Preventing Group A Strep Infections and GAS Vaccine Research

Table of Contents

1. Handwashing and Respiratory Hygiene
2. Shared Utensils and Personal Items
3. Respiratory Isolation in Healthcare Settings
4. Secondary Prophylaxis with Benzathine Penicillin G
5. Vaccine Development Challenges
6. Multi-Valent M Protein Vaccine Candidates
7. Non-M Protein Vaccine Targets
8. Where GAS Vaccine Trials Stand Today
9. Key Research Papers
10. Connections
11. Featured Videos

Handwashing and Respiratory Hygiene

The U.S. Centers for Disease Control and Prevention (CDC) names close contact with a person who has strep throat as the most common risk factor for illness, and notes that the bacteria often spread to other people in the same household (CDC: About Strep Throat). Its clinical guidance states that good hand hygiene and respiratory etiquette can reduce the spread of group A strep bacteria (CDC: Clinical Guidance for Strep Throat).

The CDC’s handwashing guidance describes scrubbing with soap for at least 20 seconds — about as long as humming “Happy Birthday” twice — including the backs of the hands, between the fingers and under the nails. When soap and water are not available, it describes hand sanitizer that contains at least 60% alcohol, and it states that soap and water is the best way to get rid of germs (CDC: Clean Hands).

Key times for handwashing listed by the CDC include (CDC: Clean Hands):

• Before, during and after preparing food
• Before and after eating
• After using the toilet
• After coughing, sneezing or blowing the nose
• Before and after treating wounds

The CDC’s strep throat prevention steps also include covering coughs and sneezes and keeping wounds clean and bandaged (CDC: About Strep Throat).

Transmission inside the home has been studied less than might be expected. A 2024 systematic review found 28 texts published between 2000 and March 2023; only 7 gave enough detail to identify how GAS passed between household members (direct contact in 4, objects such as bedding, clothing, other fabric and medical equipment in 2, and contact with animals in 1), most described outbreaks of invasive infection, and the authors concluded that the literature on household transmission is limited (PubMed PMID: 38478731).

Back to Table of Contents

Shared Utensils and Personal Items

Among the CDC’s prevention steps for strep throat are not sharing cups, utensils and bites of food with people who are sick, and washing cups, utensils and plates after a sick person has used them (CDC: About Strep Throat).

A 2006 systematic review of how long hospital pathogens persist on dry inanimate surfaces reported that most gram-positive bacteria, Streptococcus pyogenes among them, survive for months on dry surfaces (PubMed PMID: 16914034).

Toothbrushes have been studied as a possible reservoir. In a 1998 study of 104 children with GAS pharyngotonsillitis, GAS was isolated after 10 days of oral penicillin V from 11 (11%) of the toothbrushes and from 18 (17%) of the children; the toothbrushes of 5 of those 18 children (28%) were colonized, and GAS was also found on 4 of 21 removable orthodontic appliances. In laboratory tests, GAS persisted on unrinsed toothbrushes for up to 15 days but was not isolated from rinsed toothbrushes beyond day 3. The authors concluded that toothbrushes and appliances harbouring GAS may contribute to persistence of GAS in the throat and may account for some penicillin treatment failures (PubMed PMID: 9738808).

On how long a treated person remains infectious, the CDC’s clinical guidance states that treatment with an appropriate antibiotic for 12 hours or longer limits a person’s ability to transmit group A strep, and that people with GAS pharyngitis stay home from work, school or daycare until they are afebrile and at least 12–24 hours after starting appropriate antibiotic therapy (CDC: Clinical Guidance for Strep Throat).

