Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins

Vector design strategies for improved vaccine efficacy

Ian J. Caley, Michael R. Betts, Nancy L. Davis, Ronald Swanstrom, Jeffrey A Frelinger, Robert E. Johnston

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

A live virus vaccine vector has been constructed from a molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE). High levels of foreign protein expression are regulated by an additional copy of the 26 S viral subgenomic RNA promoter. The position of this additional promoter and foreign gene in the VEE genome was predicted to have a major influence on expression level of the heterologous protein. Two sites in the genome were tested to determine the optimal site for expression of the matrix/capsid (MA/CA) coding region of human immunodeficiency virus (HIV-1). One vector contained the additional promoter and the MA/CA genes immediately downstream of the VEE E1 gene at the 3' end of the genome. In the second vector, the additional promoter was introduced immediately upstream from the authentic 26 S subgenomic promoter. Significantly higher levels of MA/CA were expressed from the downstream vector compared to the upstream vector. However, the stability of expression for both vectors was similar following passage in baby hamster kidney cells (BHK) cells. In BALB/c mice, the two vectors elicited similar levels of cellular immune responses to MA/CA as determined by bulk cytotoxic T-lymphocyte assays and precursor frequency analysis, but the humoral response induced by the downstream vector was significantly stronger. At 11 months post boosting with the downstream vector, serum antibody levels against HIV MA/CA were undiminished, and MA/CA specific CTLp were detectable in all mice tested. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins.

Original languageEnglish (US)
Pages (from-to)3124-3135
Number of pages12
JournalVaccine
Volume17
Issue number23-24
DOIs
StatePublished - Aug 6 1999
Externally publishedYes

Fingerprint

Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Human Immunodeficiency Virus Proteins
capsid
Capsid
Human immunodeficiency virus 1
HIV-1
Vaccines
vaccines
promoter regions
proteins
Genome
genome
Genes
vector vaccines
cytotoxic T-lymphocytes
genes
viral proteins
Human immunodeficiency virus
mice

Keywords

  • HIV-1 MA/CA
  • Long term immune response
  • VEE
  • Viral vaccine vector

ASJC Scopus subject areas

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

Cite this

Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins : Vector design strategies for improved vaccine efficacy. / Caley, Ian J.; Betts, Michael R.; Davis, Nancy L.; Swanstrom, Ronald; Frelinger, Jeffrey A; Johnston, Robert E.

In: Vaccine, Vol. 17, No. 23-24, 06.08.1999, p. 3124-3135.

Research output: Contribution to journalArticle

Caley, Ian J. ; Betts, Michael R. ; Davis, Nancy L. ; Swanstrom, Ronald ; Frelinger, Jeffrey A ; Johnston, Robert E. / Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins : Vector design strategies for improved vaccine efficacy. In: Vaccine. 1999 ; Vol. 17, No. 23-24. pp. 3124-3135.
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