Abstract
Knowledge-based vaccinology can reveal uncharacterized antigen candidates for a new generation of protein-based anti-pneumococcal vaccines. DiiA, encoded by the sp_1992 locus, is a surface protein containing either one or two repeats of a 37mer N-terminal motif that exhibits low interstrain variability. DiiA belongs to the core proteome, contains several conserved B-cell epitopes, and is associated with colonization and pathogenesis. Immunization with DiiA protein via the intraperitoneal route induced a strong IgG response, including different IgG subtypes. Vaccination with DiiA increased bacterial clearance and induced protection against sepsis, conferring 70% increased survival at 48 h post-infection when compared to the adjuvant control. The immunogenic response and survival rates in mice immunized with a truncated DiiA version lacking 119 N-terminal residues were remarkably lower, confirming the relevance of the repeat zone in the immunoprotection by DiiA. Intranasal immunization of mice with the entire recombinant protein elicited mucosal IgG and IgA responses that reduced bacterial colonization of the nasopharynx, confirming that this protein might be a vaccine candidate for reducing the carrier rate. DiiA constitutes an example of how functionally unannotated proteins may still represent promising candidates that can be used in prophylactic strategies against the pneumococcal carrier state and invasive disease.
Highlights
Streptococcus pneumoniae is one of the most prevalent etiological agents of both invasive and noninvasive disease including pneumonia, meningitis and sepsis
We demonstrate that dimorphic invasion-involved protein A (DiiA) is able to induce an immunoprotective response reducing the carrier state and protecting against pneumococcal sepsis, suggesting that this protein can be deemed a promising antigenic vaccine candidate
Among the principal pneumococcal surface proteins detected by ANTIGENome, SP_0107 and SP_1992 (DiiA) are the only ones that do not show any known InterPro domain in the section exposed to the medium
Summary
Streptococcus pneumoniae is one of the most prevalent etiological agents of both invasive and noninvasive disease including pneumonia, meningitis and sepsis This relevant microorganism remains one of the most deadly and costly pathogens with a rate over one million deaths per year worldwide affecting mainly children under five years old and elderly adults [1,2]. The current vaccine formulations are based on selected capsular types that may be conjugated to a carrier protein in order to elicit protection against the pediatric and adult population [3]. Serotype replacement linked to the long-term pressure exerted by vaccination has led to emerging infective genotypes that have previously incorporated alternative capsules, which eventually tend to dominate the
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