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

Hana Kammoun,Marina De Filette,Nathalie Mielcarek,Xavier Roux,Camille Locht,Dominique Raze,Anne-Sophie Debrie,Walter Fiers,Tine Ysenbaert,Xavier Saelens,Daniela Flavia Hozbor

doi:10.1371/journal.pone.0059198

Abstract

BackgroundIntranasal 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 FindingsWe 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/SignificanceUsing 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.

Highlights

Respiratory pathogens are the leading cause of global deaths from infectious diseases [1]
We show here that the BPZE1 derivative producing Fha44-M2 protein (M2e) is able to induce an immune response only in the absence of fulllength filamentous hemagglutinin (FHA)
Three copies of the M2ecoding sequence were fused to the Fha44-coding sequence

Summary

Introduction

Respiratory pathogens are the leading cause of global deaths from infectious diseases [1]. Most antigens are poorly immunogenic when applied by the nasal route, and potent adjuvants are often needed Examples of such adjuvants include genetically detoxified cholera toxin and the related Escherichia coli heat-labile enterotoxin, which are among the most potent mucosal adjuvants known. Their i.n. application in the formulation of an influenza vaccine has raised safety concerns as it resulted in unacceptable adverse events, such as Bell’s palsy [3]. Intranasal delivery of vaccines directed against respiratory pathogens is an attractive alternative to parenteral administration 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

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Results

Conclusion