Mucosal immunization with DTaP confers protection against Bordetella pertussis infection and cough in Sprague-Dawley rats

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis ( Bp ). The transition from a whole cell pertussis vaccine (wP; DTP) to an acellular pertussis vaccine (aP; DTaP; Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Overall, our goal was to evaluate the route of vaccination in the coughing rat model of pertussis. Immunity induced by both oral gavage (OG) and intranasal (IN) vaccination of aP in Bp challenged rats over a nine-day infection was compared to intramuscular (IM)-wP and IM-aP immunized rats that were used as positive controls. Our data demonstrate that mucosal immunization of aP resulted in production of anti- Bp IgG antibody titers similar to IM-wP and IM-aP vaccinated controls post-challenge. IN-aP also induced anti- Bp IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against Bp induced cough, while OG-aP immunization did not protect against respiratory distress. Mucosal immunization by both IN and OG administration protected against acute inflammation and decreased bacterial burden in the lung compared to mock vaccinated challenge (MVC) rats. The data presented in this study suggests that mucosal vaccination with aP can induce a mucosal immune response and provide protection against Bp challenge. This study highlights the potential benefits and uses of the coughing rat model of pertussis; however, further questions regarding waning immunity still require additional investigation.

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Mucosal immunization with DTaP confers protection against Bordetella pertussis infection and cough in Sprague-Dawley rats

10.1101/2021.06.21.449353 ◽

2021 ◽

Author(s):

Jesse Michael Hall ◽

Graham J Bitzer ◽

Megan A DeJong ◽

Jason Kang ◽

Ting Y. Wong ◽

...

Keyword(s):

Pertussis Vaccine ◽

Bordetella Pertussis ◽

Natural Infection ◽

Mucosal Immune Response ◽

Mucosal Immunization ◽

Sprague Dawley ◽

Igg Antibody ◽

Pertussis Infection ◽

Mucosal Vaccination ◽

Antibody Titers

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis (Bp). The transition from a whole cell pertussis vaccine (wP; DTP) to an acellular pertussis vaccine (aP; DTaP; Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Immunity induced by both oral gavage (OG) and intranasal (IN) vaccination of aP in Bp challenged rats over a nine-day infection was compared to intramuscular (IM)-wP and IM-aP immunized rats that were used as positive controls as IM immunization is the current route for wP and aP vaccination. Our data demonstrate that both IN and OG immunization of aP resulted in production of anti-Bp IgG antibody titers similar to IM-wP and IM-aP vaccinated controls post-challenge. IN-aP also induced anti-Bp IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against Bp induced cough, while OG-aP immunization did not protect against respiratory distress Mucosal immunization (IN-aP and OG-aP) also protected against acute inflammation and decreased bacterial burden in the lung compared to mock vaccinated challenge (MVC) rats. The data presented in this study suggests that mucosal vaccination with aP can induce a mucosal immune response and provide protection against Bp> challenge.

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Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis

npj Vaccines ◽

10.1038/s41541-019-0136-2 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 5

Author(s):

Dylan T. Boehm ◽

M. Allison Wolf ◽

Jesse M. Hall ◽

Ting Y. Wong ◽

Emel Sen-Kilic ◽

...

Keyword(s):

