Characterization of the carbohydrate binding and ADP-ribosyltransferase activities of chemically detoxified pertussis toxins

Oh, Hokyung; Kim, Byoung Guk; Nam, Kyung Tak; Hong, Seung Hwa; Ahn, Do-Hee; Choi, Gi Sub; Kim, Hyungjin; Hong, Jin Tae; Ahn, Byung Yoon

doi:10.1016/j.vaccine.2013.04.060

Cited by 12 publications

(16 citation statements)

References 15 publications

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“…Increasing concentrations of formaldehyde can differently affect the enzymatic and carbohydrate-binding activities, as well as the presence of native epitopes (52). In addition, reversion of the formaldehyde effects, mainly with respect to the carbohydrate-binding activity, has been observed (53). These studies highlighted the importance of achieving a balance between low toxicity and immunogenicity when developing PT-containing pertussis vaccines.…”

Section: Discussionmentioning

confidence: 97%

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Pertussis Toxin Improves Immune Responses to a Combined Pneumococcal Antigen and Leads to Enhanced Protection against Streptococcus pneumoniae

Salcedo-Rivillas

Debrie

Miyaji

et al. 2014

Clin. Vaccine Immunol.

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Pneumococcal surface protein A (PspA) is a candidate antigen for the composition of protein-based vaccines against Streptococcus pneumoniae. While searching for efficient adjuvants for PspA-based vaccines, our group has described the potential of combining PspA with the whole-cell pertussis vaccine (wP). When given to mice through the nasal route, a formulation composed of PspA from clade 5 (PspA5) and wP (PspA5-wP) induced high levels of antibodies and protection against challenges with different pneumococcal strains. PspA5-wP also induced the secretion of interleukin 17 (IL-17) by splenocytes and the infiltration of leukocytes in the lungs after challenge. Here, we show that protection against a pneumococcal invasive challenge was completely abrogated in MT ؊/؊ mice, which are deficient in the maturation of B cells, illustrating the importance of antibodies in the survival elicited by the PspA5-wP vaccine. Moreover, passive immunization showed that IgG purified from the sera of mice immunized with PspA5-wP conferred significant protection to naive mice, whereas the respective F(ab=) 2 did not. Additionally, in vivo depletion of complement abolished protection against the pneumococcal challenge. The combination of PspA5 with wild-type or mutant Bordetella pertussis strains or with purified components showed that the pertussis toxin (PT)-containing formulations induced the highest levels of antibodies and protection. This suggests that the adjuvant activity of wP in the PspA5 model is mediated at least in part by PT. The sera from mice immunized with such formulations displayed high IgG binding and induction of complement deposition on the pneumococcal surface in vitro, which is consistent with the in vivo results.

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Section: Discussionmentioning

confidence: 97%

“…Several studies have shown the effect of formaldehyde treatment on PT structure and activity (52,53). Increasing concentrations of formaldehyde can differently affect the enzymatic and carbohydrate-binding activities, as well as the presence of native epitopes (52).…”

Section: Discussionmentioning

confidence: 99%

Pertussis Toxin Improves Immune Responses to a Combined Pneumococcal Antigen and Leads to Enhanced Protection against Streptococcus pneumoniae

Salcedo-Rivillas

Debrie

Miyaji

et al. 2014

Clin. Vaccine Immunol.

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show abstract

Section: Discussionunclassified

“…Vários estudos mostraram o efeito deste tratamento na estrutura e atividade da PT (Fowler, Xing, 2003;Oh, Kim, 2013). Diferentes concentrações de formaldeído podem afetar diferentemente a atividade enzimática ou de ligação a carboidratos e a presença de epítopos nativos (Fowler, Xing et al, 2003;Oh, Kim et al, 2013). Além disso, reversão dos efeitos do formaldeído em vacinas pertussis celulares, principalmente com relação à capacidade de ligação a carboidratos exercida pela PT, foi observada (Oh, Kim et al, 2013 Diferentes estudos mostram a importância da indução de IgG2a para a resposta imune protetora contra PspA, pela maior capacidade de fixar complemento (Arulanandam, Lynch et al, 2001; O papel dos anticorpos na proteção conferida pelas vacinas compostas por PspA é bastante conhecido.…”

Section: Discussionunclassified

“…Diferentes concentrações de formaldeído podem afetar diferentemente a atividade enzimática ou de ligação a carboidratos e a presença de epítopos nativos (Fowler, Xing et al, 2003;Oh, Kim et al, 2013). Além disso, reversão dos efeitos do formaldeído em vacinas pertussis celulares, principalmente com relação à capacidade de ligação a carboidratos exercida pela PT, foi observada (Oh, Kim et al, 2013 Diferentes estudos mostram a importância da indução de IgG2a para a resposta imune protetora contra PspA, pela maior capacidade de fixar complemento (Arulanandam, Lynch et al, 2001; O papel dos anticorpos na proteção conferida pelas vacinas compostas por PspA é bastante conhecido. Anticorpos anti-PspA são capazes de reverter a inibição da deposição de complemento na superfície da bactéria, exercida pela proteína, levando à fagocitose por macrófagos in vitro (Mukerji, Mirza, 2012;Ren, Li et al, 2012).…”

Section: Discussionunclassified

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Desenvolvimento de vacinas proteicas contra Streptococcus pneumoniae: caracterização dos componetes adjuvantes da vacina celular pertussis e análise de novas combinações vacinais.

Rivillas¹

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Differences in epitope‐specific antibodies to pertussis toxin after infection and acellular vaccinations

et al. 2020

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Objectives Pertussis toxin (PT) is a component of all acellular pertussis vaccines. PT must be detoxified to be included in acellular vaccines, which results in conformational changes in the functional epitopes of PTs. Therefore, induced epitope‐specific antibodies to PT may vary after vaccinations or natural infections, and this information could reveal biomarkers implicated for protection and successful immunisation. Methods Pertussis toxin epitope‐specific antibodies in sera from 152 vaccinated children and 72 serologically confirmed patients were tested with a blocking ELISA, based on monoclonal antibodies that target protective PT epitopes. Results All study groups induced considerable antibody titres to subunit 1 (S1). Of interest, S3 7E10‐specific antibodies were present in patients, but not after vaccinations (P < 0.001). The impact of glutaraldehyde treatment of PT was visible on epitope 1D7 (S1), whereas epitopes 1B7 (S1) and 10D (S1) were more preserved. Antibodies to these epitopes were higher after three primary vaccine doses than after a single booster dose. Conclusion The high amount of 7E10‐specific antibodies in patients suggests this epitope might be functionally relevant in protection. The overall characteristics of epitope‐specific antibodies are influenced by infection or vaccination background, by the used detoxification method of PT and by the amount of the toxin used in immunisation.

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Characterization of the carbohydrate binding and ADP-ribosyltransferase activities of chemically detoxified pertussis toxins

Cited by 12 publications

References 15 publications

Pertussis Toxin Improves Immune Responses to a Combined Pneumococcal Antigen and Leads to Enhanced Protection against Streptococcus pneumoniae

Pertussis Toxin Improves Immune Responses to a Combined Pneumococcal Antigen and Leads to Enhanced Protection against Streptococcus pneumoniae

Desenvolvimento de vacinas proteicas contra Streptococcus pneumoniae: caracterização dos componetes adjuvantes da vacina celular pertussis e análise de novas combinações vacinais.

Differences in epitope‐specific antibodies to pertussis toxin after infection and acellular vaccinations

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