Back to Table of Contents

Respiratory Isolation in Healthcare Settings

Hospitals layer transmission-based precautions on top of standard precautions according to the type of GAS infection. The CDC’s isolation precautions guideline (Appendix A) lists the following for group A streptococcal disease (CDC: Isolation Precautions, Appendix A):

• Major skin, wound or burn infection: contact plus droplet plus standard precautions, until 24 hours after effective therapy begins, and until drainage stops or can be contained by a dressing
• Minor or limited skin, wound or burn infection: standard precautions, if a dressing covers and contains the drainage
• Endometritis (puerperal sepsis): standard precautions
• Pharyngitis or scarlet fever in infants and young children: droplet plus standard precautions, until 24 hours after effective therapy begins
• Pneumonia: droplet plus standard precautions, until 24 hours after effective therapy begins
• Serious invasive disease: droplet plus standard precautions, until 24 hours after effective therapy begins

For serious invasive disease, the same table notes that outbreaks have been documented, that contact precautions apply to draining wounds, and that antimicrobial prophylaxis is recommended in select cases (CDC: Isolation Precautions, Appendix A). Invasive GAS infections such as necrotizing fasciitis and streptococcal toxic shock syndrome are therefore placed under droplet precautions for the first 24 hours of effective treatment, not exempted from them.

Back to Table of Contents

Secondary Prophylaxis with Benzathine Penicillin G

Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by GAS. Rheumatic heart disease (RHD) is a chronic disease caused by accumulated heart valve damage from a single severe or, more commonly, multiple recurrent episodes of ARF (PubMed PMID: 27188830).

A 2009 American Heart Association scientific statement describes a person who has had an attack of rheumatic fever as being at very high risk of recurrences after later GAS pharyngitis, and states that such a person needs continuous antimicrobial prophylaxis to prevent recurrences. It names penicillin as the agent of choice for secondary prophylaxis, with sulfadiazine or a macrolide or azalide as acceptable alternatives in penicillin-allergic individuals (PubMed PMID: 19246689).

A 2016 review describes secondary penicillin prophylaxis as proven in randomized trials to prevent recurrence of ARF and as the single most important step in managing ARF, and states that intramuscular benzathine penicillin G (BPG) is superior to oral penicillin. It reports that mid-twentieth-century studies found 40–60% of patients with ARF progressed to RHD (PubMed PMID: 27188830).

On the injection interval, the same review reports that patients given penicillin every fourth week, compared with every third week, were more likely to have undetectable serum penicillin levels between doses and were fivefold more likely to have prophylaxis failure. Contemporary data from New Zealand, however, showed ARF recurrences were rare among people fully adherent to a 4-weekly BPG regimen: 0.07 cases per 100 patient-years, against 1.4 cases per 100 patient-years for prophylaxis failure overall, including people who were less than fully adherent (PubMed PMID: 27188830).

The review lists the factors that set the duration of secondary prophylaxis (PubMed PMID: 27188830):

• Time since the last episode: ARF recurrences are more common in the first 5 years after the last episode
• Age: recurrence is less common after age 25 and uncommon after age 30
• Heart involvement: whether carditis was present at presentation, and how severe RHD is at follow-up
• Environment: particularly the likelihood of ongoing exposure to GAS, such as young children in the household

On that basis, the review reports that the recommended duration is usually a minimum of 10 years after the most recent episode of ARF or until age 18–21 years, whichever is longer, and that recent guidelines recommend continuing until age 30–35 for moderate RHD and until age 40 for severe RHD (PubMed PMID: 27188830).

The GOAL Trial: Prophylaxis for Latent RHD

Echocardiographic screening can find RHD at an early, latent stage. The GOAL trial, published in 2022, randomly assigned Ugandan children and adolescents aged 5 to 17 with latent RHD to injections of benzathine penicillin G every 4 weeks for 2 years or to no prophylaxis. Of 102,200 young people screened, 926 had a confirmed diagnosis and were eligible, 916 were randomized and 818 were included in the analysis. Echocardiographic progression at 2 years occurred in 3 participants (0.8%) in the prophylaxis group and 33 (8.2%) in the control group (risk difference −7.5 percentage points; 95% CI −10.2 to −4.7). Two participants in the prophylaxis group had serious adverse events attributed to prophylaxis, including one mild anaphylactic reaction (under 0.1% of all doses given). The authors concluded that prophylaxis reduced the risk of progression at 2 years, and that further research is needed before population-level screening can be recommended (PubMed PMID: 34767321).

