Immunization With A Combination Of Three Pneumococcal Proteins Confers Additive And Broad Protection Against Streptococcus Pneumoniae Infections In Mice

Backgroud Heptavalent protein-polysaccharide conjugate vaccine (PCV7) and 23-valent pneumococcal polysaccharide vaccine (PPV23) are the two vaccines currently being used against S. pneumoniae, while with some major drawbacks as high cost, limited coverage and serotype replacement. Protein vaccine is potential to remove the barriers of cost and coverage, making an effective and broad coverage vaccine feasible.Methods Our study was carried out from the following standpoints: vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. A focal pneumococcal pneumoniae model, mimicking the natural pneumococcal infection, was used to evaluate pneumococci on lung colonization. Besides, we set up models of invasive diseases, which were used to evaluate their systemic protective effects against pneumococcal infections. System vaccination with the combination of three antigens was evaluated based on the protections against pneumococcal serotypes 14, 19F, 23F, 6B, 3, and 2. Still, a mixture of serotypes 14, 6B, 19F, 23F was used as challenge bacteria. PPV23 and PCV7 were served as positive control, and their protective effects were compared with that achieved by the combination in parallel.Results Lpl andΔA146 Ply proteins have been successfully prepared by molecular technology and protein purification methods. The two protein candidates and ClpP were capable to elicit anti-specific antibody in serum. Anti-ΔA146Ply polyclonal serum could block the hemolysis effect arised from pneumolysin. Lpl, ClpP,ΔA146Ply singly or in combinations were sufficient to reduce bacterial load at least 10-fold in lungs (P<0.05). The combination of the three antigens showed the best ablity in reducing bacterial load. Similar protection partern was abserved in intraperitoneal challenge infections, in which the combination conferred the best protection of 70% efficiency against 150×LD50 pneumococcal D39 infecions. Surpringly, in intranasal challenge models with D39, regimens containingΔA146 Ply elicited protection against infections. Taken together, intranasal challenge was suggested to be a more reasonable challenge routine should be used in evaluating the protective effects. The combination vaccine (IC247) conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and, 80% protection against pneumococcal strain 6B. Even so, immunity to IC247 could confer 70% protection against pneumococcal infection with a mixture of four serotypes. Our results showed IC247 was as effective as the currently used vaccines (PCV7 and PPV23). No protection was seen when antigen-specific antibodies were withdrawn from IC247 sera. Conclusions These results indicate that system immunization with IC247 could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models, in which the protection elicited was antibody mediated.