A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis

Greco, Donato; Salmaso, Stefania; Mastrantonio, Paola; Giuliano, Marina; Tozzi, Alberto Eugenio; Anemona, Alessandra; Atti, Marta Luisa Ciofi degli; Giammanco, Anna; Panei, Pietro; Blackwelder, William C.; Klein, David L.; Wassilak, Steven G.F.

doi:10.1056/nejm199602083340601

Cited by 644 publications

(416 citation statements)

References 32 publications

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“…Inactivated PT is a component of most Pas, and it is known that booster immunization of children with an acellular pertussis vaccine enhanced Th2 cytokine production and serum IgE responses against PT (50). Circulating IgE antibodies against PT have also been found after primary immunization with Pa with or without a subsequent Pa or Pw booster (11,17,42). Furthermore, B. pertussis infection is known to modulate allergen priming and exacerbates the severity of allergen-driven pathology in a murine model (8); however, Th1-inducing vaccines (Pw) protect against this (7).…”

Section: Discussionmentioning

confidence: 99%

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

Ennis

Cassidy

Mahon

2005

Clin Vaccine Immunol

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The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of allergic asthma. Groups of mice were immunized with Pa, infected with B. pertussis, and/or sensitized to ovalbumin. Immunological, pathological, and physiological changes were measured to assess the impact of immunization on immune deviation and airway function. We demonstrate that immunization did not enhance ovalbumin-specific serum immunoglobulin E production. Histopathological examination revealed that immunization reduced the severity of airway pathology associated with sensitization in the context of infection and decreased bronchial hyperreactivity upon methacholine exposure of infected and sensitized mice. These data demonstrate unequivocally the benefit of Pa immunization to health and justify selection of Pa in mass vaccination protocols. In the absence of infection, the Pa used in this study enhanced the interleukin-10 (IL-10) and IL-13 responses and influenced airway hyperresponsiveness to sensitizing antigen; however, these data do not suggest that Pa contributes to childhood asthma overall. On the contrary, wild-type virulent B. pertussis is still circulating in most countries, and our data suggest that the major influence of Pa is to protect against the powerful exacerbation of asthma-like pathology induced by B. pertussis.

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Section: Discussionmentioning

confidence: 99%

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

Ennis

Cassidy

Mahon

2005

Clin Vaccine Immunol

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“…or s.c. administration in mice appears to correlate well with the response to i.m. immunization of DTaP in humans (Greco et al, 1996;Gustafsson et al, 1996;Olin et al, 1997). Our rationale for choosing the s.c. route of administration was based on studies investigating the efficacy of aP vaccines in mice, which delivered 0.2-0.25 standard human dose of vaccine via the s.c. route (Barnard et al, 1996;van den Berg et al, 2000;Donnelly et al, 2001).…”

Section: Igg Titres In the Serum Of Immunized Micementioning

confidence: 99%

Parenteral immunization of mice with a genetically inactivated pertussis toxin DNA vaccine induces cell-mediated immunity and protection

Fry

Chen

Daggard

et al. 2008

Journal of Medical Microbiology

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The immunogenicity and protective efficacy of a DNA vaccine encoding a genetically inactivated S1 domain of pertussis toxin was evaluated using a murine respiratory challenge model of Bordetella pertussis infection. It was found that mice immunized via the intramuscular route elicited a purely cell-mediated immune response to the DNA vaccine, with high levels of gamma interferon (IFN-c) and interleukin (IL)-2 detected in the S1-stimulated splenocyte supernatants and no serum IgG. Despite the lack of an antibody response, the lungs of DNA-immunized mice were cleared of B. pertussis at a significantly faster rate compared with mock-immunized mice following an aerosol challenge. To gauge the true potential of this S1 DNA vaccine, the immune response and protective efficacy of the commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccine were included as the gold standard. Immunization with DTaP elicited a typically strong T-helper (Th)2-polarized immune response with significantly higher titres of serum IgG than in the DNA vaccine group, but a relatively weak Th1 response with low levels of IFN-c and IL-2 detected in the supernatants of antigen-stimulated splenocytes. DTaP-immunized mice cleared the aerosol challenge more efficiently than DNA-immunized mice, with no detectable pathogen after day 7 post-challenge.

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“…In contrast, genetically detoxified PT mutants -including PT-9K/129G, that lacks enzymatic activity -retain the functional and immunological properties of wild-type PT [9]. PT-9K/129G was shown to be safe and immunogenic as a component of a DTaP vaccine evaluated in two large Phase III efficacy trial in infants [10,11]. Furthermore, PT-9K/129G induced higher anti-PT antibody titres and longer lasting protection when compared with a vaccine containing chemically detoxified PT.…”

Section: Introductionmentioning

confidence: 99%

Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

Misiak

Leuzzi

Allen

et al. 2017

Vaccine

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a b s t r a c tA resurgence of whooping cough (pertussis) has been observed in recent years in a number of developed countries, despite widespread vaccine coverage. Although the exact reasons of the recurrence of pertussis are not clear, there are a number of potential causes, like antigenic variation in the circulating strains of Bordetella pertussis, changes in surveillance and diagnostic tools, and potential differences in protection afforded by current acellular pertussis (aP) vaccines compared to more reactogenic whole cell (wP) vaccines, which they replaced. Studies in animal models have shown that induction of cellular as well as humoral immune responses are key to conferring effective and long lasting protection against B. pertussis. wP vaccines induce robust Th1/Th17 responses, which are associated with good protection against lung infection. In contrast, aP vaccines induce mixed Th2/Th17 responses. One research option is to modify current aP vaccines with the intention of inducing protective T cell responses, without compromising on their low reactogenicity profile. Here we found that formulation of an aP vaccine with a novel adjuvant based on a Toll-like receptor 7 agonist (TLR7a) adsorbed to aluminum hydroxide (alum) enhanced B. pertussis-specific Th1 and Th17 responses and serum IgG2a/b antibodies, which had greater functional capacity than those induced by aP formulated with alum alone. Furthermore, addition of a TLR7a enhanced the protective efficacy of the aP vaccine against B. pertussis aerosol challenge; protection was comparable to that of a wP vaccine. These findings suggest that alum-TLR7a is a promising adjuvant for clinical development of next generation pertussis vaccines.

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A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis

Abstract: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.

Cited by 644 publications

References 32 publications

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

Parenteral immunization of mice with a genetically inactivated pertussis toxin DNA vaccine induces cell-mediated immunity and protection

Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

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