CD4 T cell antigens from Staphylococcus aureus Newman strain identified following immunization with heat-killed bacteria.
Staphylococcus aureus is a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-γ) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-γ-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens from S. aureus has made it difficult to design effective vaccines. The goal of this study was to identify S. aureus proteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from the S. aureus Newman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI.
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
Paulraj K
PK
Lawrence
Bachra
B
Rokbi
Nadège
N
Arnaud-Barbe
Eric L
EL
Sutten
Junzo
J
Norimine
Kevin K
KK
Lahmers
Wendy C
WC
Brown
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D006801:Humans; D007114:Immunization / Q000379:methods; D059386:Reverse Genetics / Q000379:methods; D013203:Staphylococcal Infections / Q000517:prevention & control* / Q000662:veterinary*; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D013209:Staphylococcal Vaccines