Generating More Effective Vaccines Against Viruses

Research Brief

Generating More Effective Vaccines Against Viruses

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In 2017, Einstein’s William Jacobs, Jr., Ph.D., and Betsy Herold, M.D., reported developing an herpes simplex virus (HSV) vaccine, named ΔgD-2, from a strain of herpes simplex virus missing the glycoprotein D gene. The ΔgD-2 vaccine completely protected mice and guinea pigs from lethal infection with the viruses that cause genital and oral herpes. Rather than eliciting antibodies that neutralize the viruses themselves, this highly effective vaccine stimulates production of antibodies that mediate a powerful immune response called antibody-dependent cellular cytotoxicity (ADCC), in which antibodies bind to viral proteins that are trafficked to the surface of infected host cells. Immune cells then recognize these antibody-bound cells and promptly destroy them. ADCC has been shown to be a highly effective way of killing pathogen-infected cells as well as tumor cells.

In a study published online on August 24 in Proceedings of the National Academy of Sciences of the United States of America, Dr. Jacobs and colleagues report that eliciting antibodies that specifically mediate ADCC may offer better protection against influenza, for which effective vaccines are lacking. They cloned the gene for an influenza protein, hemagglutinin, into their ΔgD-2 vaccine, creating a vaccine they now called ΔgD-2: HAPR8. The new vaccine not only protected mice against otherwise lethal influenza challenges by eliciting ADCC-mediating antibodies, but it still worked effectively in preventing infection from lethal herpes virus challenges. Vaccines based on the ΔgD-2 vaccine platform could generate highly protective vaccines against a wide variety of viral pathogens, the researchers conclude.

Dr. Jacobs is the Leo and Julia Forchheimer Chair in Microbiology and Immunology and a professor of genetics and of microbiology & immunology at Einstein.