Immune Responses ◽

Pertussis Vaccine ◽

Bordetella Pertussis ◽

Mucosal Immunity ◽

Natural Infection ◽

Mucosal Immune Response ◽

Respiratory Pathogen ◽

Mucosal Immune Responses ◽

Optimal Protection ◽

Pro Inflammatory Cytokines

Abstract Current acellular pertussis vaccines fall short of optimal protection against the human respiratory pathogen Bordetella pertussis resulting in increased incidence of a previously controlled vaccine- preventable disease. Natural infection is known to induce a protective mucosal immunity. Therefore, in this study, we aimed to use acellular pertussis vaccines to recapitulate these mucosal immune responses. We utilized a murine immunization and challenge model to characterize the efficacy of intranasal immunization (IN) with DTaP vaccine or DTaP vaccine supplemented with curdlan, a known Th1/Th17 promoting adjuvant. Protection from IN delivered DTaP was compared to protection mediated by intraperitoneal injection of DTaP and whole-cell pertussis vaccines. We tracked fluorescently labeled DTaP after immunization and detected that DTaP localized preferentially in the lungs while DTaP with curdlan was predominantly in the nasal turbinates. IN immunization with DTaP, with or without curdlan adjuvant, resulted in anti-B. pertussis and anti-pertussis toxin IgG titers at the same level as intraperitoneally administered DTaP. IN immunization was able to protect against B. pertussis challenge and we observed decreased pulmonary pro-inflammatory cytokines, neutrophil infiltrates in the lung, and bacterial burden in the upper and lower respiratory tract at day 3 post challenge. Furthermore, IN immunization with DTaP triggered mucosal immune responses such as production of B. pertussis-specific IgA, and increased IL-17A. Together, the induction of a mucosal immune response and humoral antibody-mediated protection associated with an IN administered DTaP and curdlan adjuvant warrant further exploration as a pertussis vaccine candidate formulation.

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Development and Analytical Validation of an Immunoassay for Quantifying Serum Anti-Pertussis Toxin Antibodies Resulting from Bordetella pertussis Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00248-09 ◽

2009 ◽

Vol 16 (12) ◽

pp. 1781-1788 ◽

Cited By ~ 26

Author(s):

Sandra L. Menzies ◽

Vijay Kadwad ◽

Lucia C. Pawloski ◽

Tsai-Lien Lin ◽

Andrew L. Baughman ◽

...

Keyword(s):

Pertussis Toxin ◽

Bordetella Pertussis ◽

Collaborative Study ◽

World Health ◽

Enzyme Linked Immunosorbent Assay ◽

Analytical Validation ◽

Igg Antibody ◽

Pertussis Infection ◽

Validation Parameters ◽

Health Organization

ABSTRACT Adequately sensitive and specific methods to diagnose pertussis in adolescents and adults are not widely available. Currently, no Food and Drug Administration-approved diagnostic assays are available for the serodiagnosis of Bordetella pertussis. Since concentrations of B. pertussis-specific antibodies tend to be high during the later phases of disease, a simple, rapid, easily transferable serodiagnostic test was developed. This article describes test development, initial evaluation of a prototype kit enzyme-linked immunosorbent assay (ELISA) in an interlaboratory collaborative study, and analytical validation. The data presented here demonstrate that the kit met all prespecified criteria for precision, linearity, and accuracy for samples with anti-pertussis toxin (PT) immunoglobulin G (IgG) antibody concentrations in the range of 50 to 150 ELISA units (EU)/ml, the range believed to be most relevant for serodiagnosis. The assay met the precision and linearity criteria for a wider range, namely, from 50 to 200 EU/ml; however, the accuracy criterion was not met at 200 EU/ml. When the newly adopted World Health Organization International Standard for pertussis antiserum (human) reference reagent was used to evaluate accuracy, the accuracy criteria were met from 50 to 200 international units/ml. In conclusion, the IgG anti-PT ELISA met all assay validation parameters within the range considered most relevant for serodiagnosis. This ELISA was developed and analytically validated as a user-friendly kit that can be used in both qualitative and quantitative formats. The technology for producing the kit is transferable to public health laboratories.

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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.

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Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection

Vaccines ◽

10.3390/vaccines8040647 ◽

2020 ◽

Vol 8 (4) ◽

pp. 647

Author(s):

Catherine B. Blackwood ◽

Emel Sen-Kilic ◽

Dylan T. Boehm ◽

Jesse M. Hall ◽

Melinda E. Varney ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Immune Responses ◽

