Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion

Addie Embry, Xiangzhi Meng, Angelene Cantwell, Peter H. Dube, Yan Xiang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Vaccinia virus (VACV) is the vaccine for smallpox and a widely used vaccine vector for infectious diseases and cancers. The majority of the antibodies elicited by live VACV vaccination respond to virion structural proteins, including many integral membrane proteins on the intracellular mature virion (MV). Here, we showed that antibody response to an exogenous antigen delivered by VACV was greatly enhanced by incorporating the antigen as an integral membrane protein of MV. We constructed recombinant VACV expressing a Yersinia pestis protective antigen, LcrV, unmodified or fused with either a signal peptide or with the transmembrane domain of VACV D8 protein (LcrV-TM). Electron microscopy showed that LcrV-TM was displayed on the surface of MV. Importantly, VACV expressing LcrV-TM elicited a significantly higher titer of anti-LcrV antibody in mice than viruses expressing other forms of LcrV. Only mice immunized with LcrV-TM-expressing VACV were protected from lethal Y. pestis and VACV WR challenges. Antigen engineering through fusion with D8 transmembrane domain may be broadly applicable for enhancing the immune response to antigens delivered by a VACV vector. The recombinant virus described here could also serve as the basis for developing a vaccine against both smallpox and plague.

Original languageEnglish (US)
Pages (from-to)5331-5339
Number of pages9
JournalVaccine
Volume29
Issue number33
DOIs
StatePublished - Jul 26 2011

Keywords

  • Antibody
  • Plague
  • Smallpox
  • Vaccinia

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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