HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation.

Abstract

We have analyzed by ex vivo ELISPOT the anti-vaccinia cytotoxic T lymphocyte responses of peripheral blood mononuclear cells from humans vaccinated with Dryvax vaccine. More than 6,000 peptides from 258 putative vaccinia ORFs predicted to bind the common molecules of the HLA A1, A2, A3, A24, B7, and B44 supertypes were screened with peripheral blood mononuclear cells of 31 vaccinees. A total of 48 epitopes derived from 35 different vaccinia antigens were identified, some of which (B8R, D1R, D5R, C10L, C19L, C7L, F12, and O1L) were recognized by multiple donors and contain multiple epitopes recognized in the context of different HLA types. The antigens recognized tend to be >100 residues in length and are expressed predominantly in the early phases of infection, although some late antigens were also recognized. Viral genome regulation and virulence factor were recognized most frequently, whereas few structural proteins were immunogenic. Finally, most epitopes were highly conserved among vaccinia virus Western Reserve, variola major and modified vaccinia Ankara, supporting their potential use in vaccine and diagnostic applications.

• Authors: Carla Oseroff, Ferdynand Kos, Huynh-Hoa Bui, Bjoern Peters, Valerie Pasquetto, Jean Glenn, Tara Palmore, John Sidney, David C Tscharke, Jack R Bennink, Scott Southwood, Howard M Grey, Jonathan W Yewdell, Alessandro Sette
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 102 Issue 39 Pg. 13980-5 (Sep 27 2005) ISSN: 0027-8424 [Print] United States
• PMID: 16172378 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Viral
• DryVax vaccine
• Epitopes, T-Lymphocyte
• HLA Antigens
• Histocompatibility Antigens Class I
• Peptides
• Smallpox Vaccine
• Viral Proteins

Topics

• Amino Acid Sequence
• Antigens, Viral (immunology)
• Epitopes, T-Lymphocyte (analysis)
• Gene Expression Regulation, Viral
• Genes, Viral (genetics)
• HLA Antigens (metabolism)
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Molecular Sequence Data
• Peptides (blood, genetics, metabolism)
• Smallpox (prevention & control)
• Smallpox Vaccine (immunology, therapeutic use)
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccination
• Vaccinia (immunology, virology)
• Vaccinia virus (genetics, immunology, pathogenicity)
• Viral Proteins (genetics, immunology, metabolism)
• Virulence (genetics)