Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine

Abstract

The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice. The comparison revealed essential qualitative and quantitative differences with respect to immunogenicity and adverse effects for these vaccines. Both vaccines stimulated a mixed systemic Th1/Th2/Th17 response. Remarkably, omvPV evoked higher IgG levels, lower systemic pro-inflammatory cytokine responses and enhanced splenic gene expression than wPV. The omvPV-induced transcriptome revealed gene signatures of the IFN-signaling pathway, anti-inflammatory signatures that attenuate LPS responses, anti-inflammatory metabolic signatures, and IgG responses. Upon intranasal challenge, both immunized groups were equally efficient in clearing Bordetella pertussis from the lungs. This study importantly shows that immunization with omvPV provides a milder inflammatory responses but with equal protection to bacterial colonization and induction of protective antibody and Th1/Th17 type immune responses compared to wPV. These results emphasize the potential of omvPV as a safe and effective next-generation pertussis vaccine.

Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination

“…8 Subcutaneous immunization of outer membrane vesicle pertussis vaccine (omvPV) could be an improved alternative, as it elicits high serum IgG levels against a broad antigen range 10 and a mixed Th1, Th17, and Th2 response. 11 This response is comparable to the response induced by a B. pertussis infection, but importantly lacks the mucosal immune responses. 8,[12][13][14] Vaccine administration directly into the respiratory tract provides better protection, compared with intramuscular administration, because of its induction of local immune responses.…”

In silicoidentification and modification of T cell epitopes in pertussis antigens associated with tolerance

“…First, lessons were learnt from broadly studied differences between the efficacy of wPV and aPV and between vaccines and natural infections. In this regard, omvPV were found to induce broad antibody responses and a mixed Th1/Th17-dominated T cell response in mice, resembling responses induced by wPV 21 and infection. 45 However, though responses to infection often serve as a reference, we know from past studies that natural infections confer improved protection compared to current vaccines, but do not promote life-long immunity to Bp.…”

“…Previous studies with omvPVs have shown that they confer protection in mice after both subcutaneous and mucosal immunization with a mixed Th1/Th17 response, similar to the response induced by infection. [19][20][21] These results suggest that omvPVs have the potential to be a safe and effective next-generation pertussis vaccine.…”

Immunomodulation as a Novel Strategy for Prevention and Treatment of Bordetella spp. Infections

“…and characterizing the immune response as well as protective immunity (285)(286)(287)(288)(289)(290)(291)(292)(293)(294)(295). In animal studies, immunization with outer membrane vesicles led to not only better humoral and cellular (Th17) memory, but also to a significant increase in IgA titers, which is one of the major hurdles of current vaccination strategies against this pathogen (296)(297)(298). It is important to highlight that the increase in IgA responses upon immunization with outer membrane vesicles is only obtained when these are administrated mucosally (299).…”