The role of vaccination route with an adenovirus-vectored vaccine in protection, viral control, and transmission in the SARS-CoV-2/K18-hACE2 mouse infection model

Front Immunol. 2023 Aug 16:14:1188392. doi: 10.3389/fimmu.2023.1188392. eCollection 2023.

Abstract

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival.

Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed that animals vaccinated intranasally had improved cellular and mucosal antibody responses. Additionally, intranasally vaccinated animals had significantly better viremic control, and protection from lethal infection compared to intramuscularly vaccinated animals. Notably, in a novel transmission model, intranasal vaccination reduced viral transmission to naïve co-housed mice compared to intramuscular vaccination.

Discussion: Our data provide convincing evidence for the use of intranasal vaccination in protecting against SARS-CoV-2 infection and transmission.

Keywords: SARS-CoV-2; intramuscular vaccination; intranasal vaccination; vaccine efficacy; vaccine immunogenicity; virus transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae Infections*
  • Adenovirus Vaccines*
  • Animals
  • Animals, Genetically Modified
  • COVID-19* / prevention & control
  • Mice
  • SARS-CoV-2
  • Vaccination
  • Vaccines*

Substances

  • Adenovirus Vaccines
  • K-18 conjugate
  • Vaccines

Grants and funding

Funding was provided through a contract research agreement 000217, and the Saint Louis University COVID-19 research fund.