Nasal vaccines for pertussis

Schmitt, Pauline; Borkner, Lisa; Jazayeri, Seyed Davoud; McCarthy, K.; Mills, Kingston H.G.

doi:10.1016/j.coi.2023.102355

Cited by 5 publications

(1 citation statement)

References 44 publications

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“…However, challenges persist in vaccination strategies that require resolution. One such challenge is that current vaccines, particularly acellular vaccines, are incapable of reducing the risk of bacterial colonization in the upper respiratory tract (24,25). Consequently, disease transmission may still occur even in vaccinated individuals.…”

Section: Introductionmentioning

confidence: 99%

Use of Mucosally Administered Outer Membrane Vesicles Derived fromBordetella pertussisto Diminish Nasal Bacterial Colonization

Rudi,

Gaillard,

Bottero

et al. 2024

Preprint

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Background: We previously identified Bordetella pertussis-derived outer membrane vesicles (OMVs) as a promising immunogen for improving pertussis vaccines. In this study, we evaluated the efficacy of our vaccine prototype in immunization strategies aimed at reducing disease transmission by targeting colonization in the upper airways while maintaining protection against severe disease by reducing colonization in the lower respiratory tract. Methods: We assessed different mucosal administration strategies in a murine model, including homologous 2-dose schedules and heterologous prime-boost strategies combining intramuscular (IM) systemic immunization with mucosal routes (intranasal (IN) or sublingual (SL)). We utilized mucosal c-di-AMP and/or systemic alum adjuvants to formulate the OMV vaccine prototype. A homologous IM immunization schedule and commercial vaccines were used for comparison. Results: All tested heterologous schemes induced higher levels of specific IgG with significant avidity, as well as high levels of IgG1 and IgG2 compared, to corresponding homologous 2-dose schemes via mucosal routes (OMVIN-IN or OMVSL-SL). High IgA levels were observed post-B. pertussis challenge following OMVIN-IN treatments and heterologous treatments where the second dose was administered via a mucosal route. Furthermore, schemes involving the intranasal route, whether in a homologous or heterologous scheme, induced the highest levels of IL-17 and IFN-γ. Accordingly, these schemes showed superior efficacy against nasal colonization than the commercial vaccines. Specifically, homologous intranasal immunization exhibited the highest protective capacity against nasal colonization while maintaining an excellent level of protection in the lower respiratory tract. To enhance the protective capacity against nasal colonization further, we conducted a comparative analysis of formulations containing different adjuvants (c-di-AMP, alum, or a combination of both) administered via homologous intranasal routes. These assays revealed that the use of alum, either alone or in combination with c-di-AMP, did not enhance the immune protective capacity. Conclusions: All the experiments presented here highlight that the use of OMVs, regardless of the scheme utilized, with the exception of OMVSL-SL, outperformed acellular pertussis (aP) vaccines, achieving a greater reduction in bacterial colonization in the upper respiratory tract (p<0.001).

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Section: Introductionmentioning

confidence: 99%

Use of Mucosally Administered Outer Membrane Vesicles Derived fromBordetella pertussisto Diminish Nasal Bacterial Colonization

Rudi,

Gaillard,

Bottero

et al. 2024

Preprint

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Editorial overview: The march of mucosal vaccines

Lavelle,

Genescà

2024

Current Opinion in Immunology

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Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice

Mitchell,

Scanlon,

Flowers

et al. 2024

Journal of Leukocyte Biology

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Many respiratory infections are selectively injurious to infants, yet the etiology of age-associated susceptibility is unknown. One such bacterial pathogen is Bordetella pertussis. In adult mice, innate interferon-gamma (IFN-γ) is produced by natural killer (NK) cells and restricts infection to the respiratory tract. In contrast, infant pertussis resembles disease in NK cell- and IFN-γ -deficient adult mice that suffer disseminated lethal infection. We hypothesized that infants exhibit age-associated deficits in NK cell frequency, maturation, and responsiveness to B. pertussis, associated with low IFN-γ levels. To delineate mechanisms behind age-dependent susceptibility, we compared infant and adult mouse models of infection. Infection in infant mice resulted in impaired upregulation of IFN-γ and substantial bacterial dissemination. B. pertussis-infected infant mice displayed fewer pulmonary NK cells than adult mice. Furthermore, the NK cells in the infant mouse lungs had an immature phenotype, and the infant lung showed no upregulation of the IFN-γ-inducing cytokine IL-12p70. Adoptive transfer of adult NK cells into infants, or treatment with exogenous IFN-γ, significantly reduced bacterial dissemination. These data indicate that the lack of NK cell-produced IFN-γ significantly contributes to infant fulminant pertussis and could be the basis for other pathogen-induced, age-dependent respiratory diseases.

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Nasal vaccines for pertussis

Cited by 5 publications

References 44 publications

Use of Mucosally Administered Outer Membrane Vesicles Derived fromBordetella pertussisto Diminish Nasal Bacterial Colonization

Use of Mucosally Administered Outer Membrane Vesicles Derived fromBordetella pertussisto Diminish Nasal Bacterial Colonization

Editorial overview: The march of mucosal vaccines

Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice

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