Contribution of the complement system to protection elicited by pneumococcal vaccines including PhTD, PspA, PspC and pneumolysin

Abstract

Streptococcus pneumoniae is responsible for a high number of deaths worldwide, affecting mostly young children and the elderly, particularly in developing countries. The currently available vaccines, composed of polysaccharydes alone or conjugated to protein carriers have high production costs and confer limited coverage. Therefore, many pneumococcal proteins have been evaluated as potential vaccine candidates with promising results. However, in order to maximize the vaccine coverage, it is necesary to include multiple antigens in the formulation. Due to the pivotal role of the complement system in immunity against pneumococcus, the present work will determine the protective potential of proteins that inhibit complement deposition on the bacterial surface, combined or fused in chimeras. This strategy would eliminate the compensatory effects of these antigens, rendering a higher protective efficacy to the vaccine. The selected proteins were PhTD and its N- and C-terminal fragments, the N-terminal region of PspA family 1, PlD1 and PspC. The immune response induced by the vaccines will be investigated, and protection will be assessed in mouse models of colonization and sepsis. The interaction between PhTD and factor H will be evaluated by ELISA and confirmed by FACS. C3b deposition on pneumococcal surface and bacterial phagocytosis in vitro will also be analysed. (AU)