A bactericidal monoclonal antibody specific for the lipooligosaccharide of Bordetella pertussis reduces colonization of the respiratory tract of mice after aerosol infection with B. pertussis

Mountzouros, K T; Kimura, Alan; Cowell, J L

doi:10.1128/iai.60.12.5316-5318.1992

Cited by 35 publications

(11 citation statements)

References 12 publications

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“…Obviously, such results are in contrast to numerous studies demonstrating that passive transfer of pertussis-specific antibodies, especially when produced by immunization with purified pertussis antigen or acellular vaccines, are able to protect against pertussis infection (10)(11)(12)(13)(14). We cannot exclude the possibility that undetectable pertussis-specific antibodies, produced locally after transfer of primed B cells and/or accelerated with help from primed CD4 ϩ T cells upon challenge, are responsible for the observed reconstitution of protection ( Fig.…”

Section: Discussioncontrasting

confidence: 78%

Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production

Leef

Elkins

Barbić

et al. 2000

The Journal of Experimental Medicine

113

103

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To investigate the fundamental nature of protective immunity to Bordetella pertussis, we studied intranasal immunization of adult mice with formalin-fixed B. pertussis (FFBP), followed by aerosol B. pertussis challenge. Mice given two doses of FFBP intranasally completely cleared a subsequent pertussis aerosol challenge from tracheae and lungs (defined as protection), but there was no correlation between levels of specific antibody and clearance of bacteria. Further, transfer of immune serum before aerosol challenge had minimal effects on bacterial burdens. However, pertussis-specific T cells producing interferon γ but not interleukin 4 or interleukin 10 were detected in draining lymph nodes of FFBP-immunized mice. Significantly, repeated immunization of B cell knockout (BKO) mice resulted in partial protection, and complete protection was reconstituted by transfer of pertussis-immune B cells; reconstituted BKO mice had little if any detectable antipertussis antibodies. Immunization of mice lacking all T cells or lacking CD4+ T cells did not lead to protection; in contrast, CD8− mice were protected. Mice depleted of CD4+ T cells after immunization but before aerosol challenge, which thus had normal amounts of specific antibodies, were not optimally protected. Taken together, these data indicate that protective immunity to pertussis is dependent on both CD4+ T cells and B cells, and both cell types provide significant functions other than specific antibody production.

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Section: Discussioncontrasting

confidence: 78%

Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production

Leef

Elkins

Barbić

et al. 2000

The Journal of Experimental Medicine

113

103

View full text Add to dashboard Cite

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“…Although specific correlates of protection have not been fully defined, the use of vaccines over decades has proven to be highly effective in reducing the disease worldwide. Acellular pertussis vaccines and whole-cell pertussis vaccines (Pw) are available, and various studies have demonstrated the importance of vaccine-induced Abs against B. pertussis virulence factors, including pertussis toxin, fimbria (fim 2 and fim 3) and pertactin (11)(12)(13)(14)(15). However, it has been difficult to establish a direct correlation between Ab titers and protection from disease (16,17).…”

mentioning

confidence: 99%

Erythroid Suppressor Cells Compromise Neonatal Immune Response against Bordetella pertussis

Dunsmore

Bozorgmehr

Delyea

et al. 2017

The Journal of Immunology

106

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Newborns are highly susceptible to infection. The underlying mechanism of neonatal infection susceptibility has generally been associated with neonatal immune cell immaturity. In this study, we challenged this notion and built upon our recent discovery that neonates are physiologically enriched with erythroid TER119CD71 cells (Elahi et al. 2013. 504: 158-162). We have used, a common neonatal respiratory tract infection, as a proof of concept to investigate the role of these cells in newborns. We found that CD71 cells have distinctive immune-suppressive properties and suppress innate immune responses against infection. CD71 cell ablation unleashed innate immune response and restored resistance to infection. In contrast, adoptive transfer of neonatal CD71 cells into adult recipients impaired their innate immune response to infection. Enhanced innate immune response to was characterized by increased production of protective cytokines IFN-γ, TNF-α, and IL-12, as well as recruitment of NK cells, CD11b, and CD11c cells in the lung. Neonatal and human cord blood CD71 cells express arginase II, and this enzymatic activity inhibits phagocytosis of in vitro. Thus, our study challenges the notion that neonatal infection susceptibility is due to immune cell-intrinsic defects and instead highlights active immune suppression mediated by abundant CD71 cells in the newborn. Our findings provide additional support for the novel theme in neonatal immunology that immunosuppression is essential to dampen robust immune responses in the neonate. We anticipate that our results will spark renewed investigation in modulating the function of these cells and developing novel strategies for enhancing host defense to infections in newborns.

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“…These two species differ in molecular weight as three N-acetyl amino sugars found on LOS A are not present on LOS B (5). Murine and human monoclonal antibodies to the carbohydrate portion of LOS A have been shown to be highly specific for B. pertussis, and to be bactericidal in vitro (1,2,12,13). Mountzouros et al have found that one particular monoclonal antibody specific for LOS A that is bactericidal in vitro is effective in reducing colonization in a mouse model of B. pertussis respiratory infection (13).…”

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confidence: 99%

Analysis of protective and nonprotective monoclonal antibodies specific for Bordetella pertussis lipooligosaccharide

et al. 1994

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In this study, it has been determined that immunoglobulin Gl (IgGl) and IgG3 monoclonal antibodies directed to the lipooligosaccharide A of Bordetella pertussis were able to protect mice from fatal aerosol infection. No correlation was found between the bactericidal activity in vitro in the presence of complement and the protection in mice, since a bactericidal IgG3 did not elicit protection. In addition, no significant difference in protective capacity was observed with bactericidal and nonbactericidal IgGl antibodies, indicating that bactericidal activity is not a requirement for protection mediated by certain anti-lipooligosaccharide A antibodies. A reduction in protection in C5-deficient mice was observed, suggesting a significant role for complement in certain host defense mechanisms against B. pertussis infection.

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A bactericidal monoclonal antibody specific for the lipooligosaccharide of Bordetella pertussis reduces colonization of the respiratory tract of mice after aerosol infection with B. pertussis

Cited by 35 publications

References 12 publications

Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production

Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production

Erythroid Suppressor Cells Compromise Neonatal Immune Response against Bordetella pertussis

Analysis of protective and nonprotective monoclonal antibodies specific for Bordetella pertussis lipooligosaccharide

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