Dr. Susan Zolla-Pazner is a professor in the departments of Medicine and Microbiology at the Icahn School of Medicine at Mount Sinai and a guest investigator at the Rockefeller University. Her work has been pivotal in establishing the central role of antibodies in protection from HIV infection and thereby helping to focus the efforts of the HIV vaccine field on humoral immunity as a preventive approach, leading the American Association for the Advancement of Science to refer to her as an “antibody person.” Named one of “Six Prominent Women Scientists Making a Difference in the AIDS Fight” (IAVIReport), she has discussed her vaccine-development work on PBS’s “Charlie Rose” show.
Building on her decades of research into the antigenic and structural nature of the second and third variable region (V2 and V3) of the HIV envelope glycoprotein, gp120, Dr. Zolla-Pazner measured the levels of antibodies (Abs) specific for these regions in the vaccine and placebo recipients of the RV144 clinical vaccine trial in Thailand. These were 2 of more than 100 assays run by scientists around the globe to determine if there was an immune correlate of the reduced rate of HIV infection in the vaccine recipients. Independent statistical analyses of the data indicated that the only independent correlate of reduced infection was the level of V2 Abs in the sera of vaccine recipients. These results indicated that, as Dr. Zolla-Pazner had hypothesized more than 10 years before, Abs to variable regions of gp120 play a crucial role in protection from infection. In addition, Dr. Zolla-Pazner measure Ab levels to several additional sites on gp120 at various times after the end of the immunization protocol of the trial. She showed that Abs reached maximal levels 2 weeks after the last immunization and dropped to background levels 6 months later. These findings corresponded with data showing that maximum protection from infection occurred in the first 6 months after the immunization period, and that there would be little if any protection thereafter. Together, these results strongly suggested that antibodies were a key to protection from HIV infection, a highly controversial point until the findings of the Zolla-Pazner lab.
Dr. Zolla-Pazner and her colleagues have spent the last 10 years developing “designer vaccines,” i. e., V2- and V3-scaffold proteins that focus Ab production on these regions of gp120. Her studies in rabbits and nonhuman primates have demonstrated that structure-based recombinant vaccines induce Abs that react with the envelopes of viruses from diverse HIV subgroups and have biologic activity, including neutralization and phagocytosis.