Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

Frank Wegmann,Thorunn A Olafsdottir,Josefine Persson,Yuan Zhang,Gary H Cohen,Tina M Cairns,Quentin J Sattentau,Karolina Thörn,Ali M Harandi,Roselyn J Eisenberg

doi:10.3389/fimmu.2016.00640

Frank Wegmann, Thorunn A Olafsdottir + Show 8 more

Open Access

https://doi.org/10.3389/fimmu.2016.00640

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Abstract

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

Highlights

HSV-2 is the leading cause of genital herpes, one of the most prevalent sexually transmitted infections [1]
We showed that nasal immunization confers protective immunity to primary genital herpes, establishment of latency, and recurrent outbreaks in guinea pigs
The guinea pigs immunized ml. (C) Disease progression during latent HSV-2 infection shown as mean cumulative disease score over time (n = 7–18). (D) RNA extracted from ganglia (n = 6–17) was quantified by real-time PCR with primers specific for HSV-2 latencyassociated transcript (LAT)

Summary

Introduction

HSV-2 is the leading cause of genital herpes, one of the most prevalent sexually transmitted infections [1]. HSV-2 enters via the epithelium of the genital tract mucosa, where it replicates, and transfers to the sensory neurons innervating the infected area. The virus establishes life-long latency in the dorsal root ganglia (DRG), where it can sporadically reactivate and cause recurrent genital herpes disease [2]. Re-infection of epithelial cells during recurrent outbreaks may lead to symptomatic or asymptomatic HSV-2 shedding [3]. During the silent latent phase of HSV infection the latencyassociated transcript (LAT) is the only RNA transcribed and is used as a latency marker [4].

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