Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae

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.

Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

“…These results also show that protection elicited by the protein formulation involves both PspA-specific responses and responses due to wP. A reduction of pneumococcal colonization induced by nasal immunization with wP has already been observed by our group [18,23]. Nasal wash samples from mice inoculated only with wP showed higher IL-6 levels before challenge and an early increase in CXCL-1 one day after challenge with pneumococci [18], which probably contributed to the reduction in the bacterial load in the nasopharynx, possibly by the early recruitment of phagocytic cells.…”

“…wP used in this work is composed of whole-cell pertussis inactivated with 0.2% formalin and was produced by Instituto Butantan (São Paulo, Brazil). Our group has previously used wP as an efficient nasal adjuvant for immunization with PspA [18,23]. Vaccines were administered in a volume of 10 µL using a micropipette.…”

“…We have shown that nasal immunization with recombinant PspA from clade 1 (PspA1) and PspA from clade 4 (PspA4) using the whole-cell pertussis vaccine (wP) as an adjuvant reduced colonization when challenge experiments were performed with a mixture of two isolates from serotype 6B expressing PspA1 and PspA4 or with a mixture of isolates of serotypes 6B (PspA clade 3 -PspA3) and 23F (PspA clade 2 -PspA2). The formulation did not lead to a pronounced increase in colonization of one isolate over the other, showing that the vaccine strategy would not favor replacement [18]. We now aim at testing the formulation against co-colonization models using VT and NVT isolates expressing different PspAs and compare nasal immunization with the protein formulation with parenteral vaccination with PCV.…”

Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A

“…https://doi.org/10.1371/journal.pone.0228055.g003 Our group has been working on the use of the adjuvant properties of wP for the formulation of PspA-based vaccines. Such combined formulations (wP plus recombinant purified PspA) have proved to be effective when inoculated through the nasal and through the subcutaneous routes in mice [8,9].…”

“…We have previously shown that the whole cell pertussis vaccine (wP) is a potent adjuvant to PspA, able to enhance the induction of specific antibodies and protection against invasive pneumococcal infection and nasal colonization in animal models [8,9]. Besides the whole bacteria, Pertussis toxin (PT) and Filamentous hemagglutinin (FHA) can also exert adjuvant activity when combined to PspA [10] leading us to propose that combined pertussis-PspA vaccines could be interesting approaches to immunize against infections caused by both Bordetella pertussis and pneumococci.…”