Serum and Cervicovaginal Fluid Antibody Profiling in Herpes Simplex Virus (HSV) Seronegative Recipients of the HSV529 Vaccine

Author:

Wang, Kening

Dropulic, Lesia

Bozekowski, Joel

Pietz, Harlan L

Jegaskanda, Sinthujan

Dowdell, Kennichi

Vogel, Joshua S

Garabedian, Doreen

Oestreich, Makinna

Nguyen, Hanh

Ali, Mir A

Lumbard, Keith

Hunsberger, Sally

Reifert, Jack

Haynes, Winston A

Sawyer, Jaymie R

Shon, John C

Daugherty, Patrick S

Cohen, Jeffrey I
Author Address

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Serimmune, Santa Barbara, CA, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.,

Abstract:

Previous HSV2 vaccines have not prevented genital herpes. Concerns have been raised about the choice of antigen, the type of antibody induced by the vaccine, and whether antibody is present in the genital tract where infection occurs. We reported results of a trial of an HSV2 replication-defective vaccine, HSV529, that induced serum neutralizing antibody responses in 78% of HSV1 -/HSV2 - vaccine recipients. Here we show that HSV1 -/HSV2 - vaccine recipients developed antibodies to epitopes of several viral proteins; however, fewer antibody epitopes were detected in vaccine recipients compared with naturally infected persons. HSV529 induced antibodies that mediated HSV2-specific NK cell activation. Depletion of gD-binding antibody from sera reduced neutralizing titers by 62% and NK cell activation by 81%. HSV2 gD antibody was detected in cervicovaginal fluid at about one-third the level of that in serum. A vaccine that induces potent serum antibodies transported to the genital tract might reduce HSV genital infection. Published by Oxford University Press for the Infectious Diseases Society of America 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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Author Address