Identification of SP1683 as a pneumococcal protein that is protective against nasopharyngeal colonization

Abstract

Serotype-independent protein-based pneumococcal vaccines represent attractive alternatives to capsular polysaccharide-based vaccines. The aim of this study was to identify novel immunogenic proteins from Streptococcus pneumoniae that may be used in protein-based pneumococcal vaccine. An immunoproteomics approach and a humanized severe combined immunodeficient mouse model were used to identify S. pneumoniae proteins that are immunogenic for the human immune system. Among the several proteins identified, SP1683 was selected, recombinantly produced, and infection and colonization murine models were used to evaluate the capacity of SP1683 to elicit protective responses, in comparison to known pneumococcal immunogenic proteins (PhtD and detoxified pneumolysin, dPly). Immunisation with SP1683 elicited a weaker antibody response than immunisation with PhtD and did not provide protection in the model of invasive disease. However, similar to PhtD, it was able to significantly reduce colonization in the mouse model of nasopharyngeal carriage. Treatment with anti-IL17A and anti-IL17F antibodies abolished the protection against colonization elicited by SP1683 or PhtD + dPly, which indicated that the protection afforded in this model was Th17-dependent. In conclusion, intranasal immunization with the pneumococcal protein SP1683 conferred IL17-dependent protection against nasopharyngeal carriage in mice, but systemic immunization did not protect against invasive disease. These results do not support the use of SP1683 as an isolated pneumococcal vaccine antigen. Nevertheless, SP1683 could be used as a first line of defence in formulations combining several proteins.

Screening for Th17-Dependent Pneumococcal Vaccine Antigens: Comparison of Murine and Human Cellular Immune Responses

“…Indeed, we found that the protective hit rate was highest in the pool of proteins that induced higher responses in all the screens. The 16 protective antigens that we identified have not been reported previously as conferring protection, with the single exception of SP1683, which was reported as a Th17-dependent antigen that protects against colonization while this article was being prepared (32). While the protection against colonization by any single antigen did not approach that of SPWCV in mouse models (Fig.…”

In-silico Analysis of Pneumococcal Heat-Shock Protein (DnaJ) to Predict Novel Multi-Epitope Vaccine Candidates

“…8 No. 2 been analyzed in clinical trials and their protective effects are still limited to a subset of pneumococcal strains [12,13]. The candidate protein should mostly be well-conserved among pneumococcal serotypes and be able to stimulate T-helper cells, resulting in a strong memory response [13].…”