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Immune response against M protein-conserved region peptides from prevalent group A Streptococcus in a North Indian
Varun K Gupta1, Sasank Sekhar2, Vanita Dhanda1
1Department of Experimental Medicine and Biotechnology, Chandigarh, India.
Background:
Group A streptococci (GAS) cause infections with a high prevalence in most developing countries. A GAS vaccine under trial that is based on the amino-terminus of the M protein provides type-specific immunity, and hence seems ineffective in India because of heterogeneous emm types. However, the conserved C-terminal region of the M protein protects against multiple serotypes. In this paper, the immune response generated against the conserved C-repeat region of the M protein was checked in an Indian population to establish their vaccine candidature.
Methods:
When screened for GAS, patients with pharyngitis, rheumatic fever/rheumatic heart disease (RF/RHD), and invasive disease showed heterogeneous emm types, out of which five prevalent types (1-2, 11, 49, 75 and 112) were selected for the study. The C-terminal region of their M proteins showed conserved C1-, C2-, and C3-repeats. The C1-repeat was more diverse and had two different J14-like sequences. Peptides to these C-terminal regions (J14.1 and J14-R6) were designed. Antibodies against these peptides were analyzed using the sera of 130 GAS-infected volunteers.
Results:
Serum antibodies were significantly higher in patients with acute rheumatic fever, RHD, and invasive disease than in patients with pharyngitis or the healthy controls. The serum antibodies to these peptides was higher in teenagers and adults than in children.
Conclusion:
Results showed an association between streptococcal disease progression and the age-related development of immunity to the conserved regions. Hence, these peptides could be considered protective in impeding streptococcal infections worldwide.
Insights
Group A Streptococcus (GAS) vaccine development in India faces challenges due to diverse strains. This study explored immunity to conserved M protein regions, finding higher antibody levels in severe disease and older individuals, suggesting potential for broad-spectrum GAS vaccines.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Group A Streptococcus (GAS) infections are prevalent globally, particularly in developing nations.
- Current GAS vaccines targeting the M protein's amino-terminus offer type-specific immunity, limiting efficacy against India's diverse emm types.
- The conserved C-terminal region of the M protein presents a potential target for broad-spectrum GAS vaccines.
Purpose of the Study:
- To investigate the immune response to conserved C-repeat regions of the M protein in an Indian population.
- To evaluate the vaccine candidature of peptides derived from the M protein's C-terminal conserved regions.
Main Methods:
- Selected five prevalent GAS emm types in India (1-2, 11, 49, 75, 112) with conserved C-terminal C1, C2, and C3 repeats.
- Designed peptides (J14.1 and J14-R6) targeting conserved C-terminal regions, including diverse J14-like sequences.
- Analyzed serum antibodies against these peptides in 130 GAS-infected volunteers.
Main Results:
- Significantly higher serum antibodies to M protein peptides were observed in patients with acute rheumatic fever, rheumatic heart disease, and invasive GAS disease compared to pharyngitis patients and healthy controls.
- Antibody levels were higher in teenagers and adults than in children, indicating age-related immunity development.
Conclusions:
- An association exists between streptococcal disease progression and age-dependent immunity to conserved M protein regions.
- These conserved peptides show promise as protective agents against diverse streptococcal infections globally.
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