An oral NoV-rAd5 vaccine with built-in dsRNA adjuvant elicits systemic immune responses in mice

Int Immunopharmacol. 2023 Mar:116:109801. doi: 10.1016/j.intimp.2023.109801. Epub 2023 Feb 11.

Abstract

Norovirus (NoV) is an enteric pathogen notorious for causing epidemics of acute gastroenteritis. An effective vaccine against NoV is therefore urgently needed. A short double-stranded RNA (dsRNA) has been described that acts as a retinoic-acid-inducible gene-I agonist to induce the production of type I interferon; it also exhibits adjuvant activity. Using built-in dsRNA of different lengths (DS1 and DS2), we developed a recombinant adenovirus 5 (rAd5) expressing NoV VP1, and evaluated its immunogenicity following oral administration in a mouse model. An in vitro study demonstrated that the dsRNA adjuvants significantly enhanced VP1 protein expression in infected cells. The oral administration of both rAd5-VP1-DS vaccines elicited high serum levels of VP1-specific IgG and blocking antibodies, as well as strong and long-lasting mucosal immunity. There was no apparent difference in immunostimulatory effects in immunised mice between the two dsRNA adjuvants. This study indicates that an oral NoV-rAd5 vaccine with a built-in dsRNA adjuvant may be developed to prevent NoV infection in humans.

Keywords: DsRNA; Human noroviruses; RIG-I; Recombinant adenoviruses; Vaccine.

MeSH terms

  • Adenoviridae / genetics
  • Adenovirus Vaccines*
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Viral
  • Humans
  • Immunity, Mucosal
  • Mice
  • Mice, Inbred BALB C
  • Norovirus* / genetics
  • RNA, Double-Stranded
  • Vaccines, Synthetic
  • Viral Vaccines*

Substances

  • Viral Vaccines
  • Adenovirus Vaccines
  • RNA, Double-Stranded
  • Antibodies, Viral
  • Vaccines, Synthetic
  • Adjuvants, Immunologic