Protective activity of the Bordetella pertussis BrkA autotransporter in the murine lung colonization model

ABSTRACTCurrent pneumococcal vaccines are composed of capsular polysaccharides (PS) of various serotypes, either as free PS or as protein-PS conjugates. The use of pneumococcus protein antigens that are able to afford protection across the majority of serotypes is envisaged as a relevant alternative and/or complement to the polysaccharides. In this context, based on several studies, the Pht protein family emerged as relevant vaccine candidates. The purpose of the present study was to evaluate the Pht protein family in several preclinical mouse models. Immunization with these antigens was compared with immunization with other pneumococcal antigens, such as CbpA, PspA, and PsaA. In a nasopharyngeal colonization model and in a lung colonization model, the Phts were found to be superior to the other candidates in terms of efficacy of protection and serotype coverage. Likewise, vaccination with PhtD allowed higher animal survival rates after lethal intranasal challenge. Finally, a passive transfer model in which natural anti-PhtD human antibodies were transferred into mice demonstrated significant protection against lethal intranasal challenge. This indicates that natural anti-PhtD human antibodies are able to protect against pneumococcal infection. Our findings, together with the serotype-independent occurrence of the Phts, designate this protein family as valid candidate antigens to be incorporated in protein-based pneumococcal vaccines.

Download Full-text

Acellular Pertussis Vaccine from Antigens of Freshly Isolated and Vaccine Strains of Bordetella pertussis with Different Genotypic Characteristics

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2021-20-4-68-72 ◽

2021 ◽

Vol 20 (4) ◽

pp. 68-72

Author(s):

E. M. Zaitsev ◽

I. G. Bazhanova ◽

M. V. Britsina ◽

N. U. Mertsalova ◽

M. N. Ozeretskovskaya

Keyword(s):

Pertussis Vaccine ◽

Bordetella Pertussis ◽

The Body ◽

Acellular Pertussis Vaccine ◽

Protective Activity ◽

Igg Antibody ◽

Protective Antigens ◽

Promoter Gene ◽

Preclinical And Clinical Studies ◽

Genotypic Characteristics

Relevance. The development of effective and safe vaccines for pertussis prevention remains an urgent public health challenge.Aim. To study the protective activity and safety of acellular pertussis vaccine (AcPV) containing a complex of protective antigens from freshly isolated and vaccine strains of Bordetella pertussis.Materials and methods. Freshly isolated (No. 287, and No. 317) and vaccine (No. 305 and No. 475) B. pertussis strains with «non-vaccine» and «vaccine» allelic variants of the pertussis toxin (PT) subunit A gene, the PT promoter gene, the pertactin gene, the fimbria 2 gene, and the fimbria 3 gene strains were used for the production of AcPV.Results. All the studied variants of AcPV were harmless in the test of changes in the body weight of mice and sensitivity to histamine. The protective activity of AcPV3 (strains No. 287, No. 317 and No. 305) and AcPV1 (strains No. 287, No. 305 and No. 475) was higher than that of AcPV2 (strains No. 317, No. 305, and No. 475). IgG antibody titers to PT were also higher in mice immunized with AcPV1 and AcPV3.Conclusion. The higher protective activity of AcPV3 and AcPV1 may be associated with the genotype of strain No. 287, which has a ptxP3 PT promoter and is characterized by an increased level of PT production and high virulence. The most promising for further preclinical and clinical studies is AcPV3, which contains 2/3 of the antigens of the dominant «non-vaccine» genotype and 1/3 of the «vaccine» genotype, corresponding to the genes of PT, pertactin and fimbria to the currently circulating B. pertussis strains.

Download Full-text

Suppression of mucosal Th17 memory responses by acellular pertussis vaccines enhances nasal Bordetella pertussis carriage

npj Vaccines ◽

10.1038/s41541-020-00270-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Violaine Dubois ◽

Jonathan Chatagnon ◽

Anaïs Thiriard ◽

Hélène Bauderlique-Le Roy ◽

Anne-Sophie Debrie ◽

...

Keyword(s):

Bordetella Pertussis ◽

Nasal Carriage ◽

Interferon Γ ◽

Neutrophil Recruitment ◽

Interleukin 17 ◽

Nasal Colonization ◽

Lung Colonization ◽

Cell Induction ◽

Ifn Γ ◽

Deficient Mice

AbstractPertussis has made a spectacular rebound in countries that have switched from whole-cell (wPV) to acellular pertussis vaccines (aPV). Here, we show that, unlike wPV, aPV, while protective against lung colonization by Bordetella pertussis (Bp), did not protect BALB/c mice from nasal colonization, but instead substantially prolonged nasal carriage. aPV prevented the natural induction of nasal interleukin-17 (IL-17)-producing and interferon-γ (IFN-γ)-producing CD103+ CD44+ CD69+ CD4+-resident memory T (TRM) cells. IL-17-deficient, but not IFN-γ-deficient, mice failed to clear nasal Bp, indicating a key role of IL-17+ TRM cells in the control of nasal infection. These cells appeared essential for neutrophil recruitment, crucial for clearance of Bp tightly bound to the nasal epithelium. Transfer of IL-17+ TRM cells from Bp-infected mice to IL-17-deficient mice resulted in neutrophil recruitment and protection against nasal colonization. Thus, aPV may have augmented the Bp reservoir by inhibiting natural TRM cell induction and neutrophil recruitment, thereby contributing to the pertussis resurgence.

