Sci. Immunol. 4, eaaw7083 (2019)

Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted pathogen that establishes lifelong infection with recurrent episodic genetic lesions and subclinical viral shedding. Although antibody responses can control HSV-2, so far no effective vaccine against this virus has been developed. In Science Immunology, Awasthi et al. describe a preclinical study testing the efficacy of trivalent protein or mRNA vaccine formulations designed to neutralize HSV-2 and prevent subclinical viral replication and shedding. Both vaccine formulations target viral glycoproteins gC2, gD2 and gE2, which are responsible for viral entry and immunoevasion. Both vaccines also elicit neutralizing antibody responses to HSV-2 as well as to HSV-1. While the trivalent protein-subunit vaccine against HSV-2 provides partial protection to infected mouse and guinea pigs, lipid nanoparticles containing modified mRNAs (mRNA-LNPs) encoding the viral glycoproteins give superior protection against intravaginal viral challenge, prevent HSV-2 replication in dorsal root ganglion cells and block viral shedding. These findings offer hope for the development of effective mRNA-LNP vaccines for humans.