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Multigene DNA Priming-Boosting Vaccines Protect Macaques from Acute CD4+-T-Cell Depletion after Simian-Human Immunodeficiency Virus SHIV89.6P Mucosal Challenge
- Source :
- Journal of Virology. 77:11563-11577
- Publication Year :
- 2003
- Publisher :
- American Society for Microbiology, 2003.
-
Abstract
- We evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus SHIV89.6P inMacaca nemestrina. Each regimen included gene gun delivery of a DNA vaccine expressing all SHIV89.6 genes plus Env gp160 of SHIV89.6P. Additional components were two recombinant vaccinia viruses, expressing SHIV89.6 Gag-Pol or Env gp160, and inactivated SHIV89.6 virus. We compared (i) DNA priming/DNA boosting, (ii) DNA priming/inactivated virus boosting, (iii) DNA priming/vaccinia virus boosting, and (iv) vaccinia virus priming/DNA boosting versus sham vaccines in groups of 6 macaques. Prechallenge antibody responses to Env and Gag were strongest in the groups that received vaccinia virus priming or boosting. Cellular immunity to SHIV89.6 peptides was measured by enzyme-linked immunospot assay; strong responses to Gag and Env were found in 9 of 12 vaccinia virus vaccinees and 1 of 6 DNA-primed/inactivated-virus-boosted animals. Vaccinated macaques were challenged intrarectally with 50 50% animal infectious doses of SHIV89.6P 3 weeks after the last immunization. All animals became infected. Five of six DNA-vaccinated and 5 of 6 DNA-primed/particle-boosted animals, as well as all 6 controls, experienced severe CD4+-T-cell loss in the first 3 weeks after infection. In contrast, DNA priming/vaccinia virus boosting and vaccinia virus priming/DNA boosting vaccines both protected animals from disease: 11 of 12 macaques had no loss of CD4+T cells or moderate declines. Virus loads in plasma at the set point were significantly lower in vaccinia virus-primed/DNA-boosted animals versus controls (P= 0.03). We conclude that multigene vaccines delivered by a combination of vaccinia virus and gene gun-delivered DNA were effective against SHIV89.6P viral challenge inM. nemestrina.
- Subjects :
- CD4-Positive T-Lymphocytes
Cellular immunity
viruses
Immunology
Immunization, Secondary
Simian Acquired Immunodeficiency Syndrome
Priming (immunology)
HIV Infections
Vaccinia virus
Biology
Antibodies, Viral
medicine.disease_cause
complex mixtures
Microbiology
Virus
HIV Envelope Protein gp160
Gene gun
law.invention
Viral Proteins
chemistry.chemical_compound
law
Virology
Vaccines and Antiviral Agents
Vaccines, DNA
medicine
Animals
Humans
AIDS Vaccines
Immunity, Cellular
Boosting (doping)
Cd4 t cell
Errata
SAIDS Vaccines
Simian human immunodeficiency virus
Biolistics
Simian immunodeficiency virus
chemistry
Insect Science
HIV-1
Recombinant DNA
Immunization
Simian Immunodeficiency Virus
Macaca nemestrina
Vaccinia
DNA
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....7759b66290ac802b5301c06a3d6c047b