Access and Adherence

The 2016 review reports that just over half of eligible patients were receiving secondary antibiotic prophylaxis in recent data, that the barriers mainly reflect a lack of systems to identify and track patients with RHD in the community, and that ARF and RHD registers have been advocated as a step towards control (PubMed PMID: 27188830). In October 2024 the WHO published a guideline on the prevention and diagnosis of rheumatic fever and RHD that covers the treatment of suspected GAS pharyngitis and skin infections, long-term antibiotic prophylaxis, interventions to increase adherence to it, and screening for early RHD (WHO: guideline on rheumatic fever and RHD, 2024).

Back to Table of Contents

Vaccine Development Challenges

The 2005 global estimate counted at least 15.6 million prevalent cases of RHD with 233,000 deaths a year, at least 663,000 new cases and 163,000 deaths a year from invasive GAS disease, more than 111 million prevalent cases of GAS skin infection (pyoderma) and over 616 million new cases of GAS pharyngitis a year; the authors noted that data from developing countries are poor (PubMed PMID: 16253886). The Global Burden of Disease 2015 analysis estimated 319,400 deaths from RHD and 33.4 million cases of RHD in 2015, with the highest age-standardized mortality and prevalence in Oceania, South Asia and central sub-Saharan Africa (PubMed PMID: 28834488). GAS is also an important driver of antibiotic use: the 2019 WHO paper cites US ambulatory-care surveys in which 60% of consultations for sore throat led to an antibiotic prescription, although most pharyngitis is viral (PubMed PMID: 30624673).

The same 2019 paper lists the impediments to GAS vaccine development to date: a lack of relevant animal models, high genetic diversity of antigen targets, safety concerns, and a lack of consensus on clinical endpoints for proof of concept, with uncertain or insufficient market incentives as a further obstacle to private-sector involvement (PubMed PMID: 30624673).

Obstacle 1: The M Protein Diversity Problem

The M protein on the bacterial surface is both a virulence factor and a vaccine antigen, and it is the basis of the emm typing used in epidemiology. A 2014 paper reported that more than 220 variants of the protein had been described, and proposed grouping them into 48 emm clusters of closely related M proteins that share binding and structural properties (PubMed PMID: 24799598).

The distribution of emm types differs by region. The 2019 WHO paper describes emm1 and emm12 as the two most common types in Asia, Latin America and the wealthiest countries, which have the lowest strain diversity; these types are less prevalent in Africa and the Pacific, where strain diversity is greater. It states that M protein sequences chosen according to the strains prevalent in high-income countries might give poor coverage in high-burden regions (PubMed PMID: 30624673).

Obstacle 2: Molecular Mimicry and Autoimmune Risk

A 2003 review describes molecular mimicry in rheumatic carditis as a sequence of steps: cross-reactive autoantibodies form against the GAS carbohydrate antigen N-acetyl-glucosamine and cardiac myosin; these antibodies react with the valve endothelium, which becomes inflamed and expresses VCAM-1; T cells that respond to streptococcal M protein sequences then infiltrate the valve (PubMed PMID: 12700052).

The history of the safety concern is set out in the 2023 vaccine landscape review. Tens of thousands of people, including children, received M protein vaccines before the 1960s, and human challenge studies of purified M protein in the 1970s showed protection against GAS pharyngitis of up to 89%, with no serious adverse events detected in vaccinees. In 1979 the US Food and Drug Administration issued a regulation (21 CFR 610.19) that barred “Group A streptococcus organisms or their derivatives” from vaccines, citing an uncontrolled study in which a partially purified type 3 M protein vaccine was given to 21 healthy siblings of patients with rheumatic fever; two vaccinees developed rheumatic fever and one possible rheumatic fever. The FDA revoked the regulation in 2006 (PubMed PMID: 36788225; original 1969 case report: PubMed PMID: 5818242).

The 2019 WHO paper states that the validity of the concern raised by that single study was later questioned: all three children had documented GAS infection before the onset of ARF, all were siblings of ARF patients, and they had received very high, repeated doses of a crude M protein preparation. It adds that trials have often monitored for autoimmunity with serum autoantibody panels, tissue cross-reactive antibody assays and echocardiography, and that there is a strong perception that autoantibody panels and echocardiographic monitoring are poor screening tools of limited value (PubMed PMID: 30624673).

