Abstract
IntroductionVaricella‐zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. A live attenuated vaccine (LAV) and glycoprotein E (gE) subunit vaccine were developed to prevent VZV‐induced diseases. We recently reported that single‐strand RNA (ssRNA) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (CrPV) is an effective adjuvant for protein‐based and virus‐like particle‐based vaccines. Here, Chinese hamster ovary expression system and an LAV from Oka/SK strains.MethodsWe appraised the adjuvant effect of the same CrPV ssRNA encoding the gE gene formulated in the two vaccines using VZV‐primed C57BL/6 mice and guinea pigs. Humoral immunity and cell‐mediated immunity were assessed by enzyme‐linked immunosorbent assay (ELISA) and ELISPOT in gE subunit vaccine and by ELISA and fluorescent antibody to membrane antigen in LAV.ResultsThe gE subunit vaccine‐induced gE‐specific antibodies and CD4+ T‐cell responses (indicated by interferon‐γ [IFN‐γ] and interleukin‐2 secretion) in the ssRNA‐based adjuvant containing the VZV gE gene. Therefore, an ssRNA adjuvant combined with gE antigen can trigger the innate immune response and induce an adaptive immune response to ultimately activate humoral and cell‐mediated responses. VZV LAV could also induce VZV‐specific antibodies and IFN‐γ stimulated by LAV, whereas the effect of ssRNA as a vaccine adjuvant could not be confirmed. However, the ssRNA adjuvant increased VZV‐specific neutralizing antibody response.ConclusionsTaken together, these results highlight that the gE subunit vaccine and LAV developed in this study can be functional VZV vaccines, and ssRNAs appear to function better as adjuvants in a subunit vaccine than in an LAV.
Highlights
Varicella‐zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia
We showed the potential of single‐strand RNA (ssRNA) adjuvants to compensate for the limitations of protein‐based vaccines with respect to low T‐cell activity and short‐term responses, as well as to increase the neutralizing antibody in live attenuated vaccine (LAV) for preventing VZV‐induced disease
SsRNA is recognized by TLR7 and/or TLR8, which are highly expressed in antigen‐presenting cells (APCs) to stimulate an adaptive immune response for antigen‐specific T
Summary
Varicella‐zoster virus (VZV) induces chickenpox (varicella), shingles (herpes zoster), and/or postherpetic neuralgia. Alum typically induces a Th2 response, which mediates the differentiation of B cells that secrete Th2‐cell‐ associated antibody isotypes, as opposed to inducing a very low Th1 response that is required to activate innate immune response,[20,21] as a prerequisite to guarantee a more effective and/or long‐term immune response.[22] The ideal adjuvant induces innate immune responses, thereby activating adaptive immune responses.[23,24] Toll‐like receptor (TLR) agonists and oil‐in‐water emulsions have been developed to complement alum adjuvants.[25,26] Our new candidate adjuvant is a single‐strand RNA (ssRNA) derived from the cricket paralysis virus (CrPV) intergenic region (IGR) of the internal ribosome entry site (IRES) It induces balanced Th1/Th2 responses, enhances innate immune response, and increases vaccine efficacy.[27]. Platform consisted of four restriction enzyme sequences and a multicloning site between the untranslated regions to permit the insertion of the VZV ORF68 (gE) gene
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