An Interleukin 12 Adjuvanted Herpes Simplex Virus 2 DNA Vaccine Is More Protective Than a Glycoprotein D Subunit Vaccine in a High-Dose Murine Challenge Model

2017 ◽  
Vol 30 (3) ◽  
pp. 178-195 ◽  
Author(s):  
Kenneth C. Bagley ◽  
Jennifer A. Schwartz ◽  
Hanne Andersen ◽  
John H. Eldridge ◽  
Rong Xu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Vaccine ◽  
Subunit Vaccine ◽  
Interleukin 12 ◽  
High Dose ◽  
Glycoprotein D ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
D Subunit

scholarly journals Repertoire of Epitopes Recognized by Serum IgG from Humans Vaccinated with Herpes Simplex Virus 2 Glycoprotein D

2014 ◽  
Vol 88 (14) ◽  
pp. 7786-7795 ◽  
Author(s):  
J. Charles Whitbeck ◽  
Zhen-Yu Huang ◽  
Tina M. Cairns ◽  
John R. Gallagher ◽  
Huan Lou ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Subunit Vaccine ◽  
Humoral Response ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glycoprotein D ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Neutralizing Epitopes

ABSTRACTThe results of a clinical trial of a subunit vaccine against genital herpes were recently reported (R. B. Belshe, P. A. Leone, D. I. Bernstein, A. Wald, M. J. Levin, J. T. Stapleton, I. Gorfinkel, R. L. Morrow, M. G. Ewell, A. Stokes-Riner, G. Dubin, T. C. Heineman, J. M. Schulte, C. D. Deal, N. Engl. J. Med.366:34–43, 2012, doi:10.1056/NEJMoa1103151). The vaccine consisted of a soluble form of herpes simplex virus 2 (HSV-2) glycoprotein D (gD2) with adjuvant. The goal of the current study was to examine the composition of the humoral response to gD2 within a selected subset of vaccinated individuals. Serum samples from 30 vaccine recipients were selected based upon relative enzyme-linked immunosorbent assay (ELISA) titers against gD2; 10 samples had high titers, 10 had medium titers, and the remaining 10 had low ELISA titers. We employed a novel, biosensor-based monoclonal antibody (MAb)-blocking assay to determine whether gD2 vaccination elicited IgG responses against epitopes overlapping those of well-characterized MAbs. Importantly, IgGs from the majority of gD2-immunized subjects competed for gD binding with four antigenically distinct virus-neutralizing MAbs (MC2, MC5, MC23, and DL11). Screening of patient IgGs against overlapping peptides spanning the gD2 ectodomain revealed that about half of the samples contained antibodies against linear epitopes within the N and C termini of gD2. We found that the virus-neutralizing abilities of the 10 most potent samples correlated with overall gD-binding activity and to an even greater extent with the combined content of IgGs against the epitopes of MAbs MC2, MC5, MC23, and DL11. This suggests that optimal virus-neutralizing activity is achieved by strong and balanced responses to the four major discontinuous neutralizing epitopes of gD2.IMPORTANCESeveral herpes simplex virus 2 (HSV-2) subunit vaccine studies have been conducted in human subjects using a recombinant form of HSV-2 glycoprotein D (gD2). Although several distinct, well-characterized virus-neutralizing epitopes on gD2 are targeted by murine monoclonal antibodies, it is not known whether the same epitopes are targeted by the humoral response to gD2 in humans. We have developed a novel, biosensor-based competition assay to directly address this important question. Using this approach, we identified epitopes that elicit strong humoral responses in humans, as well as other epitopes that elicit much weaker responses. These data provide new insight into the human response to known neutralizing gD2 epitopes and reveal characteristics of this response that may guide future vaccine development.

scholarly journals Zinc Acetate/Carrageenan Gels Exhibit Potent ActivityIn Vivoagainst High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge

2011 ◽  
Vol 56 (1) ◽  
pp. 358-368 ◽  
Author(s):  
José A. Fernández-Romero ◽  
Ciby J. Abraham ◽  
Aixa Rodriguez ◽  
Larisa Kizima ◽  
Ninochka Jean-Pierre ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Zinc Acetate ◽  
Sexual Transmission ◽  
High Dose ◽  
Acetate Solution ◽  
Sexual Transmission Of Hiv ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACTTopical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard hasin vitroactivity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival;P< 0.001) against high-dose (106-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicityin vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosaein vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.

scholarly journals Meta-analysis of pregnancy outcomes in pooled randomized trials on a prophylactic adjuvanted glycoprotein D subunit herpes simplex virus vaccine

Vaccine ◽  
2013 ◽  
Vol 31 (13) ◽  
pp. 1759-1764 ◽  
Author(s):  
Fernanda Tavares ◽  
Brigitte Cheuvart ◽  
Thomas Heineman ◽  
Felix Arellano ◽  
Gary Dubin
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Vaccine ◽  
Pregnancy Outcomes ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Glycoprotein D ◽  
Simplex Virus ◽  
D Subunit

scholarly journals Herpes Simplex Virus DNA Vaccine Efficacy: Effect of Glycoprotein D Plasmid Constructs

2000 ◽  
Vol 182 (5) ◽  
pp. 1304-1310 ◽  
Author(s):  
J. E. Strasser ◽  
R. L. Arnold ◽  
C. Pachuk ◽  
T. J. Higgins ◽  
D. I. Bernstein
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Vaccine ◽  
Vaccine Efficacy ◽  
Glycoprotein D ◽  
Simplex Virus
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