There is currently no widely approved, commercially available vaccine to prevent strep throat, which is caused by the bacterium Group A Streptococcus (GAS). While this common infection is often easily treated, a preventive measure has remained elusive despite decades of research. The global health community recognizes the immense need for a vaccine to manage the burden of this ubiquitous pathogen. Researchers are making steady progress by focusing on the unique biology of the bacteria to overcome the complex obstacles that have prevented a successful vaccine.
Current Status of Strep Prevention
The current standard of care for strep throat remains a course of antibiotics, typically penicillin or amoxicillin, which are highly effective at clearing the infection. This treatment rapidly reduces symptoms and prevents the development of severe complications that can arise after the initial infection. These severe conditions are not caused by the bacteria itself but are the result of the body’s own immune response to the infection.
One of the most serious post-infection sequelae is Acute Rheumatic Fever (ARF), an inflammatory condition that can affect the joints, skin, and brain, and frequently causes permanent damage to the heart valves, leading to Rheumatic Heart Disease (RHD). Post-Streptococcal Glomerulonephritis (PSGN), a kidney disorder, can develop following a strep infection of the throat or skin. A vaccine is urgently needed because, globally, GAS infections cause over 500,000 deaths annually, primarily due to RHD.
The Scientific Hurdle
Developing a vaccine for Streptococcus pyogenes is challenging due to the structural complexity of the bacteria, particularly its primary virulence factor, the M protein. This protein extends from the bacterial surface and is the target for the body’s protective immune response. The M protein is highly variable, existing in over 200 distinct types, or serotypes, based on the differing structure of its N-terminal region.
A vaccine must induce immunity against the vast majority of circulating strains to be broadly effective, requiring a multivalent approach that incorporates many different M protein fragments. Past vaccine attempts were complicated by the risk of inducing an autoimmune reaction. Certain parts of the M protein share structural similarities with proteins found in human heart and kidney tissues; antibodies generated against the bacteria could mistakenly attack the body’s own cells and trigger conditions like ARF. Researchers must carefully select protein fragments to ensure they induce protection without causing this dangerous cross-reactivity.
Promising Vaccine Candidates in Development
Current research focuses on two main strategies to overcome these biological hurdles: multivalent M-protein vaccines and non-M-protein vaccines. The multivalent approach involves combining multiple M protein fragments from the most common serotypes into a single vaccine formulation. One candidate, StreptAnova, is a 30-valent vaccine that targets 30 specific M-protein serotypes and has demonstrated safety and immunogenicity in early-stage human clinical trials.
Other candidates are focusing on highly conserved regions of the M protein or on entirely different bacterial components. The StrepInCor vaccine, for instance, uses a conserved peptide from the C-terminal region of the M protein, which is found across many GAS strains. Researchers are investigating non-M-protein targets, such as the Group A Carbohydrate or specific enzymes, which remain consistent across all serotypes. These candidates are progressing through Phase I and Phase II clinical trials, confirming their safety and ability to generate an immune response in humans.