Evaluation of synthetic, M type-specific peptides as antigens in a multivalent group A streptococcal vaccine

Bruner, Mark W.; James, Allison; Beall, Bernard; Carlone, George M.; Ades, Edwin W.; Johnson, Scott E.; Guarner, Jeannette; Sampson, J S

doi:10.1016/s0264-410x(03)00165-8

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…As N-terminus epitopes are highly variable and geographically specific, vaccines that use them effectively are likely to employ a multivalent approach, with a variety of N-terminal antigens (from the most prevalent M types in the region or targeted population) combined by chemical synthesis or the recombinant approach [55,66]. Recombinant DNA technology is used to build multivalent recombinant genes that express multiple protective M protein-derived peptides (fusion proteins).…”

Section: Major Antigen Targets For Gas Vaccinesmentioning

confidence: 99%

Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

et al. 2019

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Group A Streptococcus (GAS) infection can cause a variety of diseases in humans, ranging from common sore throats and skin infections, to more invasive diseases and life-threatening post-infectious diseases, such as rheumatic fever and rheumatic heart disease. Although research has been ongoing since 1923, vaccines against GAS are still not available to the public. Traditional approaches taken to develop vaccines for GAS failed due to poor efficacy and safety. Fortunately, headway has been made and modern subunit vaccines that administer minimal bacterial components provide an opportunity to finally overcome previous hurdles in GAS vaccine development. This review details the major antigens and strategies used for GAS vaccine development. The combination of antigen selection, peptide epitope modification and delivery systems have resulted in the discovery of promising peptide vaccines against GAS; these are currently in preclinical and clinical studies.

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Section: Major Antigen Targets For Gas Vaccinesmentioning

confidence: 99%

Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

et al. 2019

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“…The development of a vaccine to prevent GAS infection would offer an ideal means to prevent RHD (responsible for the greatest health burden) and other GAS-associated diseases. Numerous research groups – are therefore working toward the development of prophylactic GAS vaccines, with the most advanced research focusing on the GAS cell-surface M-protein.…”

Section: Introductionmentioning

confidence: 99%

Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

et al. 2007

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The development of 16 self-adjuvanting group A streptococcal vaccine candidates, composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG antibodies were detected following subcutaneous immunization of BALB/c (H-2 (d)) mice with each construct without the need for an additional adjuvant. The effect of changing the order of P25, J14, and lipid moiety attachment or incorporation of P25 and J14 into a lipid-core peptide system on antibody titers was assessed. The point of lipid moiety attachment had the greatest influence on systemic J14-specific IgG antibody titers. Overall, the best vaccines featured a C-terminal lipid moiety, conjugated through a lysine residue to P25 at the N-terminus, and J14 on the lysine side chain.

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“…The specificity of the antibodies was controlled by their lack of reactivity with the OVA-linked ELDKWA-containing protein (NEQELLELDKWASLWNC) 6 -OVA. Reciprocally, the antibodies from mice immunized with PADRE-ELDKWA reacted with OVA-linked ELDKWA and not with the OVA-linked p145 [(LRRDLDASREAKKQVEKALEC) 6 -OVA] (data not shown).…”

Section: Resultsmentioning

confidence: 95%

“…The M protein is a surface molecule that plays a major role in the pathogenicity of GAS by blocking the deposition of C3b onto the bacterial surface [5]. Its N‐terminal sequence is highly antigenic, but despite promising results against the major M types [6, 7], this variability may overwhelm the power of candidate polyvalent vaccines. A high number of M types have been described by the serological method of Lancefield [8] and thereafter by studying the corresponding genes [9] that encode more than 124 different emm types [10].…”

Section: Introductionmentioning

confidence: 99%

Induction of a Mucosal Immune Response to the Streptococcal M Protein by Intramuscular Administration of a PADRE‐ASREAK Peptide

et al. 2004

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In a previous study, it was shown that an intramuscular administration of amino acid PADRE-ELDKWA sequence induced a mucosal immune response to a conserved epitope of human immunodeficiency virus in mice. In the same model, here it is shown that this method can be used with a selected peptide from the M protein of group A streptococci. The PADRE-ASREAK sequence was injected in mice by the intramuscular route. Antibodies against M protein were detected in extracts of mucosal tissues and in serum. The repertoire isotypes of serum immunoglobulin G (IgG) and mucosal IgA and IgG antibodies varied, according to the dose of injected peptide. The highest mucosal IgA antibody response was obtained with 0.01 mg of antigen per injection, whereas the systemic IgG antibody response increased with 10 mg of antigen. Mucosal antibody production against streptococci was confirmed by immunofluorescence analysis. These results provide evidence that this novel approach of mucosal vaccination may be of advantage for bacterial systems and suggest a new field of investigation based on synthetic peptide analogues.

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Evaluation of synthetic, M type-specific peptides as antigens in a multivalent group A streptococcal vaccine

Cited by 6 publications

References 21 publications

Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

Induction of a Mucosal Immune Response to the Streptococcal M Protein by Intramuscular Administration of a PADRE‐ASREAK Peptide

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