Back to Table of Contents

Multi-Valent M Protein Vaccine Candidates

Multivalent recombinant M protein vaccines are built from N-terminal M peptides that contain opsonic epitopes but do not contain epitopes that cross-react with human tissue (PubMed PMID: 31843270). Other M protein-based candidates use peptides from the more conserved C-terminal region instead (PubMed PMID: 36788225).

The 26-Valent and 30-Valent Vaccine Programs

Between 2006 and 2016, early-phase trials in healthy adult volunteers tested four candidates: 6-valent, 26-valent and 30-valent N-terminal M protein vaccines, and a conserved C-repeat region M protein vaccine. The 2023 landscape review reports that no serious safety signals were detected and that immunogenicity data were encouraging for all four (PubMed PMID: 36788225).

The 30-valent candidate, developed by Dale and colleagues at the University of Tennessee, combines four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminium hydroxide. In its observer-blinded Phase I trial, healthy adults were randomized 2:1 to the vaccine or an alum comparator at 0, 30 and 180 days; 23 vaccinated participants and 13 controls completed the study. The vaccine was well tolerated, with no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies, and it produced significant increases in antibody levels to 24 of the 30 component M antigens; opsonophagocytic killing was seen against selected M types in participants who seroconverted to those peptides (PubMed PMID: 31843270).

The 2019 WHO paper states that the peptides were selected from the acute and invasive isolates most prevalent in North America and Europe, and that although cross-opsonic antibodies against non-vaccine serotypes have been shown in the laboratory, their clinical significance remains to be determined (PubMed PMID: 30624673). The 2023 review gives the candidate’s theoretical coverage, based on a genomic analysis of 2,083 GAS genomes, as 48% globally, ranging from 28% in East Africa to 75% in North America; its developers have proposed that coverage could reach 80.3% of isolates in Africa when cross-opsonic antibodies and emm-cluster typing are taken into account. A Phase 2 efficacy study was planned, pending funding (PubMed PMID: 36788225).

Conserved-Region M Protein Candidates

A group at Griffith University in Australia has developed vaccines based on conserved peptides from the M protein C-terminus. An early version, J8 conjugated to diphtheria toxoid (J8-DT) and adsorbed onto aluminium hydroxide, was tested in a randomized, double-blind Phase I trial in 10 healthy adults (8 vaccine, 2 placebo) given a single 50 μg dose. No serious adverse events were reported over 12 months; 2 of 13 adverse events were judged vaccine-related, both mild. The vaccine raised vaccine-specific antibodies, which peaked 28 days after immunization and declined during follow-up (PubMed PMID: 29965967).

The current versions combine a C-terminal M protein peptide (J8 or P*17) with K4S2, a peptide from the SpyCEP protease, each conjugated to the CRM197 carrier protein. The 2023 review reports that the J8 allele is found in only 37% of GAS genomes, but that the candidates are expected to give about 98% coverage because J8 alleles cross-react immunologically, and that in mice both protected against skin and systemic infection with hypervirulent strains (PubMed PMID: 36788225). The protocol for their Phase I trial in Edmonton, Canada, published in 2024, plans to enrol 30 healthy volunteers aged 18–45 with no pre-existing valvular heart disease, with doses at 0, 3 and 6 weeks and a rabies vaccine as comparator; safety is the primary outcome (PubMed PMID: 39563457).

A further C-terminal candidate from the University of São Paulo, a 55-amino-acid peptide from conserved regions of the M5 protein, was preclinical at the time of the 2023 review; its epitopes were found in 23% of GAS strains in the genomic analysis, while an earlier study by its developers reported 71% conservation of the sequence among M proteins (PubMed PMID: 36788225).

Back to Table of Contents

Non-M Protein Vaccine Targets

The 2023 landscape review states that, given the potential but unproven safety concerns of M protein-based vaccines, several candidates are designed around other antigens that give broad coverage across strains and have lower potential to cross-react with host tissue. It reports that these protein antigens are found in 95–99% of characterized GAS isolates worldwide (PubMed PMID: 36788225).

Conserved Antigens Under Study

The review describes these antigens (PubMed PMID: 36788225):

• Group A Carbohydrate (GAC): a surface polysaccharide with a poly-rhamnose backbone and an N-acetylglucosamine (GlcNAc) side chain, highly conserved and expressed in all GAS isolates
• Streptolysin O (SLO): a secreted pore-forming toxin, upregulated in virulent isolates
• SpyCEP (S. pyogenes cell envelope proteinase): a protease that drives immune evasion by cleaving interleukin-8
• SpyAD: a surface-exposed adhesin that mediates the bacterium’s interaction with host cells
• C5a peptidase (SCPA): an enzyme on the cell envelope that mediates resistance to phagocytosis by cleaving the chemotaxin C5a
• Trigger factor (TF): an enzyme essential for the secretion and maturation of the GAS cysteine protease
• Arginine deiminase (ADI): an enzyme that contributes to colonization and modulation of the host immune response
• T-antigens: variable proteins that together form a structurally conserved backbone of the GAS pilus, involved in adhesion, colonization and immune evasion

Combination Candidates

A 2020 review reports that combination vaccines containing multiple shared, cross-protective antigens have been efficacious in mouse and nonhuman primate models, and that adjuvants more potent than alum have enhanced protective immunogenicity (PubMed PMID: 32304470). The 2023 review lists four non-M candidates on a product development track, all preclinical at the time, each with a theoretical coverage above 95% (PubMed PMID: 36788225):

• A four-component candidate: native GAC conjugated to CRM197, with SLO, SpyCEP and SpyAD, adjuvanted with alum, which protected in mouse models; a Phase I dose-escalation study was being planned
• A candidate built on a modified GAC with the GlcNAc side chain removed (the side chain has been implicated in autoimmune cross-reactivity in RHD), conjugated to SpyAD and combined with SLO and SCPA; it protected mice against systemic and skin infection, with no observed cross-reactivity to human heart or brain tissue epitopes
• A five-protein candidate (SLO, SpyCEP, SCPA, TF and ADI): with alum it reduced the severity of pharyngitis and tonsillitis in nonhuman primates but did not protect against colonization, and in mice it protected against superficial skin infection but not invasive disease; with a squalene-based adjuvant it protected mice against invasive challenge, in the absence of opsonizing antibodies
• A T-antigen candidate from the University of Auckland made of three fusion proteins covering 18 T-antigens; in rabbits the antibodies also cross-reacted with the 3 sub-types not included, which would be expected to give more than 95% strain coverage

Back to Table of Contents

Where GAS Vaccine Trials Stand Today

A 2018 World Health Assembly resolution on rheumatic heart disease highlighted the interest in GAS vaccines to complement control strategies (PubMed PMID: 30624673). The WHO then published a Group A Streptococcus Vaccine Development Technology Roadmap in January 2019 (WHO: GAS vaccine development technology roadmap), together with preferred product characteristics for GAS vaccines (PubMed PMID: 30624673). The Strep A Vaccine Global Consortium (SAVAC), established in 2019, works to put the roadmap into action (PubMed PMID: 36788225).

The 2023 landscape review, written by SAVAC-linked authors, counts eight candidates on a product development track — four M protein-based and four built on non-M antigens. All had shown proof of concept in preclinical models; one (the 30-valent candidate) had shown safety and immunogenicity in a completed Phase I trial, and at least four others were poised to enter clinical trials (PubMed PMID: 36788225). No candidate described in that review had entered an efficacy trial.

The review identifies the gaps holding the field back: correlates of protection are unknown, animal models are not validated or standardized, and no candidates have been compared head to head. It also lists the scarcity of epidemiological and economic data from low- and middle-income countries, the need for standardized safety surveillance, and the need for advocacy about the burden of GAS disease. SAVAC has highlighted the favourable cost-effectiveness and return on investment of a GAS vaccine (PubMed PMID: 36788225).

