Date Published: January 19, 2017
Publisher: Public Library of Science
Author(s): Rafaella O. Tostes, Tasson C. Rodrigues, Josefa B. da Silva, Alessandra S. Schanoski, Maria Leonor S. Oliveira, Eliane N. Miyaji, Daniela Flavia Hozbor.
A promising alternative vaccine candidate to reduce the burden of pneumococcal diseases is the protein antigen PspA (Pneumococcal surface protein A). Since concomitant colonization with two or more pneumococcal strains is very common in children, we aimed to determine if immunization with PspA would be able to control co-colonization. We evaluated nasal immunization with recombinant PspA (rPspA) in a model of co-colonization with two strains expressing different PspAs. Mice were immunized intranasally with rPspAs from clades 1 to 4 (rPspA1, rPspA2, rPspA3 or rPspA4) using whole-cell pertussis vaccine (wP) as adjuvant. Mice were then challenged with a mixture of two serotype 6B isolates St491/00 (PspA1) and St472/96 (PspA4). Immunization with rPspA1+wP and rPspA4+wP reduced colonization with both strains and the mixture of rPspA1+rPspA4+wP induced greater reduction than a single antigen. Immunization rPspA1+rPspA4+wP also reduced colonization when challenge experiments were performed with a mixture of isolates of serotypes 6B (PspA3) and 23F (PspA2). Furthermore, none of the tested formulations led to a pronounced increase in colonization of one isolate over the other, showing that the vaccine strategy would not favor replacement. Interestingly, the adjuvant wP by itself already led to some reduction in pneumococcal colonization, indicating the induction of non-specific immune responses. Anti-rPspA IgG was observed in serum, nasal wash (NW) and bronchoalveolar lavage fluid (BALF) samples, whereas animals inoculated with formulations containing the adjuvant wP (with or without rPspA) showed higher levels of IL-6 and KC in NW and increase in tissue macrophages, B cells and CD4+T cells in BALF.
Streptococcus pneumoniae is part of the nasopharyngeal microbiota of healthy humans, maintaining a commensal relationship with the host. However, it can cause several diseases with high mortality and morbidity, such as meningitis, bacteremia and pneumonia, and other common respiratory tract infections such as otitis media and sinusitis. Colonization of the nasopharynx is a prerequisite for pneumococcal disease development and transmission of bacteria. Colonization rates vary according to geographical location and socioeconomic conditions, with prevailing rates of 20–90% in children less than five years of age, and 1–10% in adults [1–4]. Simultaneous colonization by multiple pneumococcal strains is also common and up to 50% of colonized children carry simultaneously two or more strains of S. pneumoniae [5–8].
The widespread use of PCVs led to the substitution of serotypes both in colonization and IPD. Since PspA is a variable protein, its use as vaccine antigen could lead to a phenomenon similar to serotype substitution. We have thus tested nasal immunization with rPspAs from different clades adjuvanted with wP in a model of co-colonization of mice with two strains expressing different PspAs. This model aims to mimic the common situation of simultaneous co-colonization with two or more strains in children. We have previously shown that nasal immunization with rPspA adjuvanted with wP induced protection against nasopharyngeal colonization in mice , but the model of co-colonization tested here should be a more stringent situation.