Bordetella Pertussis ◽

Respiratory Pathogens ◽

Igg Antibodies ◽

Pertussis Infection ◽

Lung Weight ◽

Whole Cell ◽

Mucosal Vaccination ◽

Serum Igg

Whole cell vaccines are frequently the first generation of vaccines tested for pathogens and can inform the design of subsequent acellular or subunit vaccines. For respiratory pathogens, administration of vaccines at the mucosal surface can facilitate the generation of a localized mucosal immune response. Here, we examined the innate and vaccine-induced immune responses to infection by two respiratory pathogens: Bordetella pertussis and Pseudomonas aeruginosa. In a model of intranasal administration of whole cell vaccines (WCVs) with the adjuvant curdlan, we examined local and systemic immune responses following infection. These studies showed that intranasal vaccination with a WCV led to a reduction of the bacterial burden in the airways of animals infected with the respective pathogen. However, there were unique changes in the cytokines produced, cells recruited, and inflammation at the site of infection. Both mucosal vaccinations induced antibodies that bind the target pathogen, but linear regression and principal component analysis revealed that protection from these pathogens is not solely related to antibody titer. Protection from P. aeruginosa correlated to a reduction in lung weight, blood lymphocytes and neutrophils, and the cytokines IL-6, TNF-α, KC/GRO, and IL-10, and promotion of serum IgG antibodies and the cytokine IFN-γ in the lung. Protection from B. pertussis infection correlated strongly with increased anti-B-pertussis serum IgG antibodies. These findings reveal valuable correlates of protection for mucosal vaccination that can be used for further development of both B. pertussis and P. aeruginosa vaccines.

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A population-based Study of Recurrent Symptomatic Bordetella pertussis Infections in Children in California, 2010–2015

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.162 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S68-S68

Author(s):

Lauren Platt ◽

Melissa Thun ◽

Kathleen Harriman ◽

Kathleen Winter

Keyword(s):

Immune Response ◽

Bordetella Pertussis ◽

Natural Infection ◽

Population Based ◽

Case Definition ◽

Inclusion Criteria ◽

Pertussis Infection ◽

Population Based Study ◽

Initial Infection ◽

Sterilizing Immunity

Abstract Background Natural infection with Bordetella pertussis is thought to result in 4–20 years of immunity against subsequent symptomatic pertussis infection. However, these estimates are based on studies in unvaccinated or whole-cell vaccinated children. We conducted a population-based study of pertussis infection and reinfection during a 5-year period in California in an exclusively acellular-pertussis vaccinated cohort. Methods California surveillance data were reviewed to identify all children with two reported incidents of pertussis with symptom onset from January 1, 2010 through December 31, 2015. Case investigation reports were reviewed and children with at least two episodes of symptomatic pertussis infection that met the case definition were included. Results Of 26,259 pertussis cases reported in children <18 years, 27 children met the inclusion criteria. Recurrent cases occurred among children of all ages, and the median age for the first and second pertussis episodes were 3.5 years (range, 1.3 months-14 years) and 6.5 years (range, 5.2 months–16.3 years) respectively. The median duration of time between initial infection and reinfection was 1.3 years (range, 2.9 months–4.4 years). Twenty-one children (78%) had received ≥3 doses of DTaP vaccine at the time of their first pertussis infection, 1 (4%) had received 1 dose, and 5 (19%) were unvaccinated. Conclusion Recurrent cases of pertussis infection are very rare. Contrary to previous reports that natural infection with B. pertussis results in 4–20 years of sterilizing immunity, we demonstrate that symptomatic reinfection with pertussis can occur as soon as 89 days following the first infection. More research is needed to understand the immune response to B. pertussis infection in children vaccinated with acellular-pertussis vaccines. Disclosures All authors: No reported disclosures.

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Variation of serotype in strains of Bordetella pertussis

Journal of Hygiene ◽

10.1017/s0022172400024165 ◽

1974 ◽

Vol 73 (2) ◽

pp. 305-310 ◽

Cited By ~ 21

Author(s):

T. N. Stanbridge ◽

N. W. Preston

Keyword(s):

