Influenza vaccine efficacy induced by orally administered recombinant baculoviruses

PLoS One. 2020 May 27;15(5):e0233520. doi: 10.1371/journal.pone.0233520. eCollection 2020.

Abstract

Although vaccine delivery through the oral route remains the most convenient and safest way for mass immunization purposes, this method is limited by the requirement for large antigen doses and low vaccine efficacy. In this study, we generated recombinant baculoviruses (rBVs) expressing influenza hemagglutinin (A/PR/8/34) and orally delivered a low dose of rBVs to evaluate its vaccine efficacy in mice. Intranasal rBV vaccination was included in the whole experiment for comparison. We found that oral vaccination elicited high levels of virus-specific IgG and IgA antibody responses in both serum and mucosal samples (lung, tracheal, intestinal, fecal and vaginal). Surprisingly, complete protection from the lethal influenza challenge was observed, as indicated by reductions in the virus titer, inflammatory cytokine production, body weight change, and enhanced survival. These results suggest that oral delivery of the influenza rBV vaccine induces mucosal and systemic immunity, which protect mice from the lethal influenza virus challenge. Oral delivery of baculovirus vaccines can be developed as an effective vaccination route.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies, Viral / immunology
  • Baculoviridae* / genetics
  • Baculoviridae* / immunology
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus* / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus* / immunology
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines* / genetics
  • Influenza Vaccines* / immunology
  • Influenza Vaccines* / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections* / genetics
  • Orthomyxoviridae Infections* / immunology
  • Orthomyxoviridae Infections* / prevention & control
  • Sf9 Cells
  • Spodoptera

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin A
  • Immunoglobulin G
  • Influenza Vaccines
  • hemagglutinin, avian influenza A virus

Grants and funding

This work was supported by grants from the National Research Foundation of Korea (NRF) (2018R1A2B6003535, 2018R1A6A1A03025124) and a grant from Cooperative Research Program for Agriculture Science & Technology Development, Rural Development Administration, Republic of Korea (Project No. PJ01320501) for providing financial support.