Determining the Immunologic Profile of Primary HSV-1 Infections in Humans

Objectives: Herpes simplex virus 1 and 2 (HSV-1, HSV-2) traditionally cause oral and genital lesions respectively. However, HSV-1 is rapidly increasing in seroprevalence as a causative agent for genital infections. Despite many attempts to develop an HSV-2 vaccine, none have demonstrated sufficient protection, except one which showed moderate protection against HSV-1 infection. This has pushed the focus to understanding the immunology behind HSV-1 infection. In this study, our goal was to determine the serological immune profile to HSV-1 infection in humans.
Methods: Serum samples from HSV-1 positive individuals (n=20) with primary oral and genital infections were used. Entry assays determined the ability of serum antibodies to block virus entry into host cells and was used as a surrogate for neutralization. ELISA determined the relative amount of antibody against five HSV-1 entry glycoproteins (gD, gB, gC, gH/gL). Finally, high-throughput surface plasmon resonance imaging (SPRi) determined the epitope specificity of antibodies within the samples.
Results: Entry assays allowed the samples to be grouped based on their ability to neutralize virus (high, low, none). ELISA showed that each of the serum samples had relatively similar amounts of antibody to each glycoprotein, indicating that the difference in neutralization was not purely due to a difference in quantity of antibody. However, SPRi analysis showed major differences in the quality of epitopes targeted by the human. Generally, samples with better neutralization targeted a wider variety of epitopes compared to weaker neutralizers. Furthermore, high neutralizers tended to target characterized neutralizing epitopes, while sera that had low neutralization titers tended to target characterized non-neutralizing epitopes.
Conclusions: This study provides insight into the host response to primary oral and genital HSV-1 infection. Findings from this study will directly aid in the development of an HSV vaccine and have implications in the development of HSV-1 based oncolytic therapies.