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UV-inactivated vaccinia virus (VV) in a multi-envelope DNA-VV-protein (DVP) HIV-1 vaccine protects macaques from lethal challenge with heterologous SHIV.
- Source :
-
Vaccine [Vaccine] 2012 May 02; Vol. 30 (21), pp. 3188-95. Date of Electronic Publication: 2012 Mar 14. - Publication Year :
- 2012
-
Abstract
- The pandemic of HIV-1 has continued for decades, yet there remains no licensed vaccine. Previous research has demonstrated the effectiveness of a multi-envelope, multi-vectored HIV-1 vaccine in a macaque-SHIV model, illustrating a potential means of combating HIV-1. Specifically, recombinant DNA, vaccinia virus (VV) and purified protein (DVP) delivery systems were used to vaccinate animals with dozens of antigenically distinct HIV-1 envelopes for induction of immune breadth. The vaccinated animals controlled disease following challenge with a heterologous SHIV. This demonstration suggested that the antigenic cocktail vaccine strategy, which has succeeded in several other vaccine fields (e.g. pneumococcus), might also succeed against HIV-1. The strategy remains untested in an advanced clinical study, in part due to safety concerns associated with the use of replication-competent VV. To address this concern, we designed a macaque study in which psoralen/ultraviolet light-inactivated VV (UV VV) was substituted for replication-competent VV in the multi-envelope DVP protocol. Control animals received a vaccine encompassing no VV, or no vaccine. All VV vaccinated animals generated an immune response toward VV, and all vaccinated animals generated an immune response toward HIV-1 envelope. After challenge with heterologous SHIV 89.6P, animals that received replication-competent VV or UV VV experienced similar outcomes. They exhibited reduced peak viral loads, maintenance of CD4+ T cell counts and improved survival compared to control animals that received no VV or no vaccine; there were 0/15 deaths among all animals that received VV and 5/9 deaths among controls. Results define a practical means of improving VV safety, and encourage advancement of a promising multi-envelope DVP HIV-1 vaccine candidate.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- AIDS Vaccines administration & dosage
Animals
CD4 Lymphocyte Count
Macaca
Survival Analysis
Vaccines, Inactivated administration & dosage
Vaccines, Inactivated immunology
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic immunology
Viral Load
AIDS Vaccines immunology
Genetic Vectors
HIV-1 immunology
Simian Acquired Immunodeficiency Syndrome prevention & control
Vaccinia virus genetics
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 30
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 22425790
- Full Text :
- https://doi.org/10.1016/j.vaccine.2012.03.001