title: Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein.
abstract: The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2(b)-restricted epitopes (S436-443 and S525-532) and one H-2(d)-restricted epitope (S366-374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection.
authors.affiliation: Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania Health System, and The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhi
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.forename: Heather
authors.initials: H
authors.lastname: Jordan
authors.forename: Katie
authors.initials: K
authors.lastname: Suchma
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Gregory
authors.initials: G
authors.lastname: Schumer
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.forename: Julie L
authors.initials: JL
authors.lastname: Boyer
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003062:Codon; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006183:H-2 Antigens / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007114:Immunization; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control; D064370:Spike Glycoprotein, Coronavirus; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D003062:Codon; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines