Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children

Siber, George R.; Thakrar, Nisha; Yancey, Betti Ann; Herzog, Lynn W.; Todd, Charles W.; Cohen, Nadine D.; Sekura, Ronald D.; Lowe, Charles U.

doi:10.1016/0264-410x(91)90289-i

Cited by 32 publications

(10 citation statements)

References 18 publications

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“…However, inactivation of microbes with H 2 O 2 (as well as other oxidizing agents such as superoxide and nitric oxide) represents a key element of the innate mammalian immune system and functions in endosomal compartments to inactivate intracellular pathogens 12 . In addition, H 2 O 2 has also been used to detoxify pertussis toxin 13 . In these current studies we have used three unrelated virus model systems to show that H 2 O 2 -based vaccines can protect against chronic or lethal viral infection, and we believe that this approach represents a new concept in vaccine development.…”

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confidence: 99%

Development of a new hydrogen peroxide–based vaccine platform

Amanna

Raué

Slifka

2012

Nat Med

104

127

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Safe and effective vaccines are crucial for maintaining public health and reducing the global burden of infectious disease. Here we introduce a new vaccine platform that uses hydrogen peroxide (H2O2) to inactivate viruses for vaccine production. H2O2 rapidly inactivates both RNA and DNA viruses with minimal damage to antigenic structure or immunogenicity and is a highly effective method when compared with conventional vaccine inactivation approaches such as formaldehyde or β-propiolactone. Mice immunized with H2O2-inactivated lymphocytic choriomeningitis virus (LCMV) generated cytolytic, multifunctional virus-specific CD8+ T cells that conferred protection against chronic LCMV infection. Likewise, mice vaccinated with H2O2-inactivated vaccinia virus or H2O2-inactivated West Nile virus showed high virus-specific neutralizing antibody titers and were fully protected against lethal challenge. Together, these studies demonstrate that H2O2-based vaccines are highly immunogenic, provide protection against a range of viral pathogens in mice and represent a promising new approach to future vaccine development.

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mentioning

confidence: 99%

Development of a new hydrogen peroxide–based vaccine platform

Amanna

Raué

Slifka

2012

Nat Med

104

127

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“…3 Phase 1 and phase 2 studies showed that pertussis toxin treated with H 2 O 2 (PTox) was safe and immunogenic in adults 4 and children. 5,6 An open study of clinical pertussis in children receiving the same vaccine and an age-matched nonvaccinated control group showed that the vaccine decreased the risk of pertussis in the vaccinees. 7 On the basis of these studies, a randomized, double-blind, placebocontrolled trial of PTox (as a component of DTPTox) involving 3450 infants was conducted in Gö teborg: children in the control group received DT.…”

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confidence: 99%

Immunologic and Epidemiologic Experience of Vaccination With a Monocomponent Pertussis Toxoid Vaccine

