# Unveiling the Group A Streptococcus Vaccine-Based L-Rhamnose from Backbone of Group A Carbohydrate: Current Insight Against Acute Rheumatic Fever to Reduce the Global Burden of Rheumatic Heart Disease

## TL;DR

This paper discusses a new vaccine approach using L-Rhamnose from Group A Streptococcus to prevent rheumatic heart disease by avoiding harmful cross-reactive antibodies.

## Contribution

The novel use of L-Rhamnose from Group A Carbohydrate as a safe and effective vaccine component against Group A Streptococcus.

## Key findings

- L-Rhamnose-based vaccines increase IgG antibody titers without causing cross-reactive antibodies in animal tissues.
- The vaccine shows strong immunogenicity and safety in pre-clinical studies.
- L-Rhamnose is absent in human tissues, reducing the risk of autoimmune reactions.

## Abstract

Group A Streptococcus (GAS) is a widely distributed bacterium that is Gram-positive and serves as the primary cause of acute rheumatic fever (ARF) episodes. Rheumatic heart disease (RHD) is a sequela resulting from repeated ARF attacks which are also caused by repeated GAS infections. ARF/RHD morbidity and mortality rates are incredibly high in low- and middle-income countries. This is closely related to poor levels of sanitation which causes the enhanced incidence of GAS infections. Management of carditis in RHD cases is quite challenging, particularly in developing countries, considering that medical treatment is only palliative, while definitive treatment often requires more invasive procedures with the high costs. Preventive action through vaccination against GAS infection is one of the most effective steps as a solution in reducing RHD morbidity and mortality due to curative treatments are expensive. Various developments of M-protein-based GAS vaccines have been carried out over the last few decades and have recently begun to enter the clinical stage. Nevertheless, this vaccination generates cross-reactive antibodies that might trigger ARF assaults as a result of the resemblance between the M-protein structure and proteins found in many human tissues. Consequently, the development of a vaccine utilizing
L-Rhamnose derived from the poly-rhamnose backbone of Group A Carbohydrate (GAC) commenced. The
L-Rhamnose-based vaccine was chosen due to the absence of the Rhamnose biosynthesis pathway in mammalian cells including humans thus this molecule is not found in any body tissue. Recent pre-clinical studies reveal that
L-Rhamnose-based vaccines provide a protective effect by increasing IgG antibody titers without causing cross-reactive antibodies in test animal tissue. These findings demonstrate that the
L-Rhamnose-based vaccine possesses strong immunogenicity, which effectively protects against GAS infection while maintaining a significantly higher degree of safety.