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Molecular basis of the adjuvant properties of Bordetella pertussis in combination with Streptococcus pneumoniae protein antigens


Streptococcus pneumoniae (pneumococcus) is a major cause of pneumonia, meningitis and sepsis in children worldwide. Recent estimates calculate that between 700000 and 1 million people die annually by pneumococcal infections around the world. The Pneumococcal surface protein A (PspA) is a well characterized antigen, which confers protection in animal models, representing a good alternative to the current conjugated vaccines. The induction of protective immune response directed the PspA in animal models has been described, but few inexpensive adjuvants for the composition of a subunit vaccine, were proposed until today. Recently, our group has tested the cellular pertussis vaccine (wP) as an adjuvant, in combination with PspA. Nasal immunization of mice BALB/c with a combination of PspA from clade 5 (PspA5) with wP or wPlow-a cellular pertussis vaccine containing low levels of LPS-conferred protection against a lethal respiratory challenge with S. pneumoniae. Both PspA5 - wP and PspA5-wPlow vaccines induced higher levels of systemic and mucosal anti-PspA5antibodies and suggesting that the LPS is not essential for the adjuvant activity observed. Thus, other components of B. pertussis may be acting as adjuvants in this model. This project aims to characterize the molecular and immunological bases of adjuvant activity of B. pertussis alone and when administered in combination with pneumococal antigens. To this end we propose the use of B. pertussis mutant strains with deficiency in one or more components with known immunomodulatory properties, as well as the use of purified components such as LPS, MPLA and the pertussis toxin. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SALCEDO-RIVILLAS, CAROLINA; DEBRIE, ANNE-SOPHIE; MIYAJI, ELIANE NAMIE; FERREIRA, JR., JORGE M. C.; RAW, ISAIAS; LOCHT, CAMILLE; HO, PAULO L.; MIELCAREK, NATHALIE; OLIVEIRA, MARIA LEONOR S. Pertussis Toxin Improves Immune Responses to a Combined Pneumococcal Antigen and Leads to Enhanced Protection against Streptococcus pneumoniae. Clinical and Vaccine Immunology, v. 21, n. 7, p. 972-981, JUL 2014. Web of Science Citations: 1.

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