What the WHO Preferred Product Characteristics Describe

The 2019 paper presenting the WHO preferred product characteristics describes them as aspirational goals rather than minimum acceptable criteria. The abbreviated characteristics it gives include (PubMed PMID: 30624673):

• Indication: prevention of GAS pharyngitis, superficial skin infections, cellulitis, toxin-mediated disease, invasive infections and the antibiotic use they cause, as well as rheumatic fever, RHD and post-streptococcal glomerulonephritis
• Target population: a primary schedule for infants and/or young children
• Efficacy targets: 80% protection against non-severe, non-invasive confirmed GAS disease; 70% against confirmed cellulitis and other invasive infections; 50% against long-term immune-mediated sequelae
• Strain coverage: a preference for preventing at least 90% of the disease-causing isolates in the region where the vaccine is used
• Safety: a safety and reactogenicity profile at least as favourable as current WHO-recommended routine vaccines

The paper describes demonstrating efficacy against pharyngitis and skin infections in children as a key near-term strategic goal, because an RHD endpoint is distant and hard to measure, and because these infections lie on the causal pathway to many of the severe outcomes (PubMed PMID: 30624673).

Back to Table of Contents

Key Research Papers

1. Carapetis JR, Steer AC, Mulholland EK, Weber M (2005). The global burden of group A streptococcal diseases. Lancet Infectious Diseases, 5(11):685–694. — Estimates at least 517,000 deaths a year from severe GAS diseases, at least 18.1 million prevalent cases of severe GAS disease, and over 616 million new cases of GAS pharyngitis a year. — PubMed PMID: 16253886
2. Watkins DA et al. (2017). Global, Regional, and National Burden of Rheumatic Heart Disease, 1990–2015. New England Journal of Medicine, 377(8):713–722. — Global Burden of Disease 2015 analysis: 319,400 RHD deaths and 33.4 million RHD cases in 2015, with the highest age-standardized mortality and prevalence in Oceania, South Asia and central sub-Saharan Africa. — PubMed PMID: 28834488
3. Ralph AP, Carapetis JR (2013). Group A streptococcal diseases and their global burden. Current Topics in Microbiology and Immunology, 368:1–27. — Review of GAS transmission, prevention strategies, historical and geographical trends, and global burden. — PubMed PMID: 23242849
4. Dale JB, Walker MJ (2020). Update on group A streptococcal vaccine development. Current Opinion in Infectious Diseases, 33(3):244–250. — Review of vaccine antigens, combination vaccines, adjuvants and the obstacles to clinical development. [Editorial note: this entry previously cited a 2019 Microbiology Spectrum review by Dale et al. that could not be found on PubMed.] — PubMed PMID: 32304470
5. ESCMID Sore Throat Guideline Group; Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, Verheij T (2012). Guideline for the management of acute sore throat. Clinical Microbiology and Infection, 18 Suppl 1:1–28. — European guideline on diagnosing and treating acute sore throat. [Editorial note: this entry previously paired these authors with the title of a vitamin C and pneumonia meta-analysis and an unrelated journal; the vitamin C and pneumonia review on PubMed is by Hemilä (Cochrane, 2013) and concerns pneumonia, not GAS prevention.] — PubMed PMID: 22432746
6. Shulman ST et al. (2012). Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 55(10):e86–e102. — The IDSA guideline on diagnosis and treatment of GAS pharyngitis. — PubMed PMID: 22965026
7. Cunningham MW (2003). Autoimmunity and molecular mimicry in the pathogenesis of post-streptococcal heart disease. Frontiers in Bioscience, 8:s533–s543. — Describes the cross-reactive antibody and T-cell steps by which GAS infection leads to rheumatic carditis. — PubMed PMID: 12700052
8. Vekemans J, Gouvea-Reis F, Kim JH, et al. (2019). The Path to Group A Streptococcus Vaccines: World Health Organization Research and Development Technology Roadmap and Preferred Product Characteristics. Clinical Infectious Diseases, 69(5):877–883. — WHO preferred product characteristics, impediments to development, emm-type diversity, and rising invasive GAS in high-income countries. [Editorial note: this entry previously cited a 2019 Microbiology paper by Barnett et al., “Streptococcus pyogenes: no longer a commensal”, that could not be found on PubMed.] — PubMed PMID: 30624673
