Filling two needs with one deed: a combinatory mucosal vaccine against influenza A virus and respiratory syncytial virus

Front Immunol. 2024 Jun 21:15:1376395. doi: 10.3389/fimmu.2024.1376395. eCollection 2024.

Abstract

Influenza A Virus (IAV) and Respiratory Syncytial Virus (RSV) are both responsible for millions of severe respiratory tract infections every year worldwide. Effective vaccines able to prevent transmission and severe disease, are important measures to reduce the burden for the global health system. Despite the strong systemic immune responses induced upon current parental immunizations, this vaccination strategy fails to promote a robust mucosal immune response. Here, we investigated the immunogenicity and efficacy of a mucosal adenoviral vector vaccine to tackle both pathogens simultaneously at their entry site. For this purpose, BALB/c mice were immunized intranasally with adenoviral vectors (Ad) encoding the influenza-derived proteins, hemagglutinin (HA) and nucleoprotein (NP), in combination with an Ad encoding for the RSV fusion (F) protein. The mucosal combinatory vaccine induced neutralizing antibodies as well as local IgA responses against both viruses. Moreover, the vaccine elicited pulmonary CD8+ and CD4+ tissue resident memory T cells (TRM) against the immunodominant epitopes of RSV-F and IAV-NP. Furthermore, the addition of Ad-TGFβ or Ad-CCL17 as mucosal adjuvant enhanced the formation of functional CD8+ TRM responses against the conserved IAV-NP. Consequently, the combinatory vaccine not only provided protection against subsequent infections with RSV, but also against heterosubtypic challenges with pH1N1 or H3N2 strains. In conclusion, we present here a potent combinatory vaccine for mucosal applications, which provides protection against two of the most relevant respiratory viruses.

Keywords: adjuvant; combinatory vaccine; influenza A virus (IAV); mucosal immunity; respiratory syncytial virus (RSV); respiratory viruses.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / immunology
  • Female
  • Genetic Vectors
  • Humans
  • Immunity, Mucosal*
  • Influenza A virus* / immunology
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / immunology
  • Mice
  • Mice, Inbred BALB C*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Respiratory Syncytial Virus Infections* / immunology
  • Respiratory Syncytial Virus Infections* / prevention & control
  • Respiratory Syncytial Virus Vaccines* / administration & dosage
  • Respiratory Syncytial Virus Vaccines* / immunology
  • Respiratory Syncytial Viruses / immunology
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / immunology

Substances

  • Influenza Vaccines
  • Respiratory Syncytial Virus Vaccines
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Vaccines, Combined

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Deutsche Forschungsgemeinschaft (DFG) through the research training group RTG 2504 (project 761 number: 401821119, to AA, MT). Further support was received from the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg (Advanced Project A90; Junior Project 100).