title: Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection against herpes simplex virus 2.
abstract: We lack a correlate of immunity to herpes simplex virus 2 (HSV-2) that may be used to differentiate whether a HSV-2 vaccine elicits robust or anemic protection against genital herpes. This gap in knowledge is often attributed to a failure to measure the correct component of the adaptive immune response to HSV-2. However, efforts to identify a correlate of immunity have focused on subunit vaccines that contain less than 3% of HSV-2's 40,000-amino-acid proteome. We were interested to determine if a correlate of immunity might be more readily identified if 1. animals were immunized with a polyvalent immunogen such as a live virus and/or 2. the magnitude of the vaccine-induced immune response was gauged in terms of the IgG antibody response to all of HSV-2's antigens (pan-HSV-2 IgG). Pre-challenge pan-HSV-2 IgG levels and protection against HSV-2 were compared in mice and/or guinea pigs immunized with a gD-2 subunit vaccine, wild-type HSV-2, or one of several attenuated HSV-2 ICP0 (-) viruses (0Δ254, 0Δ810, 0ΔRING, or 0ΔNLS). These six HSV-2 immunogens elicited a wide range of pan-HSV-2 IgG levels spanning an ∼500-fold range. For 5 of the 6 immunogens tested, pre-challenge levels of pan-HSV-2 IgG quantitatively correlated with reductions in HSV-2 challenge virus shedding and increased survival frequency following HSV-2 challenge. Collectively, the results suggest that pan-HSV-2 IgG levels may provide a simple and useful screening tool for evaluating the potential of a HSV-2 vaccine candidate to elicit protection against HSV-2 genital herpes.
authors.affiliation: Department of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America. halford@siumed.edu
authors.forename: William P
authors.initials: WP
authors.lastname: Halford
authors.forename: Joshua
authors.initials: J
authors.lastname: Geltz
authors.forename: Edward
authors.initials: E
authors.lastname: Gershburg
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006168:Guinea Pigs; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D022301:Herpes Simplex Virus Vaccines; D007074:Immunoglobulin G