Nobel Prize for amfAR Grantee Dr. Drew Weissman

Leading HIV researcher Dr. Weissman and collaborator Dr. Katalin Karikó instrumental in development of mRNA Covid vaccines

Along with collaborator Dr. Katalin Karikó, veteran HIV vaccine researcher and amfAR grantee Dr. Drew Weissman of the University of Pennsylvania has been awarded the 2023 Nobel Prize in Physiology or Medicine for his work on messenger RNA (mRNA), which proved instrumental in the development of effective vaccines for Covid-19.

“We could not be more thrilled for Drs. Weissman and Karikó on this announcement from the Royal Swedish Academy of Sciences,” said amfAR CEO Kevin Robert Frost. “There is obviously no greater accolade than the Nobel Prize, and all of us at amfAR extend our heartfelt congratulations to both scientists on their lifesaving accomplishments and this richly deserved honor.”

For over three decades, mRNAs had 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. It is also very fragile. Drs. Weissman and Karikó figured out that by wrapping the mRNA in specialized lipid shells, known as nanoparticles or “fat bubbles,” they could protect it from being rapidly dissolved in tissue and facilitate its entry into immune cells.

Among its earliest therapeutic applications, the research was applied to the evaluation of this mRNA/lipid strategy to produce anti-HIV antibodies in mice. It subsequently attracted the attention of the drug companies Moderna and BioNTech, which would eventually use the technology as the foundation of their highly effective Covid-19 vaccines.

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. Weissman is currently a co-investigator on a multi-year amfAR funded research project aimed at developing and testing a complex gene therapy approach to curing HIV.

“As with so many seminal research advances, the scientific community was slow to appreciate the importance of the work of Drs. Weissman and Karikó,” said Dr. Jeffrey Laurence, amfAR Senior Scientific Consultant and a Professor at Weill Cornell Medical College. “Their work has transformed the field of vaccine research, and the world has seen in dramatic fashion the lifesaving potential of their achievements.”

Photos by Peggy Peterson/Courtesy Penn Medicine

Innovations editor Andrew McInnes put a few questions to Dr. Weissman about his work and the potential of mRNA vaccine technology.

How did you become interested in HIV?

I was a medical student and resident when HIV spread to the U.S. I went to the National Institute of Allergy and Infectious Diseases for my allergy/immunology fellowship and became interested in the immunopathogenesis research Tony Fauci was doing, so I joined his lab and started doing HIV research.

Can you tell us about your involvement in the amfAR-funded combination gene therapy study that’s currently underway?

I am one of the Principal Investigators on this project. We developed the modified mRNA-LNPs [lipid nanoparticles] that produce two broadly neutralizing monoclonal antibodies and mRNA-LNPs that target resting CD4 T cells and deliver an enzyme that cuts out the provirus.

Where are we in the process of developing mRNA vaccines against HIV?

Phase 1 clinical trials are in process and have shown positive results. I believe we will need five to seven more years of phase 1 trials before we have a vaccine that can be tested in Phase 3 trials.

Which diseases are mRNA vaccines most likely to be effective against?

Certainly diseases where infection is blocked by antibodies, but modified mRNA-LNP (lipid nanoparticle) vaccines also induce potent T-cell responses. They have also been effective in certain cancers. New suppressive vaccines for autoimmune diseases and food and environmental allergies are being developed.

What are the limits of mRNA vaccine technology?

I do not think we know yet.

Which do you think will come first: A vaccine for HIV? Or a cure?

Probably a cure, as macaque trials are ongoing and, as I said above, it will likely be five to seven years before we have a preventative vaccine that’s ready for Phase 3 clinical trials.

amfAR Grantees, 2023

HIV Research: Paving the Way to COVID Vaccines

Developing the Next Generation of COVID-19 Vaccines