Immunogenicity of Live Attenuated B. pertussis BPZE1 Producing the Universal Influenza Vaccine Candidate M2e

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.

Attenuated Bordetella pertussis Vaccine Protects against Respiratory Syncytial Virus Disease via an IL-17–Dependent Mechanism

“…After priming with BPZE1 in the neonatal period, this beneficial effect lasts through to adulthood and the effects are dependent on the induction of IL-17. Because BPZE1 can be genetically manipulated to express additional antigens (49,50), it may in the future be used as a live attenuated vaccine vector to deliver antigens from additional pathogens (including RSV), thus providing polyvalent protection against multiple respiratory infections by both specific and nonspecific immunologic effects. n Author disclosures are available with the text of this article at www.atsjournals.org.…”

Presenting Influenza A M2e Antigen on Recombinant Spores of Bacillus subtilis

“…In contrast, use of B . pertussis as a live M2e antigen carrier failed to induce antibody production in intranasally immunized mice [38]. …”

Coqueluche : une perspective globale

“…Il est essentiel de mettre au point de nouveaux vaccins qui sont plus efficaces avec une durée de protection plus longue. Les nouvelles technologies, telles que les vaccins anticoquelucheux vivants atténués 20 et les vaccins avec de nouveaux adjuvants qui dirigent le système immunitaire vers une réponse du type Th1…”