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

Abstract

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.

Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection

“…Other conserved Sp proteins, such as pneumococcal surface antigen A (PsaA), pneumolysin, pneumolysoid PdT, and histidine triad proteins have been used with potent adjuvants as subunit vaccines that protect mice against pneumonia. 24, 26, 27, 29, 33 Although these studies have not directly tested the role of memory Th17 cells in protection against pneumonia, these findings together with our results support the notion that Th17-inducing conserved Sp protein antigens might be vaccine candidates capable of conferring broad protection by inducing strong memory Th17 responses in the lungs.…”

“…23 Repeated immunizations with killed whole cell vaccines or conserved proteins with potent experimental adjuvants (pertussis toxin) confer protection against lung infections by different serotype strains. 24-29 The mechanisms of cross-protection against pneumonia remain controversial and undefined. Depletion of B cells, CD4 + or CD8 + T cells after immunization did not abrogate protection.…”

“…25, 27 On the other hand, immunization of μMT mice with conserved Sp proteins/adjuvant failed to protect against pneumonia induced by heterologous strains, suggesting a role for B cells/antibodies. 29 …”

Vesículas de Membrana Externa (OMV) de >i<Neisseria lactamia>/i<: Processo de Obtenção e Avaliação do Potencial Adjuvante

“…A análise morfológica se fez necessária neste projeto, pois de acordo com Claassen et al (Claassen et al, 1996), em um contexto imunológico utilizando OMV como antígeno vacinal, as proteínas de membrana externa (OMP) precisam ser apresentadas em uma estrutura de membrana com conformação adequada. (Ferreira et al, 2009;Moreno et al, 2010;Oliveira et al, 2010;Salcedo-Rivillas et al, 2014). (Oliveira et al, 2010;Salcedo-Rivillas et al, 2014).…”

“…(Ferreira et al, 2009;Moreno et al, 2010;Oliveira et al, 2010;Salcedo-Rivillas et al, 2014). (Oliveira et al, 2010;Salcedo-Rivillas et al, 2014). Desse modo, a fim de contribuir para discussão deste trabalho, os resultados de sobrevivência foram considerados válidos para a estatística, apesar destes animais sobreviventes apresentarem-se debilitados.…”