Update on the development of Group A Streptococcus vaccines

Ajay Castro, Sowmya; Dorfmueller, Helge C.

doi:10.1038/s41541-023-00730-x

Cited by 10 publications

(14 citation statements)

References 26 publications

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“…Outcomes for this phase 1 clinical trial indicated that intramuscular administration of StreptAnova adjuvanted with alum was well tolerated and no clinical evidence of autoimmune response and no laboratory evidence of tissue cross-reactive antibodies [ 133 , 134 ]. The immunogenicity of StreptAnova in healthy volunteers secreted IgG antibodies and induced strong opsonophagocytic killing activity in selected GAS strains [ 133 , 134 ]. Furthermore, approval for a phase 1a clinical trial of P*17/S2 combivax and J8/S2 combivax intramuscularly immunised into healthy volunteers was commenced, however, to date, no further information is available from this trial [ 132 ].…”

Section: Recent Advances Of Gas Vaccine Developmentmentioning

confidence: 99%

“…Protein-based subunits containing the N-terminal regions of M proteins from 30 GAS stereotypes. [133,134] The most advanced N-terminal peptide-based vaccine, StreptAnova was assessed in phase I clinical trials in 23 healthy volunteers in 2020 [133,134]. Outcomes for this phase 1 clinical trial indicated that intramuscular administration of StreptAnova adjuvanted with alum was well tolerated and no clinical evidence of autoimmune response and no laboratory evidence of tissue cross-reactive antibodies [133,134].…”

Section: Gas Vaccine Candidates In Clinical Trialsmentioning

confidence: 99%

“…[133,134] The most advanced N-terminal peptide-based vaccine, StreptAnova was assessed in phase I clinical trials in 23 healthy volunteers in 2020 [133,134]. Outcomes for this phase 1 clinical trial indicated that intramuscular administration of StreptAnova adjuvanted with alum was well tolerated and no clinical evidence of autoimmune response and no laboratory evidence of tissue cross-reactive antibodies [133,134]. The immunogenicity of StreptAnova in healthy volunteers secreted IgG antibodies and induced strong opsonophagocytic killing activity in selected GAS strains [133,134].…”

Section: Gas Vaccine Candidates In Clinical Trialsmentioning

confidence: 99%

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Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

Fan,

Toth,

Stephenson

2024

Vaccines

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Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described

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Section: Recent Advances Of Gas Vaccine Developmentmentioning

confidence: 99%

Section: Gas Vaccine Candidates In Clinical Trialsmentioning

confidence: 99%

Section: Gas Vaccine Candidates In Clinical Trialsmentioning

confidence: 99%

See 1 more Smart Citation

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

Fan,

Toth,

Stephenson

2024

Vaccines

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“…Moreover, repeated mild infections can lead to autoimmune sequelae such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD) [1,2]. Acknowledgment of the significant burden of disease caused by GAS infections has sparked renewed interest in the development of a vaccine that can safely prevent all the clinical manifestations caused by GAS [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Alum-Adjuvanted Peptide and Carbohydrate Conjugate Vaccine Candidates against Group A Streptococcus Pharyngeal Infection in a Non-Human Primate Model

Rivera-Hernandez,

Carnathan,

Richter

et al. 2024

Vaccines

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Vaccine development against group A Streptococcus (GAS) has gained traction in the last decade, fuelled by recognition of the significant worldwide burden of the disease. Several vaccine candidates are currently being evaluated in preclinical and early clinical studies. Here, we investigate two conjugate vaccine candidates that have shown promise in mouse models of infection. Two antigens, the J8 peptide from the conserved C-terminal end of the M protein, and the group A carbohydrate lacking N-acetylglucosamine side chain (ΔGAC) were each conjugated to arginine deiminase (ADI), an anchorless surface protein from GAS. Both conjugate vaccine candidates combined with alum adjuvant were tested in a non-human primate (NHP) model of pharyngeal infection. High antibody titres were detected against J8 and ADI antigens, while high background antibody titres in NHP sera hindered accurate quantification of ΔGAC-specific antibodies. The severity of pharyngitis and tonsillitis signs, as well as the level of GAS colonisation, showed no significant differences in NHPs immunised with either conjugate vaccine candidate compared to NHPs in the negative control group.

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“…Acute rheumatic fever (ARF) is an inflammatory reaction triggered by Group A Streptococcus infection which usually occurs approximately two to three weeks following a sore throat illness. 1,2 ARF is characterized by several clinical symptoms consisting of polyarthritis migrant (35-88%) and carditis (50-78%) which usually cause mitral or aortic valve regurgitation. Besides that, other signs that usually accompany ARF include abnormal involuntary movement or Sydenham chorea (2-19%), erythema marginatum (<6%), subcutaneous nodule (1-13%), and increased laboratory values such as erythrocyte sedimentation rate, neutrophils, and CRP.…”

Section: Introductionmentioning

confidence: 99%

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

Ambari,

Desandri,

Dwiputra

et al. 2024

F1000Res

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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.

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Update on the development of Group A Streptococcus vaccines

Cited by 10 publications

References 26 publications

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

Efficacy of Alum-Adjuvanted Peptide and Carbohydrate Conjugate Vaccine Candidates against Group A Streptococcus Pharyngeal Infection in a Non-Human Primate Model

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

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