Herpes Simplex Virus 1 and 2 Vaccine Design: What can we Learn from the Past?

Abstract

This chapter is devoted to the topics of not yet marketed HSV vaccine, which is still in the focus of interest, especially from the point of immunotherapeutic use. To understand the principles of vaccination strategies (prophylactic and/or immunotherapeutic), the pathogenesis of herpes simplex virus 1 (HSV-1) and/or HSV-2 infections in animal models is briefly outlined. Even when both herpesviruses may spread via bloodstream, which is especially true in the immunocompromised host, the main route of their transmission is along peripheral nerves. Both viruses establish latency in ganglion cells, and after reactivation, they spread along axons back to the site of primary infection. Since neither the establishment of latency nor its reactivation can be fully controlled by virus-neutralizing antibodies, the outcome of immune response greatly depends on the activity of cytotoxic CD8+ T lymphocytes. The majority of important antigenic epitopes is located in envelope glycoproteins (such as gB, gD, gE, gC and gG) that are related to virus adsorption and penetration into susceptible cells. The HSV-1 and/or HSV-2 experimental vaccines designed so far were either purified virion products derived from infected cells (subunit vaccines), purified recombinant immunogenic herpes simplex virus HSV-coded proteins (especially gD), and/or attenuated live viruses lacking some of virulence tools (such as gH and/or gE). We bring a comprehensive overview of the efficacy of experimental HSV-1/HSV-2 vaccines and discuss our own data. In conclusion, we believe in the continued demand of HSV-1 and HSV-2 vaccines, at least for their immunotherapeutic use, suggesting unified evaluation criteria for clinical trials to reach consent at their interpretation.

Peptide Vaccines: New Trends for Avoiding the Autoimmune Response

“…Moreover, the vaccine in question has significantly reduced the HSV-1 shedding as detected in tears, and boosted the number and function of HSV-1 gD epitope-specific CD8+ T cells in the draining lymph nodes, conjunctival sac and trigeminal ganglion [81]. In comparison to the successful HSV-2 and/or HSV-1 derived experimental vaccines [82], which were mainly semipurified infected cell components and/or recombinant immunogenic polypeptides (especially gD and/or gH), the above mentioned recent attempts aiming to prepare selected oligopeptide (epitope) mixes as future vaccines seem promising as well. The safety, immunogenicity and protective efficacy of a laser adjuvant peptide vaccine (LAP vaccine) were tested in the B6 mouse as a model of genital herpes.…”