Related Experiment Video
Updated: Feb 20, 2026
Experimental Human Pneumococcal Carriage
Published on: February 15, 2013
Physicochemical characterisation, immunogenicity and protective efficacy of a lead streptococcal vaccine: progress
Manisha Pandey1, Jessica Powell2, Ainslie Calcutt2
1Institute for Glycomics, Griffith University, Queensland, 4222, Australia. m.pandey@griffith.edu.au.
Abstract:
Globally, group A streptococcal infections are responsible for over 500,000 deaths per year. A safe vaccine that does not induce autoimmune pathology and that affords coverage for most GAS serotypes is highly desired. We have previously demonstrated that a vaccine based on the conserved M-protein epitope, J8 was safe and immunogenic in a pilot Phase I study. We subsequently improved vaccine efficacy by incorporation of a B-cell epitope from the IL-8 protease, SpyCEP, which protected IL-8 and enhanced neutrophil ingress to the site of infection. We have now substituted the carrier protein, diphtheria toxoid with its superior analogue, CRM197 which provides better immunogenicity and is widely used in licenced human vaccines. The new vaccine was compared with the DT conjugate vaccine to confirm that these modifications have not altered the physicochemical properties of the vaccine. This vaccine, when tested in an animal model of GAS infection, demonstrated significant reduction in systemic and local GAS burden, with comparable efficacy to the DT conjugate vaccine. The vaccine was shown to be equally effective in the presence of human plasma and in the presence of pre-existing DT-specific antibodies, thus minimising concerns regarding its potential efficacy in humans.
Insights
A new group A Streptococcus (GAS) vaccine shows promise, reducing bacterial burden in animal models. This improved vaccine, using CRM197, is safe and effective, even with pre-existing antibodies, offering hope against GAS infections.
Area of Science:
- Vaccinology
- Infectious Diseases
- Immunology
Background:
- Group A Streptococcus (GAS) infections cause over 500,000 deaths annually, necessitating a safe and broadly protective vaccine.
- Previous vaccine candidates showed safety and immunogenicity, but further improvements in efficacy are needed.
- Existing vaccine strategies require enhancement to cover multiple GAS serotypes and avoid autoimmune complications.
Purpose of the Study:
- To develop an improved, safe, and immunogenic vaccine against Group A Streptococcus (GAS).
- To evaluate the efficacy of a novel GAS vaccine candidate utilizing CRM197 as a carrier protein.
- To assess vaccine performance under conditions mimicking human physiological environments.
Main Methods:
- A new GAS vaccine was formulated using the conserved M-protein epitope (J8) and a SpyCEP B-cell epitope, conjugated to CRM197.
- Physicochemical properties were compared to a diphtheria toxoid (DT) conjugate vaccine.
- Vaccine efficacy was tested in a murine model of GAS infection, assessing bacterial burden.
- The vaccine's effectiveness was evaluated in the presence of human plasma and pre-existing DT-specific antibodies.
Main Results:
- The CRM197-conjugated vaccine demonstrated significant reduction in both systemic and local GAS burden in an animal model.
- Efficacy was comparable to the DT conjugate vaccine.
- The vaccine maintained effectiveness in the presence of human plasma and pre-existing anti-DT antibodies.
Conclusions:
- The novel GAS vaccine candidate, conjugated to CRM197, is safe, immunogenic, and effective in reducing GAS burden.
- The use of CRM197 offers improved immunogenicity and broad applicability in human vaccines.
- This vaccine shows potential for widespread human use, addressing concerns about efficacy in diverse populations.
Related Concept Videos
01:28Preclinical Development: Overview
01:51Vaccinations
01:11Clinical Trials: Overview