Dr. Alon Herschhorn is an Assistant Professor of Medicine in the Division of Infectious Diseases and International Medicine at the University of Minnesota. He has previously held a faculty position and conducted research at the Dana-Farber Cancer Institute and Harvard Medical School, and is the recipient of a Rothschild Fellowship and an amfAR Mathilde Krim Fellowship in Basic Biomedical Research. In 2019, Dr. Herschhorn won an Avenir Award for HIV/AIDS Research from the National Institutes of Health for a project investigating the pathways used by HIV to escape broadly neutralizing antibodies.
Dr. Alon HerschhornamfAR: We spoke last summer when you won the Avenir Award. How did your research progress in the months that followed?
Dr. Herschhorn: My research group is growing fast. Currently, we have four postdoctoral associates, two technicians, and two undergraduate students. We identified several HIV strains that are resistant to broadly neutralizing antibodies (bnAbs)—we study the mechanism of resistance. We also monitor the evolution of HIV-1 resistance to bnAbs by adaptation of HIV-1 to the presence of these antibodies.
Based on our previous studies, Dr. Ashley Haase and I recently formed a consortium of seven research groups that work together to bioengineer HIV immunogens—molecules that induce an immune response and are an integral component of vaccines. We received the Academic Investment Research Program (AIRP) award from the University of Minnesota Medical School and lead the efforts of our collaboration to develop new types of HIV vaccines.
amfAR: In response to COVID-19, you shifted your attention. How have you been applying your work in HIV research toward the novel coronavirus?
Dr. Herschhorn: For several years, I have been studying the function of HIV envelope glycoproteins (Env), which mediate HIV entry into cells. We developed molecular tools and obtained new insights into the mechanism of entry. Our most recently published study describes the unique Env function of a rare HIV-2 strain. Like HIV, SARS-CoV-2—the virus that causes COVID-19—displays viral Env that form a spike on the surface of the virus and mediate entry. The SARS-CoV-2 spike is the main target of neutralizing antibodies and the focus of vaccine development. With the COVID-19 outbreak and the urgent need for therapeutic and preventive interventions, it was only natural, as many other researchers have also done, to use our methods and experience to study the vulnerabilities of SARS-CoV-2 entry.
amfAR: Why do you think HIV researchers are often well positioned to work on COVID-19?
Dr. Herschhorn: Viruses share common strategies to replicate in target cells. They must enter a target cell by interacting with specific receptors on the cell surface and, once inside the cell, use the cellular machinery to produce viral proteins and nucleic acids for a generation of new progeny. The HIV-1 Env protein has been the focus of numerous investigations for more than 30 years, including several large-scale vaccine efficacy trials, and intensive structural, biochemical, biophysical, and bioinformatics studies. These efforts provided important insights and new tools for understanding the immune response, viral evolution and immune evasion, cross-species transmission, and more.
Like HIV-1 Env, the SARS-CoV-2 spike is composed of three protein subunits forming a trimer on the cell surface, has a role in transmission, and is the main target of neutralizing antibodies. Thus, tools developed for HIV research can be used to study the biology of SARS-CoV-2. For example, computational biologists are using tools developed for genetic analysis of HIV-1 Env to dissect the evolution of the SARS-CoV-2 spike. Structural biologists are using methods developed to express and purify HIV-1 Env trimer for the preparation of soluble SARS-CoV-2 spike to determine its structure.
amfAR: Are you optimistic about the prospects for an effective treatment or vaccine for COVID-19?
Dr. Herschhorn: Because of the global impact of the COVID-19 pandemic and the urgent need for interventions, multiple research directions and clinical trials have been initiated in the last few months. Some of these studies are now showing promising initial results. The antiviral drug remdesivir shortened the time to recovery of COVID-19 patients in the preliminary results of a clinical trial. mRNA-1273 vaccine elicited neutralizing antibodies against the SARS-CoV-2 spike in interim analysis of the Moderna vaccine trial. Now, we have to wait for the final reports and see how potential interventions can be optimized and integrated to provide maximum benefit to the general public.