et al. 2001

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ABSTRACT. Pertussis re-emerged in Sweden with a cumulative incidence of about 60% during the first 10 years of life, when the locally produced cellular vaccine lost its efficacy around 1970 and general vaccination was discontinued in 1979. The epidemiology, clinical features, and immunology of pertussis and a monocomponent pertussis toxoid vaccine were studied in Gö teborg, Sweden.After phase 1 and 2 studies, a randomized, doubleblind, placebo-controlled trial of pertussis toxoid (PTox), compounded with diphtheria and tetanus toxoids, was administered to 3450 children according to the Swedish schedule at 3, 5, and 12 months of age. After a mean follow-up of 18 months, the efficacy was 71% overall and 75% in household contacts, respectively. A statistically significant correlation was found between the level of PTox-induced antibodies and protection against pertussis. As observed with cellular and with multicomponent acellular vaccines, PTox reduced the severity of disease and the percent of children with positive cultures. Furthermore, vaccination reduced the transmission of Bordetella pertussis to household contacts in the vaccinees compared with the controls who received only diphtheria and tetanus toxoids. Patients with culture-verified Bordetella parapertussis infection reacted with antibodies to pertactin and to filamentous hemagglutinin but not to pertussis toxin, and some subsequently developed pertussis. The antibody responses of patients with pertussis to the surface polysaccharides of B pertussis and to B parapertussis were cross-reactive serologically. Serosurveys showed that only antibodies to pertussis toxin were related to the occurrence of pertussis in the general population: antibodies to filamentous hemagglutinin and pertactin were probably stimulated by antigens of other bacteria as well as Bordetellae.Mass vaccination of Gö teborg children born in the 1990s was started in 1995. In February 1999, about 55% had been vaccinated and both B pertussis and pertussis decreased significantly in individuals of all ages (herd immunity). Similar to diphtheria, PTox-induced immunity to pertussis occurs both on an individual and community basis.The apparent greater efficacy of multicomponent acellular pertussis vaccines compared with monocomponent PTox was proposed to be an artifact created when the diagnosis of pertussis was made by the serologic criteria of the World Health Organization only. Our conclusion is that PTox is both an essential and alone sufficient antigen in acellular pertussis vaccines. Pediatrics 2001; 108(6). URL: http://www.pediatrics.org/cgi/content/full/ 108/6/e115; pertussis, pertussis toxoid, vaccine.

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“…(i) Human anti-PT IgG assays. Mouse sera were assayed for detection of human anti-PT antibody concentrations by methods modified from those previously described by Siber et al (59). Briefly, 96-well plates (Dynatech Immulon 2; Dynatech, Alexandria, Va.) were coated with purified PT (1.0 g/ml) obtained from the MPHBL.…”

Section: Methodsmentioning

confidence: 99%

“…The anti-PT IgG antibody concentrations for the A70 standard were determined by the Zollinger method as previously described (59,63). By using the Center for Biologics Evaluation and Review (CBER) pertussis reference antiserum (lot 3), 1 g/ml was determined to be equivalent to 10 CBER U/ml for PT IgG.…”

Section: Methodsmentioning

confidence: 99%

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Protective Effects of Pertussis Immunoglobulin (P-IGIV) in the Aerosol Challenge Model

Bruss

Siber

1999

Clin Diagn Lab Immunol

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Pertussis in infants is often severe, resulting in prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease unless administered during the catarrhal phase. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, may be beneficial. This study uses the aerosol challenge model to further examine the protective effects of P-IGIV, a new intravenous immunoglobulin product, which has high levels of pertussis toxin antibodies. P-IGIV was prepared as a 4% immunoglobulin G (IgG) solution from the pooled donor plasma from donors immunized with inactivated pertussis toxoid. The IgG pertussis toxin antibody concentration in P-IGIV is >7-fold higher than conventional intravenous immunoglobulin products. In the aerosol challenge model, P-IGIV-treated mice exhibited a dose-dependent decrease in mortality when monitored for 28 days postchallenge. P-IGIV in doses of 2,800, 1,400, and 350 mg/kg significantly reduced mortality compared to saline (P < 0.01)- and human IGIV (P < 0.01)-treated controls. The 50% protective dose of pertussis toxin antibodies in P-IGIV was 147 μg/ml. Recovery of weight gain and normalization of leukocyte counts occurred in all P-IGIV-treated groups but did not exhibit dose-dependent characteristics. Even after 7 days of infection, P-IGIV reversed the effects of pertussis in mice. This study provides further evidence that pertussis toxin antibodies not only play a role in passive protection but can also reverse symptoms of established disease in mice. We feel that P-IGIV deserves further evaluation in children hospitalized with severe pertussis.

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Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children

Cited by 32 publications

References 18 publications

Development of a new hydrogen peroxide–based vaccine platform

Development of a new hydrogen peroxide–based vaccine platform

Immunologic and Epidemiologic Experience of Vaccination With a Monocomponent Pertussis Toxoid Vaccine

Protective Effects of Pertussis Immunoglobulin (P-IGIV) in the Aerosol Challenge Model

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