Abstract
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.
Highlights
Streptococcus pneumoniae is part of the nasopharyngeal microbiota of healthy humans, maintaining a commensal relationship with the host
Mice immunized with rPspA1+whole-cell pertussis vaccine (wP) showed a statistically significant increase in anti-rPspA1, anti-rPspA2 and antirPspA4 IgG titers, whereas animals immunized with rPspA4+wP showed a statistically significant increase in anti-rPspA3 and anti-rPspA4 IgG antibodies
Serum IgG antibodies raised against rPspA1+wP were able to bind to the surface of intact bacteria expressing PspA1 or PspA2, whereas antibodies raised against rPspA4+wP were able to bind to the surface of intact bacteria expressing PspA3 or
Summary
Streptococcus pneumoniae is part of the nasopharyngeal microbiota of healthy humans, maintaining a commensal relationship with the host. Though a net reduction in pneumococcal disease was observed in most countries, the widespread use of PCVs led to the substitution of prevalent serotypes, with an increase in incidence of non-vaccine serotype strains both in colonization [2,9] and IPD [10,11,12,13]. This phenomenon of serotype replacement is an example of the effect of the selective pressure promoted by vaccines that do not have complete coverage against all variants of the pathogen
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