Immunogenicity of live attenuated B. pertussis BPZE1 producing the universal influenza vaccine candidate M2e

PLoS One. 2013;8(3):e59198. doi: 10.1371/journal.pone.0059198. Epub 2013 Mar 19.

Abstract

Background: Intranasal delivery of vaccines directed against respiratory pathogens is an attractive alternative to parenteral administration. However, using this delivery route for inactivated vaccines usually requires the use of potent mucosal adjuvants, and no such adjuvant has yet been approved for human use.

Methodology/principal findings: We have developed a live attenuated Bordetella pertussis vaccine, called BPZE1, and show here that it can be used to present the universal influenza virus epitope M2e to the mouse respiratory tract to prime for protective immunity against viral challenge. Three copies of M2e were genetically fused to the N-terminal domain of filamentous hemagglutinin (FHA) and produced in recombinant BPZE1 derivatives in the presence or absence of endogenous full-length FHA. Only in the absence of FHA intranasal administration of the recombinant BPZE1 derivative induced antibody responses to M2e and effectively primed BALB/c mice for protection against influenza virus-induced mortality and reduced the viral load after challenge. Strong M2e-specific antibody responses and protection were observed after a single nasal administration with the recombinant BPZE1 derivative, followed by a single administration of M2e linked to a virus-like particle without adjuvant, whereas priming alone with the vaccine strain did not protect.

Conclusions/significance: Using recombinant FHA-3M2e-producing BPZE1 derivatives for priming and the universal influenza M2e peptide linked to virus-like particles for boosting may constitute a promising approach for needle-free and adjuvant-free nasal vaccination against influenza.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology*
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood*
  • Bordetella pertussis / genetics
  • Bordetella pertussis / immunology*
  • Humans
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Respiratory System / drug effects
  • Respiratory System / immunology
  • Respiratory System / virology
  • Survival Analysis
  • Vaccination
  • Vaccines, Synthetic
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*
  • Virulence Factors, Bordetella / genetics
  • Virulence Factors, Bordetella / immunology*

Substances

  • Adhesins, Bacterial
  • Antibodies, Viral
  • Influenza Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Viral Matrix Proteins
  • Virulence Factors, Bordetella
  • filamentous hemagglutinin adhesin, Bordetella pertussis

Grants and funding

This work was supported by a grant from the European Commission under the grant agreement #201502 (Child-Innovac). HK holds a fellowship of Institut Pasteur de Lille and University Lille 2. Research related to M2e-based influenza vaccines in the group of XS is supported by FWO-Vlaanderen project G.0375.10N., Ghent University IOF-grant Stepstone IOF08/STEP/001, and a research collaboration with Sanofi Pasteur. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.