Next Generation Vaccines: Development of a Novel Streptococcus pneumoniae Multivalent Protein Vaccine

by Paola Cecchini, Claire Entwisle, Michael Joachim, Yin Pang, Kate A. Dalton, Sue Hill, Ann McIlgorm, Win-Yan Chan, Jeremy S. Brown, Camilo A. Colaco, Chris R. Bailey, and Sue W. Clarke
Volume 14, Issue 3 (Fall 2015)

Polysaccharide-based vaccines are widely used to protect against Streptococcus pneumoniae (S. pneumoniae) infections in infants and the elderly. However, their use is limited by strain specificity, which restricts both their geographical and economical utility. There is an urgent need for protein-based vaccines that are likely to provide broader, more economical protection against the global burden of pneumococcal disease. In this paper, we describe the pre-clinical development of a multi-subunit protein vaccine that can be manufactured efficiently and economically to meet this need. Genetically engineered Streptococcus pneumoniae TIGR4 B7.1 PlyD6 cell substrate was constructed to deliver non-toxic Ply. PnuBioVax™ S. pneumoniae vaccines were produced at ImmBio in a 1 L-scale fermenter as development batches. The process has been successfully “tech transferred” to a CMO for scale-up and production of toxicology and clinical supplies. Pre-clinical immunogenicity tests showed promising results for PnuBioVax. Rabbit sera generated by PnuBioVax were able to produce surface binding antibody and complement-mediated killing of S. pneumoniae for both TIGR4 and the heterologous strain 15B (not covered by pneumococcal conjugate vaccine [PCV]-13). No overall benefit to the immunogenicity by the addition of Alhydrogel was seen in the total IgG response. In passive protection studies in mice, serum raised against PnuBioVax in rabbits protected against challenge by S. pneumoniae TIGR4...

Cecchini P, Entwisle C, Joachim M, Pang Y, Dalton KA, Hill S, McIlgorm A, Chan W-Y, Brown JS, Colaco CA, Bailey CR, Clarke SW. Next generation vaccines: development of a novel Streptococcus pneumoniae multivalent protein vaccine. BioProcess J, 2015; 14(3): 18–33.

Posted online October 9, 2015.