Mutation Rate ◽

Pertussis Vaccine ◽

Bordetella Pertussis ◽

High Frequency ◽

Agar Medium ◽

Blood Agar ◽

Pertussis Infection

SUMMARYThe four main serotypes of Bordetella pertussis (1, 2, 3; 1, 2; 1, 3; 1) undergo spontaneous variation involving loss or gain of antigen 2 or antigen 3. By serial subculture from single colonies on charcoal-blood-agar medium, we have detected loss-mutations from type 1, 2, 3 to 1, 2 or 1, 3, and from type 1, 2 to type 1. Likewise we have found gain-mutations from type 1 to 1, 2 or 1, 3, and from 1, 2 to 1, 2, 3.These mutations apparently occur with a high frequency in some strains. Other strains have a lower mutation-rate and are more stable antigenically. We have not detected, by this method, either gain- or loss-mutations from the type 1, 3 strains that we have tested.These findings offer an explanation for the changes in serotype that occur during the course of a pertussis infection in the child and in the marmoset. They also constitute a warning on the possible antigenic instability of laboratory strains, especially relevant in the production, absorption and testing of diagnostic antisera and in the preparation of pertussis vaccine.

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Acellular Pertussis Vaccine Components: Today and Tomorrow

Vaccines ◽

10.3390/vaccines8020217 ◽

2020 ◽

Vol 8 (2) ◽

pp. 217 ◽

Cited By ~ 3

Author(s):

Kalyan K. Dewan ◽

Bodo Linz ◽

Susan E. DeRocco ◽

Eric T. Harvill

Keyword(s):

Respiratory Infection ◽

Pertussis Vaccine ◽

Bordetella Pertussis ◽

Acute Respiratory Infection ◽

Natural Infection ◽

Clinical Implications ◽

Disease Epidemiology ◽

Vaccination Strategies ◽

Before And After ◽

Control Disease

Pertussis is a highly communicable acute respiratory infection caused by Bordetella pertussis. Immunity is not lifelong after natural infection or vaccination. Pertussis outbreaks occur cyclically worldwide and effective vaccination strategies are needed to control disease. Whole-cell pertussis (wP) vaccines became available in the 1940s but have been replaced in many countries with acellular pertussis (aP) vaccines. This review summarizes disease epidemiology before and after the introduction of wP and aP vaccines, discusses the rationale and clinical implications for antigen inclusion in aP vaccines, and provides an overview of novel vaccine strategies aimed at better combating pertussis in the future.

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A Bordetella pertussis-antitestek szeroprevalenciája magyarországi felnőttekben

Orvosi Hetilap ◽

10.1556/650.2018.30941 ◽

2018 ◽

Vol 159 (13) ◽

pp. 503-510

Author(s):

Péter Torzsa ◽

Devadiga Raghavendra ◽

Monica Tafalla

Keyword(s):

Bordetella Pertussis ◽

Whooping Cough ◽

Acute Respiratory Tract Infection ◽

Enzyme Linked Immunosorbent Assay ◽

Igg Antibody ◽

Recent Infection ◽

Pertussis Infection ◽

Young Infants ◽

One Year ◽

Antibody Levels

Abstract: Introduction: Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis that is characterized by a chronic, severe cough. The optimum immunization schedule for pertussis is unclear, so these vary by countries. Aim: To estimate the seroprevalence of pertussis in adults in Hungary. Method: Serum anti-pertussis toxin immunoglobulin G (anti-PT IgG) antibody levels were analyzed using enzyme-linked immunosorbent assay in adults in general practitioners’ practices during one year. Sera were classified following manufacturer’s instructions as: strongly indicative of current/recent infection (≥1.5 optical density [OD] units); indicative of current/recent infection (≥1.0 OD units); seropositive (>0.3 OD units); or seronegative (≤0.3 OD units). Results: 1999 adults (60.6% female; mean age 47.4 ± 17.7 years) were included. 14.8% were seropositive, 1.1% were indicative of current/recent infection, and 0.1% were strongly indicative of current/recent infection. Conclusions: 85.2% of the subjects were seronegative and therefore susceptible to pertussis infection. Approximately 1% was suspicious of current/recent pertussis infection, potentially transmissible to susceptible young infants. Vaccination of adults is a key way to indirectly protect infants. Orv Hetil. 2018; 159(13): 503–510.

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