9. Walkinshaw DR, Wright MEE, Mullin AE, Excler JL, Kim JH, Steer AC (2023). The Streptococcus pyogenes vaccine landscape. npj Vaccines, 8(1):16. — Eight candidates on a product development track (four M protein-based, four non-M), their antigens, theoretical coverage and development status. [Editorial note: this entry previously cited a 2020 Current Topics in Microbiology and Immunology chapter by Dieye et al. that could not be found on PubMed.] — PubMed PMID: 36788225
10. Linnér A, Darenberg J, Sjölin J, Henriques-Normark B, Norrby-Teglund A (2014). Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome: a comparative observational study. Clinical Infectious Diseases, 59(6):851–857. — Swedish surveillance study of 67 patients with streptococcal toxic shock syndrome, 23 of whom received IVIG. — PubMed PMID: 24928291
11. Pastural É, McNeil SA, MacKinnon-Cameron D, et al. (2020). Safety and immunogenicity of a 30-valent M protein-based group A streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study. Vaccine, 38(6):1384–1392. — 23 vaccinated participants and 13 controls; well tolerated, no tissue cross-reactive antibodies, antibody increases to 24 of 30 M antigens. [Editorial note: this entry previously cited a 2021 Vaccine Phase I trial of a SpyCEP-based vaccine by McMillan et al. that could not be found on PubMed.] — PubMed PMID: 31843270
12. Sekuloski S, Batzloff MR, Griffin P, et al. (2018). Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial. PLoS One, 13(7):e0198658. — Phase I trial of a J8 peptide conjugate in 10 healthy adults. — PubMed PMID: 29965967
13. Meier-Stephenson V, Hawkes MT, et al. (2024). A phase 1 randomized controlled trial of a peptide-based group A streptococcal vaccine in healthy volunteers. Trials, 25(1):781. — Protocol for a Phase I trial of two conjugated M protein and SpyCEP peptide vaccines. — PubMed PMID: 39563457
14. Sanderson-Smith M, De Oliveira DM, Guglielmini J, et al. (2014). A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. Journal of Infectious Diseases, 210(8):1325–1338. — More than 220 M protein variants grouped into 48 emm clusters. — PubMed PMID: 24799598
15. Massell BF, Honikman LH, Amezcua J (1969). Rheumatic fever following streptococcal vaccination. Report of three cases. JAMA, 207(6):1115–1119. — The case report behind the 1979 FDA regulation on GAS vaccine antigens. — PubMed PMID: 5818242
16. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, Taubert KA (2009). Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation, 119(11):1541–1551. — Primary and secondary prevention of rheumatic fever. — PubMed PMID: 19246689
17. Carapetis JR, Beaton A, Cunningham MW, et al. (2016). Acute rheumatic fever and rheumatic heart disease. Nature Reviews Disease Primers, 2:15084. — Review covering pathogenesis, secondary prophylaxis, its duration and adherence. — PubMed PMID: 27188830
18. Beaton A, Okello E, Rwebembera J, et al. (2022). Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease. New England Journal of Medicine, 386(3):230–240. — The GOAL trial: progression at 2 years in 0.8% with prophylaxis vs 8.2% without. — PubMed PMID: 34767321
19. Brook I, Gober AE (1998). Persistence of group A beta-hemolytic streptococci in toothbrushes and removable orthodontic appliances following treatment of pharyngotonsillitis. Archives of Otolaryngology–Head & Neck Surgery, 124(9):993–995. — PubMed PMID: 9738808
20. Kramer A, Schwebke I, Kampf G (2006). How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infectious Diseases, 6:130. — PubMed PMID: 16914034
21. Enkel SL, Barnes S, Daw J, et al. (2024). Systematic Review of Household Transmission of Strep A: A Potential Site for Prevention That Has Eluded Attention. Journal of Infectious Diseases, 230(4):e798–e806. — PubMed PMID: 38478731

PubMed Topic Searches

1. Search PubMed: Streptococcus pyogenes vaccine and prevention

Back to Table of Contents

Connections

• All Bacteria
• Streptococcus Pyogenes Overview
• GAS Treatment & Prevention Hub
• Rheumatic Fever Complications
• Penicillin and Antibiotic Treatment
• Rheumatology Diseases
• Symptoms & Diagnosis
• Strep Throat
• Invasive Disease
• Diagnosis Tests

Featured Videos