Identification and assessment of new vaccine candidates for group A streptococcal infections.
Group A Streptococcus (GAS) is a human-specific pathogen responsible for a wide variety of human diseases. Numerous GAS surface antigens interact with the human immune system and only some of these proteins have been studied in depth. A few of these may elicit protective response against GAS infection. In this study, we have used an in silico approach to identify antigenic peptides from GAS surface proteins. Putative GAS surface proteins from the M1 GAS genome were identified by the presence on LPxTG cell-wall anchoring motif and an export signal sequence. This technique identified 17 proteins of known or putative function, and another 11 which do not have known homologues. Peptides derived from predicted antigenic sequences near the amino terminus of six of these proteins, and another seven peptides derived from the two known surface proteins, GRAB and MtsA, were conjugated to keyhole lymphocyanin (KLH), and investigated for their capacity to induce opsonic antibody responses in outbred Quackenbush mice. All peptide-KLH antisera demonstrated opsonic capacity against both 88/30 and M1 GAS. However, KLH sera alone was also able to induce opsonic antibodies, suggesting that anti-KLH antibodies contributed to the opsonisation seen in the peptide-KLH antisera. KLH is therefore a promising carrier molecule for potential GAS peptide vaccines.
McMillan
David J
DJ
Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, Brisbane, Australia.davidm@qimr.edu.au
Batzloff
Michael R
MR
Browning
Cindy L
CL
Davies
Mark R
MR
Good
Michael F
MF
Sriprakash
Kadaba S
KS
Janulczyk
Robert
R
Rasmussen
Magnus
M
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D003198:Computer Simulation; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics / Q000276:immunology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence; D016366:Open Reading Frames / Q000235:genetics / Q000276:immunology; D009895:Opsonin Proteins / Q000494:pharmacology; D010455:Peptides / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D017931:DNA Primers; D004269:DNA, Bacterial; D000939:Epitopes; D009895:Opsonin Proteins; D010455:Peptides; D022541:Streptococcal Vaccines