Group A Streptococcus vaccine Development: An Indian public health imperative.

Background: Group A Streptococcus (GAS) is a significant pathogen responsible for a wide range of diseases, including severe complications such as Rheumatic Heart Disease (RHD), which predominantly affect low- and middle-income countries (LMICs) like India. GAS infections impact over 800 million individuals annually, resulting in approximately 639,000 deaths due to RHD complications. Despite significant advancements, developing an effective GAS vaccine has faced several challenges, including the complexity of GAS virulence mechanisms, the diversity of emm types, and the lack of suitable preclinical models. Recent vaccine research has focused on both M protein-based and non-M protein-based vaccines, with several candidates showing promising results. However, current vaccines only address 50 % of the prevalent emm types in India, highlighting the need for further research and development.

Objective: This review aims to examine the historical and current progress in GAS vaccine development, identify key challenges, and explore future strategies, with a focus on the Indian public health context.

Content: A comprehensive review of existing literature on GAS and its complications was conducted, focusing on the global and Indian burden of GAS infections, the resurgence of scarlet fever, and the emergence of virulent strains such as M1UK. The study also reviewed recent global initiatives like the Cairo Accord and the 71st World Health Assembly's resolution on RHD to emphasize the need for international collaboration in vaccine development. Continued global cooperation, intensified research efforts, and targeted public health initiatives are essential for overcoming the challenges in GAS vaccine development. Advocacy and investment in this area are crucial for reducing the global burden of GAS infections and their associated complications. This study aims to provide comprehensive genomic data on GAS isolates from India, enabling comparisons with global findings, highlighting regional differences, and contributing to a more comprehensive understanding of GAS epidemiology and pathogenicity.