HSV-2 Vaccine
Prior efforts to develop HSV-2 vaccines have focused on the development of neutralizing antibodies that bind to proteins on the surface of the virus and prevent it from infecting host cells. In many cases, neutralizing antibodies are sufficient to prevent infection, but in the case of HSV-2, vaccine-induced neutralizing antibodies have failed to prevent infection in human trials despite promising results in small animal models. These failed vaccines have all been designed to promote neutralizing antibodies against the immunodominant glycoprotein D.
Our group adopted a highly novel strategy: we developed a version of HSV-2 in which gD is deleted from the viral genome. This virus is produced in a manner that allows it to undergo a single round of infection, but because the gD gene has been deleted, newly produced virions are unable to infect new cells. To our surprise, this virus induced high titers of antibody dependent cell cytotoxicity (ADCC)-inducing antibodies, and protected mice from challenges with even our most aggressive HSV-2 clinical isolates.
These observations prompted us to ask: what is it about gD that seemingly blocks the development of ADCC-inducing antibodies? Recently completed studies in our lab demonstrate that the Herpes Virus Entry Mediator (HVEM) protein is required for the generation of protective ADCC responses, and that gD interacts with HVEM to block not only the generation of ADCC-inducing antibodies, but also to block effector cell function.
Betsy C. Herold, M.D., delivered her lecture, "A Paradigm-Shifting Vaccine to Prevent and Treat Herpes Simplex Virus Infections" at the second annual Einstein-Montefiore Presidential Lecture.