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

Shahin, Roberta D.; Hamel, Josée; Leef, Mary F.; Brodeur, Bernard R.

doi:10.1128/iai.62.2.722-725.1994

Cited by 26 publications

(16 citation statements)

References 18 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

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“…The expression of band A LPS has been suggested as being important for full virulence. Monoclonal antibodies (mAbs) specific for band A LPS are able to inhibit the invasion of HeLa cells by 6. pertussis (Ewanowich etal., 1989) and to adoptively transfer immunity to infection in an infant mouse lung infection model (Shahin et a/., 1994).…”

Section: Introductionmentioning

confidence: 99%

The identification, cloning and mutagenesis of a genetic locus required for lipopolysaccharide biosynthesis in Bordetella pertussis

Allen

Maskell

1996

Molecular Microbiology

114

135

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Bordetella pertussis lipopolysaccharide (LPS) is biologically active, being both toxic and immunogenic. Using transposon mutagenesis we have identified a genetic locus required for the biosynthesis of LPS in B. pertussis, which has been cloned and sequenced. We have also identified equivalent loci in Bordetella bronchiseptica and Bordetella parapertussis and cloned part of it from B. parapertussis. The amino acid sequences derived from most of the genes present in the sequenced B. pertussis locus are similar to proteins required for the biosynthesis of LPS and other complex polysaccharides from a variety of bacteria. The genes are in a unique arrangement in the locus. Several of the genes identified are similar to genes previously shown to play specific roles in LPS O-antigen biosynthesis. In particular, the amino acid sequence derived from one of the genes is similar to the enzyme encoded by rfbP from Salmonella enterica, which catalyses the transfer of galactose to the undecaprenol phosphate antigen carrier lipid as the first step in building oligosaccharide O-antigen units, which are subsequently assembled to form polymerized O-antigen structures. Defined mutation of this gene in the B. pertussis chromosome results in the inability to express band A LPS, possibly suggesting that the trisaccharide comprising band A is a single O-antigen-like structure and that B. pertussis LPS is similar to semi-rough LPS seen in some mutants of enteric bacteria.

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

Cited by 26 publications

References 18 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

The identification, cloning and mutagenesis of a genetic locus required for lipopolysaccharide biosynthesis in Bordetella pertussis

Erythroid Suppressor Cells Compromise Neonatal Immune Response against Bordetella pertussis

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