Herpes simplex virus (HSV) is a prevalent virus worldwide that is capable of causing a range of diseases, including mucocutaneous lesions in oral and genital regions. More importantly, HSV can cause encephalitis or meningitis under rare circumstances. As a result of the complicated membrane fusion mechanism of HSV, there are still no licensed vaccines at present, although many HSV vaccines are in the clinical trial stage. gD, gH, gL and gB are the main HSV membrane glycoproteins involved in the fusion process. When triggered by receptor binding or exposure to acidic pH, the gB protein undergoes a conformational change, in which hydrophobic residues are inserted into the host membrane. It then folds back on itself to bring the virus and host membranes together. In this study, we designed a sequence to replace histidine 516 in gB with a proline to stabilize the prefusion gB structure. Three different formulations of the vaccine were developed: a subunit vaccine incorporating oligodeoxynucleotides with CpG motifs (CpG ODNs) and QS-21 as adjuvants, a subunit vaccine with an alum adjuvant, and an mRNA vaccine. BALB/c mice were injected intramuscularly with the vaccines to evaluate the immunogenicity of gB and gB H516P and to assess the efficacy of QS-21 and CpG ODNs as adjuvants. The results revealed that the immunogenicity of the gB and gB H516P proteins did not significantly affect humoral and cellular immune responses. However, the combination of QS-21 and CpG ODNs enhanced cellular immune responses compared with the alum adjuvant, but there was no significant difference in neutralizing antibody titers. After being infected with the HSV-1 Mckrae wild-type strain, all the vaccine groups of BALB/c mice were protected from infection, and the mice did not die or experience obvious loss of body weight.
Keywords: HSV-1; Prefusion mutation; Subunit vaccine; gB; mRNA vaccine.
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