Importance of (antibody-dependent) complement-mediated serum killing in protection against<i>Bordetella pertussis</i>

Geurtsen, Jeroen; Faé, Kellen C.; Dobbelsteen, Germie P. J. M. van den

doi:10.1586/14760584.2014.944901

Cited by 12 publications

(9 citation statements)

References 125 publications

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“…With respect to the antibody responses to these antigens, these were found to resemble antibody responses to natural B. pertussis infection in humans 29,30 and mice 16 . These broad antibody responses induced by omvPV may provide protection through multiple antibody mechanisms such as opsonizing and bactericidal activity as well as prevention of bacterial adhesion 31,32 . However, the functionality of omvPV-induced IgG and IgA antibodies remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

Raeven

Rockx-Brouwer

Kanojia

et al. 2020

Sci Rep

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A vaccine based on outer membrane vesicles of pertussis (omvpV) is protective in a mouse-challenge model and induces a broad antibody and mixed Th1/Th2/Th17 response against multiple antigens following subcutaneous immunization. However, this route did not result in mucosal immunity and did not prevent nasopharyngeal colonization. in this study, we explored the potential of intranasal immunization with omvpV. only intranasal immunization induced strong mucosal immune responses that encompasses enhanced pulmonary and nasal IgA antibody levels, mainly directed against Vag8 and LpS. furthermore, high numbers of igA-and igG-producing plasma cells were detected as well as lung-resident IgA memory B-cells. Finally, only intranasal immunization induced pulmonary Th1/ Th17-related cytokine responses. The magnitude and type of systemic immunity was comparable between both routes and included high systemic igG antibody levels, strong igG-producing plasma cell responses, memory B-cells residing in the spleen and systemic Th1/Th2/Th17-related cytokine responses. importantly, only intranasal immunization prevented colonization in both the lungs and the nasal cavity. In conclusion, intranasal omvPV immunization induces mucosal IgA and Th17-mediated responses without influencing the systemic immunity profile. These responses resulted in prevention of Bordetella pertussis colonization in the respiratory tract, including the nasal cavity, thereby potentially preventing transmission.

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Section: Discussionmentioning

confidence: 99%

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

Raeven

Rockx-Brouwer

Kanojia

et al. 2020

Sci Rep

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“…Emerging data point to a potentially critical role of complement in protection following various clinically approved vaccines (Frasch et al, 2009; Geurtsen et al, 2014) as well as experimental vaccines (McCoy et al, 2013), pointing to a role for vaccine-induced antibody-driven complement deposition as a potentially key predictor of immunity. While various assays have been developed to measure complement activity in human plasma, a sample-sparing, high-throughput assay could provide critical value for the evaluation and dissection of complement-activating antibodies.…”

Section: Introductionmentioning

confidence: 99%

A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation

Fischinger

Fallon

Michell

et al. 2019

Journal of Immunological Methods

171

131

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The complement system plays a critical role in innate immune defense against pathogens, both via non-specific direct pathogen recognition and killing or via antigen-specific indirect recruitment by complement fixing antibodies. While various assays for measuring complement activation have been developed, few provide a high-throughput, sample-sparing approach to interrogate the qualitative differences in the ability of antibodies to drive complement activation. Here we present a high-throughput, sample-sparing, bead-based assay to evaluate antigen-specific antibody-dependent complement activation against nearly any antigen. Optimization of buffer composition, kinetics of immune complex formation, as well as complement source all contribute critically to the development of a robust, highly flexible and high-throughput approach to analyze antibody-dependent complement deposition (ADCD). Thus, the optimized bead-based, antigen-specific assay represents a simple, highly adaptable platform to profile antibody-dependent complement activation across pathogens and diseases.

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“…Several studies have reported that B. pertussis has developed strategies for immune evasion, including the ability to bind complement-regulatory proteins (Barnes and Weiss, 2001;Berggård et al, 2001;Amdahl et al, 2011;Marr et al, 2011;Geurtsen et al, 2014;Hovingh et al, 2017). The two Bvgactivated autotransporter proteins Vag8 and BrkA are known to be involved in complement resistance by binding C1 esterase inhibitor (C1-INH) (Marr et al, 2011) or preventing the deposition of C3 onto the bacteria and the formation of the membrane attack complex (Barnes and Weiss, 2001).…”

Section: Introductionmentioning

confidence: 99%

Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains

et al. 2020

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Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn.

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Importance of (antibody-dependent) complement-mediated serum killing in protection againstBordetella pertussis

Cited by 12 publications

References 125 publications

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation

Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains

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