Development Of Vaccines For Genital Herpes Simplex Infection

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Herpes simplex virus 2 (HSV-2) causes genital herpes and increases the risk of transmission and infection with HIV. Thus a vaccine for HSV-2 would not only reduce the rate of genital herpes, but also might reduce spread of HIV. Several HSV-2 vaccines have been tested in humans for prevention or reduction of genital herpes disease, but none has been licensed for use in humans. We performed a randomized, double blind, placebo-controlled clinical trial of a replication-defective vaccine for HSV2 termed HSV529. This vaccine can infect cells, but not replicate in the cells. We vaccinated three groups of 20 subjects with three doses (at 0, 1, and 6 months) of HSV529 (15 subjects per group) or saline placebo injection (5 subjects per group). The groups were a) subjects who were infected with HSV2 in the past but may or may not have been infected with HSV-1 (HSV1+/-/HSV2+), (b) subjects who were infected only with HSV1 (HSV1+/HSV2-), and (c) subjects who were not infected with HSV1 or HSV2 (HSV1-/HSV2-). Each subject was followed after vaccination, and safety, the primary endpoint, and immune responses to the vaccine were studied. Seventy-eight percent of HSV1-/HSV2- vaccine recipients had > 4-fold rises in neutralizing antibody titer after three doses of vaccine, whereas none of the participants in the other serogroups had such responses. Unlike subunit vaccines for HSV2 that only induce antibodies to one or a few HSV-2 proteins, the HSV529 vaccine is expected to produce antibodies to most of the HSV2 proteins in vaccine recipients. In FY2022 we analyzed the innate immune response in persons receiving the HSV529 replication defective vaccine and found a number of changes in gene expression at the RNA level that were different in men versus women, and different in persons previously infected with HSV versus those that had never been infected. A manuscript reporting these differences is under review.