amfAR, The Foundation for AIDS Research

HIV Research: Paving the Way to COVID Vaccines

By Rowena Johnston, Ph.D., and Jeffrey Laurence, M.D.

The speed by which the world’s scientific resources were mobilized to design, develop, manufacture and test current COVID-19 vaccines is unprecedented. The rapid development of the Pfizer and Moderna vaccines that are the mainstay of the U.S. vaccine program would not have been possible without innovative foundations developed through HIV vaccine research.

vax1Long-time amfAR grantee Dr. Drew Weissman developed a key technique leading to safer mRNA platforms for vaccines. Photo: Penn Medicine

All leading COVID-19 vaccine candidates to date, including Pfizer and Moderna, rely on their ability to stimulate production of antibodies and T cells targeted to a COVID-19 virus coat protein known as S, or “spike.”

S is required for the virus to infect a cell. But to ensure that a vaccine elicits an optimal response, its S protein component must be engineered to ensure that it is stabilized in the correct shape, or conformation. That process relies on insertion of an amino acid called proline into specific parts of S. This is a technique developed many years ago to create the best versions of HIV’s coat in the design of experimental AIDS vaccines.

Then there’s the technology behind delivery of the COVID-19 vaccine products themselves. For the Pfizer and Moderna vaccines, it starts with a genetic material, mRNA, encoding the optimized S protein. For over three decades, mRNAs have been tested as vaccine and therapeutic candidates, but with little success for two important reasons. First, when mRNA is delivered to cells, it induces a dangerous and potentially lethal immune response. To circumvent this problem, a technique for its modification was developed by Dr. Drew Weissman, a long-time amfAR grantee.

The extraordinarily rapid development of these COVID vaccines…was possible because the foundational work had already been done – by AIDS researchers.Once the mRNA is modified for safety, it must still be delivered to cells and the second challenge is that mRNA is very fragile. Without specialized lipid shells, known as nanoparticles or “fat bubbles,” to protect it from being rapidly dissolved in tissue, and to facilitate its entry into immune cells, there would be no mRNA COVID-19 vaccine. Among their earliest therapeutic applications, these lipid nanoparticles were used for the evaluation of this mRNA/lipid strategy to produce anti-HIV antibodies in mice.

The extraordinarily rapid development of these COVID vaccines, then, is neither fluke nor miracle. It was possible because the foundational work had already been done – by AIDS researchers. As The Wall Street Journal wrote in December 2020, “many of the new technologies and approaches employed to create potent Covid-19 vaccines and therapies trace their origins to the desperate search, starting in the early 1980s, to slow the spread of HIV.”

Dr. Johnston is amfAR vice president and director of research, and Dr. Laurence is senior scientific consultant.