Rheumatic Fever (RF) is a severe, non-contagious inflammatory illness. It develops as a complication of an untreated infection with the bacterium Streptococcus pyogenes, commonly known as Group A Strep (GAS). Currently, there is no widely approved or commercially available vaccine to prevent RF. Research is focused on developing a vaccine that targets the GAS bacterium to eliminate the threat of this debilitating disease.
The Link Between Strep Infection and Rheumatic Fever
Rheumatic Fever is not a direct infection but an autoimmune response. It is triggered when the body produces antibodies to fight an untreated Group A Strep (GAS) infection, such as strep throat. A phenomenon called molecular mimicry occurs, where the immune system confuses certain bacterial proteins with proteins found naturally in the body’s own tissues.
The primary target of this confusion is the M-protein, a surface protein on the GAS bacterium. The M-protein structure closely resembles proteins found in the heart, joints, and brain. Antibodies created to attack the M-protein then cross-react and launch an attack on these similar host tissues. This autoimmune attack leads to the inflammation and damage characteristic of Rheumatic Fever, often resulting in Rheumatic Heart Disease (RHD).
Progress Toward a Group A Strep Vaccine
Vaccine development focuses on targeting the M-protein of Group A Strep, which is the primary antigen that triggers the harmful immune response. The goal is to create a vaccine that prompts a protective immune response against the bacteria. Crucially, it must do this without initiating the cross-reactive autoimmune attack on the body’s own tissues. Several candidate vaccines are currently progressing through human clinical trials.
One advanced strategy involves multivalent M-protein vaccines, designed to protect against numerous circulating bacterial strains. These candidates aim to generate antibodies that eliminate GAS bacteria before the infection progresses to Rheumatic Fever. Early-stage clinical trials, such as Phase I and II, have shown promising results regarding safety and the ability to produce protective antibodies. However, a licensed product is not yet available.
Unique Challenges in Vaccine Design
The development of a universal Group A Strep vaccine is slowed by two hurdles: the extensive variability of the bacteria and the need for absolute safety. The M-protein is encoded by the emm gene, which has over 250 known genetic variations, called emm types. Since immunity is often specific to the emm type, a vaccine must contain enough different M-protein components to cover the majority of strains circulating globally.
The high level of strain variability means that a vaccine effective in one region may offer poor coverage in another part of the world. Initial attempts at a GAS vaccine were halted decades ago due to concerns that the M-protein components used might cause the cross-reactive immune response. Scientists must meticulously engineer the vaccine to use only non-autoimmune-triggering parts of the M-protein. This safety requirement remains the most difficult barrier to overcome before a vaccine can be approved for widespread use.
Current Methods for Disease Prevention
Since a vaccine is still under development, current strategies for preventing Rheumatic Fever rely on antibiotics. Primary prevention focuses on eradicating the initial Group A Strep infection. This involves diagnosing strep throat quickly and treating it with a full course of antibiotics, typically penicillin. This eliminates the bacteria before the autoimmune process begins, and its effectiveness in preventing a first episode of Rheumatic Fever is well-established.
Secondary prevention is reserved for patients who have already experienced an episode of Rheumatic Fever. These individuals are at high risk for recurrence, and each subsequent episode can lead to further, irreversible heart damage. This involves continuous antibiotic prophylaxis, often with monthly intramuscular injections of long-acting benzathine benzylpenicillin. This regimen is maintained for several years, or even decades, to prevent any future GAS infection.