominant variants.

Q. Are there any common misunderstandings about your work?

A. When discussing my work, some people have expressed concerns about the possibility of getting infected with HIV if they are vaccinated. However, the type of vaccine we are working on could never result in infection. To induce antibodies that can fight HIV, we inject only a small component of the virus, not the virus itself. There is absolutely no risk of being infected. The same is true for SARS-CoV-2 and influenza vaccinations. There is a lot of misinformation regarding vaccines in general.

Q. What’s your end goal with this research?

A. Currently, sequential immunization is being evaluated in clinical trials by different groups. My lab is finalizing very promising preclinical studies with our vaccine candidate, which we believe could accelerate the development of neutralizing antibodies against HIV. These studies are being carried out in preparation for a human clinical trial. Seeing how my research has evolved from in vitro tests to preclinical animal models and a clinical trial on the horizon is so exciting. I am happy that my lab can do this, and my lab would be the happiest if we someday see one of our vaccines being used for humans. But ultimately, I want to be able to contribute knowledge to the scientific community so that we can learn how to design better vaccines for future viruses or bacteria.