Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides.
ABSTRACT 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.
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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.PLoS ONE 04/2013; 8(4):e60969. · 3.53 Impact Factor
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ABSTRACT: Currently there is no commercial Group A Streptococcus (GAS; S. pyogenes) vaccine available. The development of safe GAS vaccines is challenging, researchers are confronted with obstacles such as the occurrence of many unique serotypes (there are greater than 150 M types), antigenic variation within the same serotype, large variations in the geographical distribution of serotypes, and the production of antibodies cross-reactive with human tissue which can lead to host auto-immune disease. Cell wall anchored, cell membrane associated, secreted and anchorless proteins have all been targeted as GAS vaccine candidates. As GAS is an exclusively human pathogen, the quest for an efficacious vaccine is further complicated by the lack of an animal model which mimics human disease and can be consistently and reproducibly colonized by multiple GAS strains.Current topics in microbiology and immunology 12/2012; · 3.47 Impact Factor
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ABSTRACT: Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.Human vaccines & immunotherapeutics. 12/2013; 10(3).