Technology

Gamma-PNTM: a serotype independent pneumococcal vaccine.

 

“GPN Vaccines is a private biotechnology company developing a vaccine against Streptococcus pneumoniae (the pneumococcus) – the world’s foremost bacterial pathogen. S. pneumoniae is responsible for causing life-threatening pneumonia, bacteraemia and meningitis, as well as otitis media (middle ear infections). Each year it causes 1-2 million deaths worldwide, killing more children than AIDS, malaria and tuberculosis combined. There are now 98 different serotypes of S. pneumoniae and the best vaccine currently on the market only protects against 13 of them. Gamma-PNTM – GPN Vaccines’ new S. pneumoniae vaccine is being developed to protect children and adults against all S. pneumoniae strains, regardless of strain serotype.”

About Gamma-PNTM

GPN Vaccines’ technology is a proprietary engineered strain of S. pneumoniae that lacks capsular polysaccharide, is avirulent and is safe to handle; and when cultured and inactivated with high-energy photons (“gamma-rays”), a whole cell gamma-irradiated pneumococcal vaccine is produced, which we call “Gamma-PNTM”.  This whole cell vaccine (WCV) is capable of inducing broad-spectrum T- and B-cell immunity to cross-reactive protein antigens of the pneumococcus that when tested in experimental animals, is sufficient to provide protection against different pathogenic pneumococcal strains irrespective of strain serotype.

A scanning electron micrograph of Gamma-PNTM shows that the gamma-irradiation process used to inactivate (and kill) the vaccine strain has no effect on bacterial morphology.

HOW IT WORKS

Streptococcus pneumoniae is the world’s foremost bacterial pathogen. It is considered part of the “normal flora” of the human nasopharynx. Humans are the only known host and anywhere from 5 to 95% of the population (depending on age and socio-economic factors) may be asymptomatically colonized by the organism at any one time. Such “carriers” are the principal reservoir for transmission of the bacterium in the community. Nasopharyngeal carriage is a dynamic process and the numbers of pneumococci are usually kept under control by the innate and acquired immune defences of the host.

 

However, if this delicate balance is disturbed, the pneumococcus can invade deeper tissues, resulting in a spectrum of diseases including pneumonia, bacteraemia, meningitis, otitis media and sinusitis.

 

In developing countries, up to 1 million children under 5 years of age die each year from pneumonia, of which S. pneumoniae is the single most common cause.  Indeed, pneumonia is responsible for 20-25% of all deaths in this age group in those countries. In developed countries such as Australia, death rates from pneumococcal pneumonia are highest in persons >65 years, while in young children, pneumococcal otitis media is highly prevalent, with massive impact on health care costs.

In the US, an estimated 900,000 individuals get pneumococcal pneumonia each year, and as many as 400,000 are hospitalised.  About 5-7% of people who need care in hospital due to pneumococcal pneumonia die from it.

 

Gamma-PNTM is a non-encapsulated (and hence avirulent) derivative of S. pneumoniae. The absence of capsular polysaccharide maximises exposure of conserved surface protein antigens to the immune system, such that immunisation of experimental animals with Gamma-PNTM elicits significant protection against lethal sepsis when animals are challenged with different S. pneumoniae serotypes.

 

This protection has been found to be dependent B cells that produce antibodies and on IL-17-producing T cells. The use of gamma-rays (photons) to inactivate S. pneumoniae appears to give Gamma-PNTM an advantage over other inactivated S. pneumoniae vaccines, presumably because the structures of conserved surface protein antigens are maintained during vaccine production leading to effective induction of protective immunity.

Publications

2019

David SC, Laan Z, Minhas V, Chen AY, Davies J, Hirst TR, McColl SR, Alsharif M, Paton JC. (2019) Enhanced safety and immunogenicity of a psaA mutant whole-cell inactivated pneumococcal vaccine. Immunol. Cell Biol. doi.org/10.1111/imcb.12257

 

2018

GPN Vaccines Factsheet © February 2018 “Gamma-PNTM: A Serotype-Independent (Universal) Pneumococcal Vaccine. [download]

 

2017

David SC, Lau J, Singleton EV, Babb R, Davies J, Hirst TR, McColl SR, Paton JC, Alsharif M. (2017) The effect of gamma-irradiation conditions on the immunogenicity of whole inactivated influenza A virus. Vaccine 35: 1071-1079. [download]

 

2016

Babb R, Chen A, Ogunniyi AD, Hirst TR, Kara EE, McColl SR, Alsharif M, Paton JC. (2016)  Enhanced protective responses to a serotype-independent pneumococcal vaccine when combined with an inactivated influenza vaccine.  Clinical Science 131: 169-180. [download]

 

Babb R, Chen A, Hirst TR, Kara EE, McColl SR, Ogunniyi AD, Paton JC, Alsharif M. (2016)  Intranasal vaccination with γ–irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses. Clinical Science 130: 697-710. [download]

Protecting children and adults from the world’s foremost bacterial pathogen