Download Full-text

Development of RNAseq methodologies to profile the in vivo transcriptome of Bordetella pertussis during murine lung infection

10.1101/140632 ◽

2017 ◽

Cited By ~ 1

Author(s):

Ting Wong ◽

Jesse Hall ◽

Dylan Boehm ◽

Mariette Barbier ◽

F. Heath Damron

Keyword(s):

Bordetella Pertussis ◽

Whooping Cough ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Respiratory Pathogen ◽

Cell Vaccine ◽

Bacterial Cells ◽

Murine Lung

AbstractBordetella pertussis is an obligate human respiratory pathogen that causes the disease whooping cough. A whole cell vaccine (DTP) was developed in the 1940s and was subsequently replaced in the 1990s with a protein-based subunit acellular vaccine (DTaP; tdap). Today, we are observing a resurgence of whooping cough due to evolution of the pathogen and waning vaccine immunity. The use of vaccines decreased the need for basic research on this pathogen. As a result, numerous questions on the basic pathogenesis of B. pertussis remain to be answered. Microarrays and more recently, RNA sequencing (RNAseq), have allowed the field to describe the in vitro gene expression profiles of the pathogen growing in both virulent and avirulent phases; however, no published studies have described an in vivo transcriptome of the pathogen. To address this need, we have designed and evaluated workflows to characterize the in vivo transcriptome of B. pertussis during infection of the murine lung. During our initial studies, we observed that only 0.014% of the ~100 million 2x50bp illumina reads corresponded to the pathogen, which is insufficient for analysis. Therefore, we developed a simple protocol to filter the bacteria out of the tissue homogenates and separate bacterial cells from the host tissue. RNA is then prepared, quantified, and the B. pertussis to host RNA ratio is determined. Here, we present the protocol and discuss the uses and next directions for which this RNAseq workflow can be applied. With this strategy we plan to fully characterize the B. pertussis transcriptome when the pathogen is infecting the murine lung in order to identify expressed genes that encode potential new vaccine antigens that will facilitate the development of the next generation of pertussis vaccines.

Download Full-text

Characterization of murine lung inflammation after infection with parental Bordetella pertussis and mutants deficient in adhesins or toxins.

Infection and Immunity ◽

10.1128/iai.62.7.2893-2900.1994 ◽

1994 ◽

Vol 62 (7) ◽

pp. 2893-2900 ◽

Cited By ~ 71

Author(s):

N Khelef ◽

C M Bachelet ◽

B B Vargaftig ◽

N Guiso

Keyword(s):

Bordetella Pertussis ◽

Lung Inflammation ◽

Murine Lung

Download Full-text

Antigens of Bordetella pertussis IV. Effect of Heat, Merthiolate, and Formaldehyde on Histamine-Sensitizing Factor and Protective Activity of Soluble Extracts from Bordetella pertussis

Journal of Bacteriology ◽

10.1128/jb.91.6.2175-2179.1966 ◽

1966 ◽

Vol 91 (6) ◽

pp. 2175-2179 ◽

Cited By ~ 4

Author(s):

J. Munoz ◽

B. M. Hestekin

Keyword(s):

Bordetella Pertussis ◽

Protective Activity

Download Full-text

Dose Response of Attenuated Bordetella pertussis BPZE1-Induced Protection in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00322-09 ◽

2010 ◽

Vol 17 (3) ◽

pp. 317-324 ◽

Cited By ~ 23

Author(s):

Nathalie Mielcarek ◽

Anne-Sophie Debrie ◽

Severine Mahieux ◽

Camille Locht

Keyword(s):

Bordetella Pertussis ◽

Whooping Cough ◽

Vaccine Coverage ◽

Mouse Lung ◽

High Dose ◽

Cell Mediated Immunity ◽

Lung Colonization ◽

Current Vaccine ◽

Two Parameters ◽

Dose Dependent

ABSTRACT Despite the availability of efficacious vaccines, the incidence of whooping cough is still high in many countries and is even increasing in countries with high vaccine coverage. Most severe and life-threatening pertussis cases occur in infants who are too young to be sufficiently protected by current vaccine regimens. As a potential solution to this problem, we have developed an attenuated live Bordetella pertussis vaccine strain, named BPZE1. Here, we show that after a single administration, BPZE1 induces dose-dependent protection against challenge with virulent B. pertussis in low-dose and in high-dose intranasal mouse lung colonization models. In addition, we observed BPZE1 dose-dependent antibody titers to B. pertussis antigens, as well as cell-mediated immunity, evidenced by the amounts of gamma interferon (IFN-γ) released from spleen cells upon stimulation with B. pertussis antigens. These two parameters may perhaps be used as readouts in clinical trials in humans that are currently being planned.

Download Full-text