Vaccine strategy for Herpes simplex viruses 1 and 2: trivalent VLP vaccine for HSV-2 in HSV-1 amplicon vector

Abstract

Herpes simplex virus (HSV), type 1 (HSV-1) and type 2 (HSV-2), co-evolved with humans and is present in high frequency in the general population, affecting approximately 190 million people worldwide. In general, with a mild or asymptomatic manifestation, it can cause serious neonatal infections, developing encephalitis and keratitis. Furthermore, neuroinflammation/immunosenescence with the reactivation of HSV-1 can trigger senile dementia and/or Alzheimer's disease. Therefore, it is imperative to develop vaccine bases in order to prevent primary infection or complications from HSV reactivation. Currently, a trivalent vaccine against HSV-2, based on RNA vaccines, is in clinical trials for HSV-2 glycoprotein C, D and E targets. Our proposal is to develop a trivalent vaccine for HSV-2, using the virus-like-particle (VLP) platform to express the gD2/gC2/gE2 genes, in a defective HSV-1 viral vector. Due to the fact that we use an HSV-1 VLP, with all the structural components of the wild-type viral particle (except its genome), we will also evaluate the immunoprotection of the vaccine system against HSV-1. This HSV-1 amplicon vector is already constructed. The effectiveness of the vaccine will be evaluated in immunization protocols to analyze: i) vaccine response in a genital infection model and neuronal reactivation in adult mice, ii) maternal vaccination to evaluate offspring protection, and iii) duration of the vaccine response, in lactating mice to adulthood. The parameters to be analyzed to assess the effectiveness of the vaccine include: animal imaging, antibody production, follicular T cells, cytotoxic T cells, antiviral cytokines and transcriptional profile of antiviral factors. This vaccine proposal for both HSV-1 and 2 aims to protect against genital herpes infection, reduce the likelihood of viral transmission during childbirth and neonatal infection, in addition to providing the greatest benefit to public health.