An HSV-2 nucleoside-modified mRNA genital herpes vaccine containing glycoproteins gC, gD, and gE protects mice against HSV-1 genital lesions and latent infection

Abstract

HSV-1 causes 50% of first-time genital herpes infections in resource-rich countries and affects 190 million people worldwide. A prophylactic herpes vaccine is needed to protect against genital infections by both HSV-1 and HSV-2. Previously our laboratory developed a trivalent vaccine that targets glycoproteins C, D, and E present on the HSV-2 virion. We reported that this vaccine protects animals from genital disease and recurrent virus shedding following lethal HSV-2 challenge. Importantly the vaccine also generates cross-reactive antibodies that neutralize HSV-1, suggesting it may provide protection against HSV-1 infection. Here we compared the efficacy of this vaccine delivered as protein or nucleoside-modified mRNA immunogens against vaginal HSV-1 infection in mice. Both the protein and mRNA vaccines protected mice from HSV-1 disease; however, the mRNA vaccine provided better protection as measured by lower vaginal virus titers post-infection. In a second experiment, we compared protection provided by the mRNA vaccine against intravaginal challenge with HSV-1 or HSV-2. Vaccinated mice were totally protected against death, genital disease and infection of dorsal root ganglia caused by both viruses, but somewhat better protected against vaginal titers after HSV-2 infection. Overall, in the two experiments, the mRNA vaccine prevented death and genital disease in 54/54 (100%) mice infected with HSV-1 and 20/20 (100%) with HSV-2, and prevented HSV DNA from reaching the dorsal root ganglia, the site of virus latency, in 29/30 (97%) mice infected with HSV-1 and 10/10 (100%) with HSV-2. We consider the HSV-2 trivalent mRNA vaccine to be a promising candidate for clinical trials for prevention of both HSV-1 and HSV-2 genital herpes.

Chimeric spike mRNA vaccines protect against Sarbecoviruschallenge in mice

“…As previous studies demonstrated the successful delivery of more than one HSV-2 glycoprotein to broaden antigen coverage via mRNA vaccination (31)(32)(33), we sought to determine if simultaneous immunization with mRNA-LNP expressing the chimeric spikes of diverse sarbecoviruses was a feasible strategy to elicit broadly binding and neutralizing antibodies. As aged human populations are the most susceptible to severe COVID-19 disease and death, we sought to examine the protective efficacy of our vaccines in aged mouse models that develop severe disease and death following sarbecovirus infection.…”

Herpes Simplex Virus Cell Entry Mechanisms: An Update

“…The most common glycoprotein in these vaccines is gD. Other glycoproteins such as gB, gC, gE, gK were utilized in vaccines as well ( Corey et al., 1999 ; Stanfield et al., 2014 ; Awasthi et al., 2017 ; Egan et al., 2020 ). Unfortunately, some vaccines efficient in animal models failed in human clinical trials and were ceased recently.…”

“…Fortunately, some vaccines are continuing their clinical trials. The following vaccines are currently in clinical trials or show excellent results in preclinical trials: COR-1 ( Dutton et al., 2016 ; Chandra et al., 2019 ), NE-HSV2 ( Truong et al., 2019 ), HSV-2 trivalent vaccine ( Awasthi et al., 2014 ; Awasthi et al., 2017 ; Egan et al., 2020 ), G103 ( Odegard et al., 2016 ), HSV529 ( Bernard et al., 2015 ; Dropulic et al., 2017 ; Dropulic et al., 2019 ), RVX201 ( Halford et al., 2011 ), VC2, R2 ( Richards et al., 2017 ; Bernstein et al., 2020 ), HSV2 ΔgD2 ( Dropulic et al., 2017 ; Burn et al., 2018 ), and HSV-2 trivalent mRNA ( Egan et al., 2020 ). Hopefully, one or more of these may be developed into a successful vaccine to control HSV infection in the human population.…”

A Protein Assembly Hypothesis for Population-Specific Decrease in Dementia with Time

“…Data suggest that vaccines for HSV-6A and HSV-7 should also be high on the priority list [7]. Vaccines are already in development for HSV-1 and HSV-2 infections (review [35]).…”