Journal of Vaccines & Vaccination

Development of Pneumococcal surface protein Antigen (PspA) based Pneumococcal vaccine showing enhanced protective immunity when conjugated to Vi capsular polysaccharide from Salmonella typhi

5^th 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.