About Streptococcus pneumoniae
Streptococcus pneumoniae is a major pathogen found largely in the respiratory tract. Humans are the only known host and anywhere from 5 to 95% of the population may be asymptomatically colonized at any one time. Such carriers are the principal reservoir for transmission of the bacterium in the community. Nasopharyngeal carriage is a dynamic process, with the number of bacteria usually kept under control by the innate and acquired immune defences of the host. If this delicate balance is disturbed, however, the bacteria can invade deeper tissues and result in a spectrum of diseases including pneumonia, bacteraemia, meningitis, otitis media and sinusitis.
Streptococcus pneumoniae exists as 100 different serotypes distinguishable by the capsular polysaccharides expressed on the bacterial surface. Each serotype is immunologically different, such that most of the vaccines under development need to be targeted to each specific serotype. While polysaccharide conjugate vaccines (PCVs) have been highly effective against the serotypes that they cover, serotypes not covered by these vaccines often increase in prevalence (a phenomenon called serotype replacement), thereby offsetting reductions in disease burden and resulting in these vaccines becoming less effective over time.
While Streptococcus pneumoniae is sensitive to penicillin, resistance to penicillin and many other antibiotics has increased such that there is now a high rate of resistance. This leaves vaccination as a critical tool in disease control.
The Science
Our technology is based on a proprietary engineered strain of Streptococcus pneumoniae that lacks capsular polysaccharide, is avirulent and safe to handle. The strain is inactivated with gamma irradiation, creating a whole-cell pneumococcal vaccine called Gamma-PNTM. The gamma irradiation process provides an advantage over other inactivation methods because it maintains the structures of conserved surface protein antigens leading to effective induction of protective immunity. Unlike the surface carbohydrates which are serotype-specific, the surface proteins of S. pneumoniae are conserved allowing Gamma-PN to induce broad-spectrum T- and B-cell immunity to cross-reactive protein antigens of the bacteria. This is sufficient to provide protection against different pathogenic pneumococcal strains irrespective of strain serotype in various animal models. Indeed, rabbits immunised with Gamma-PN produce functional antibodies able to kill S. pneumoniae, namely a vigorous opsonophagocytic antibody (OPA) response, which outperforms currently approved vaccines.
Development Progress
We have developed a reproducible and scaled-up manufacturing process to GMP standard using state-of-the-art microbial fermentation and irradiation facilities in Australia. Our manufacturing process is vastly simpler and more cost-effective compared to the manufacture of polysaccharide conjugate vaccines, which require hundreds of process steps and over two years to complete a single batch. A GLP toxicology study commenced in Q2 2022 and we are planning a randomised, placebo-controlled, double-blind, sequential ascending-dose study to evaluate the acute safety, tolerability, and immunogenicity of Gamma-PN™ in comparison to Prevnar 13® and Pneumovax 23® in healthy adults aged 50-64 years of age. This clinical study will be conducted in Australia commencing in 2023.
