Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection against herpes simplex virus 2

• Published in: PloS one 2013-06, Vol.8 (6), p.e65523-e65523
• Main Authors: Halford, William P, Geltz, Joshua, Gershburg, Edward
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Amino acids; Animals; Antibodies, Viral - immunology; Antibody response; Antigens; Antigens, Viral - immunology; Clinical trials; Correlation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Glycoproteins; Guinea Pigs; Herpes simplex; Herpes simplex virus; Herpes Simplex Virus Vaccines - immunology; Herpes viruses; Herpesvirus 2, Human - immunology; Hypotheses; IgG antibody; Immune response; Immune system; Immunity; Immunization; Immunoglobulin G; Immunoglobulin G - immunology; Immunology; Measles; Medical research; Medicine; Mice; Proteins; Proteomes; Studies; T cell receptors; Vaccination; Vaccines; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0065523

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.