Development of Pneumococcal surface protein Antigen (PspA) based Pneumococcal vaccine showing enhanced protective immunity when conjugated to Vi capsular polysaccharide from Salmonella typhi
5th Asia Pacific Global Summit and Expo on Vaccines & Vaccination
July 27-29, 2015 Brisbane, Australia

Neha Kothri

Posters-Accepted Abstracts: J Vaccines Vaccin

Abstract:

Background and Aim: Data from Phase I clinical trials showed that protein based pneumococcal vaccines induced poor immune responses. To address this problem the protein needs to be presented in a way that will induce a stronger antibody response that is more likely to protect humans. Our aim was to develop a more immunogenic vaccine by conjugating ?-helical region of PspA family 1 and 2, a protein common to all Streptococcus pneumoniae to Vi capsular polysaccharide from Salmonella typhi. The candidate vaccine provides better protection against lethal intravenous challenge with broad range of S.pneumoniae strains. Method: A high yielding, scalable method for fermentation and purification of Vi polysaccharide and of PspA family 1 and family 2 proteins have been optimized. Conjugation processes developed have more than 60-80% recoveries of both PspA and Vi polysaccharide and amongst a series of conjugates the most immunogenic conjugate was selected for protection studies against a range of S. pneumoniae strains. We tested the feasibility of formulating a bivalent vaccine containing Vi-PspA conjugates with PspA from both families 1 and 2 and tested its ability to induce cross-protection against strains with different PspAs. Spleen cell culture of immunized mice was checked for induction of both Th1/Th2 cytokines. Results: A series of Vi-PspA conjugates are prepared and tested in mice. Both Anti-Vi and Anti-PspA family 1&family 2 responses are significantly boosted upon conjugation (P<0.05). A high level of protection of vaccinated mice was observed when challenged with a pneumococcal strain expressing a clade that was present in the vaccine (monovalent or bivalent vaccine). Induction of a combination of Th1/Th2 cytokines was observed upon conjugation of protein with Vi polysaccharide. Conclusion: The bivalent conjugate vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide has the potential to protect against typhoid fever and infection caused by a broad range of S. pneumoniae stains. The vaccine has the added advantage that an adjuvant is not required to mount a robust protective response. It is anticipated that this vaccine can be produced at low cost and thus be made available to the world?s poorest communities at an affordable price.