Preventing Neonatal Herpes: Protection after Maternal Mrna-Lipid Nanoparticle Vaccination Equals or Exceeds That from Prior Maternal Genital Infection in Murine Models

Abstract Neonates are vulnerable to poor outcomes from herpes simplex virus (HSV), but maternal infection eliciting non-sterilizing immunity prior to delivery provides some protection. We are therefore pursuing birthing parent vaccination with nucleoside-modified mRNA-lipid nanoparticles (mRNA-LNPs) to prevent neonatal herpes. Our trivalent vaccine encodes HSV type 2 (HSV-2) proteins involved in attachment and immune evasion (gC2, gD2, and gE2). We have shown that this vaccine protects against genital HSV and neonatal HSV-2 in mice. Here, we tested how well murine dam vaccination prior to pregnancy protects pups against HSV type 1 (HSV-1) challenge compared to prior maternal intravaginal HSV-1 infection. Dams were immunized intramuscularly with the HSV-2 trivalent mRNA-LNP vaccine or a control immunogen (PolyC RNA-LNP), or were infected intravaginally with HSV-1 (HSV-1 ivag). Pups were challenged intranasally with HSV-1 on the 3rd day of life. Pups born to dams previously immunized or infected survived through 28 days (mRNA 95% vs. HSV-1 ivag 96%, N.S.; vs. PolyC 13%, p<0.0001). Likewise, they were protected from HSV-1 dissemination to the brain, lung, liver, spleen, and kidney by plaque assay (mRNA 2/45 organs affected vs. HSV-1 ivag 6/20, p=0.0083; vs. PolyC 69/80, p<0.0001). Additionally, fewer organs showed necrosis by histopathology of brain, lung, and liver, though not statistically significant, and fewer mRNA and HSV-1 ivag pups had detectable HSV-1 DNA in the trigeminal ganglia by qPCR (mRNA 6/30 vs. HSV-1 ivag 7/26, N.S.; vs. PolyC 17/18, p<0.0001). These studies demonstrate that the mRNA vaccine provides comparable to improved protection against neonatal HSV-1 challenge versus prior maternal HSV-1 intravaginal infection. AD was supported by NIH NIAID T32 AI118684. HMF, SA, GHC, and DW were supported by NIH NIAID R01 AI139618 and an unrestricted grant from BioNTech SE. KPE was supported by NIH T32 NS007180. The funders had no input or influence on the content of this abstract.