Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides

ArticleinVaccine 23(17-18):2298-303 · April 2005with2 Reads
DOI: 10.1016/j.vaccine.2005.01.041 · Source: PubMed
We have investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting group A streptococcal (GAS) vaccine delivery approach. LCP constructs were synthesised incorporating peptides from the M protein conserved carboxy terminal C-repeat region, the amino terminal type-specific region and from both of these regions. Immunisation with the constructs without adjuvant led to the induction of peptide-specific serum IgG antibody responses, heterologous opsonic antibodies, and complete protection from GAS infection. These data indicate that protective immunity to GAS infection can be evoked using the self-adjuvanting LCP system, and point to the potential application of this system in human mucosal GAS vaccine development.
    • "There was also a trial to use both C-terminal sequence and N terminal sequence in the same vaccine (Brandt et al., 2000). The sequence peptide known as J14m a 29 obtained from C-terminal sequence of M protein has promising in vivo results (Vohra et al., 2005; Batzloff et al., 2005; Olive et al., 2005).. Other model of vaccine described the use of combined epitopes from T and B memory cells that produce effective and specific immune response not retricted to specific HLA class II molecules cells (). There was similar approach that used C-terminal sequence resembling that of B cells epitopes constructed in Australia called P145(Pruksakorn et al., 1994; Brandt et al., 2000) and later on modified to be more safe with no cross reactivity(Hayman et al., 1997). "
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    • "This was followed by another 30-valent vaccine construction that was immunogenic in rabbits, inducing significant levels of bactericidal antibodies against the specific vaccine serotypes plus 24 different GAS strains. In addition, vaccines based on the highly conserved M protein C-terminal region have also been designed141516. Our vaccine model (StreptInCor) incorporates the 55-amino-acid sequence from the M5 protein C-terminal region and encompasses epitopes for both human B and T cells [21]. In conclusion, the data presented herein indicate that StreptInCor is able to induce a robust protective immune response in outbred mice. "
    [Show abstract] [Hide abstract] ABSTRACT: Infection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections.
    Full-text · Article · Apr 2013
    • "The covalent conjugation of lipids (self-adjuvanting moiety) to synthetic peptides has been demonstrated as a potentially safe method to adjuvant otherwise poorly immunogenic peptides.9101112 Over the past decade, our laboratory has performed extensive studies of subunit vaccine candidates against GAS.13141516 We have also developed a unique lipid core peptide (LCP) system [17] featuring a lipopeptide moiety (inbuilt adjuvant), a polylysine branching core [18] (carrier), and multiple peptides (antigen) in one molecular entity. "
    [Show abstract] [Hide abstract] ABSTRACT: Development of a synthetic vaccine against group A streptococcal infection is increasingly paramount due to the induction of autoimmunity by the main virulent factor - M protein. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with carriers and adjuvants. One of the promising approaches to deliver antigenic peptides is to assemble peptides on a suitable template which directs the attached peptides to forma well defined tertiary structure. For self-adjuvanting human vaccines, the conjugation of immunostimulatory lipids has been demonstrated as a potentially safe method. This study describes the design and optimized synthesis of two lipopeptide conjugated carbohydrate templates and the assembling of peptide antigens. These lipopeptide-carbohydrate assembled multivalent vaccine candidates were obtained in high yield and purity when native chemical ligation was applied. Circular dichroism studies indicated that the template-assembled peptides form four alpha-helix bundles. The developed technique extends the use of carbohydrate templates and lipopeptide conjugates for producing self-adjuvanting and topology-controlled vaccine candidates.
    Full-text · Article · Jan 2009
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