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

Cooperative Research Centre for Vaccine Technology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Division of Infectious Diseases and Immunology, Herston, Brisbane, Qld 4029, Australia.
Vaccine (Impact Factor: 3.62). 04/2005; 23(17-18):2298-303. 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.

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    • "In addition, vaccines based on the highly conserved M protein C-terminal region have also been designed [14]–[16]. 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]. "
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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. DOI:10.1371/journal.pone.0060969 · 3.23 Impact Factor
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    • "Previous reports have suggested other surface proteins of S. pyogenes as potential candidates for vaccines [38,39], but strain variation is generally a complication. For example, though the M protein is universally expressed by S. pyogenes, antibody against one strain may not be protective against other strains due to varying susceptibility to opsonophagocytosis [40] resulting from differences in M protein structure. "
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    ABSTRACT: The gram-positive bacterium Streptococcus pyogenes is a common pathogen of humans that causes invasive infections, toxic-shock syndrome, rheumatic fever, necrotizing fasciitis and other diseases. Detection of antibiotic resistance in clinical isolates has renewed interest in development of new vaccine approaches for control S. pyogenes sepsis. In the study presented, a novel protein vaccine was examined. The vaccine was based on a recombinant protein fusion between streptococcal pyrogenic exotoxin B (SpeB), a cysteinyl protease expressed by all clinical isolates, and streptococcal pyrogenic exotoxin A (SpeA), a superantigen produced by a large subset of isolates. A novel protein was produced by mutating the catalytic site of SpeB and the receptor binding surface of SpeA in a fusion of the two polypeptides. Vaccination of HLA-DQ8 transgenic mice with the SpeA-SpeB fusion protein protected against a challenge with the wild-type SpeA that was lethal to naïve controls, and vaccinated mice were protected from an otherwise lethal S. pyogenes infection. These results suggest that the genetically attenuated SpeA-SpeB fusion protein may be useful for controlling S. pyogenes infections. Vaccination with the SpeA-SpeB fusion protein described in this study may potentially result in protective immunity against multiple isolates of S. pyogenes due to the extensive antibody cross-reactivity previously observed among all sequence variants of SpeB and the high frequency of SpeA-producing strains.
    Journal of Immune Based Therapies and Vaccines 02/2008; 6(1):8. DOI:10.1186/1476-8518-6-8
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    • "Recently, Sandin et al. [22] and McArthur et al. [23] have commented on the capacity of fibrinogen and albumin to bind to the B- and C-repeats, respectively, causing inhibition of antibody binding under physiological conditions. Nevertheless, several studies [18,21,24-26] demonstrated the binding of anti-C-repeat antibody to GAS isolates, which are in agreement with our study. "
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    ABSTRACT: Most group A streptococcal (GAS) vaccine strategies have focused on the surface M protein, a major virulence factor of GAS. The amino-terminus of the M protein elicits antibodies, that are both opsonic and protective, but which are type specific. J14, a chimeric peptide that contains 14 amino acids from the M protein conserved C-region at the carboxy-terminus, offers the possibility of a vaccine which will elicit protective opsonic antibodies against multiple different GAS strains. In this study, we searched for J14 and J14-like sequences and the number of their repeats in the C-region of the M protein from GAS strains isolated from the Northern Thai population. Then, we examined the bactericidal activity of J14, J14.1, J14-R1 and J14-R2 antisera against multiple Thai GAS strains. The emm genes of GAS isolates were sequenced and grouped as 14 different J14-types. The most diversity of J14-types was found in the C1-repeat. The J14.1 type was the major sequence in the C2 and C3-repeats. We have shown that antisera raised against the M protein conserved C-repeat region peptides, J14, J14.1, J14-R1 and J14-R2, commonly found in GAS isolates from the Northern Thai population, are able to kill GAS of multiple different emm types derived from an endemic area. The mean percent of bactericidal activities for all J14 and J14-like peptide antisera against GAS isolates were more than 70%. The mean percent of bactericidal activity was highest for J14 antisera followed by J14-R2, J14.1 and J14-R1 antisera. Our study demonstrated that antisera raised against the M protein conserved C-repeat region are able to kill multiple different strains of GAS isolated from the Northern Thai population. Therefore, the four conserved "J14" peptides have the potential to be used as GAS vaccine candidates to prevent streptococcal infections in an endemic area.
    BMC Microbiology 02/2006; 6(1):71. DOI:10.1186/1471-2180-6-71 · 2.73 Impact Factor
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