title: Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine.
abstract: Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.
authors: Dept of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62702, United States of America.
authors: Joshua J
authors: JJ
authors: Geltz
authors: Dept of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62702, United States of America.
authors: Edward
authors: E
authors: Gershburg
authors: Dept of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62702, United States of America.
authors: William P
authors: WP
authors: Halford
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D006558:Herpes Genitalis / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000235:genetics* / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D022301:Herpes Simplex Virus Vaccines; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2