title: Protection by SIV VLP DNA prime/protein boost following mucosal SIV challenge is markedly enhanced by IL-12/GM-CSF co-administration.
abstract: The ever increasing number of people infected by human immunodeficiency virus (HIV) throughout the world renders the development of effective vaccines an urgent priority. Herein, we report on an attempt to induce and enhance antiviral responses using a deoxyribonucleic acid (DNA) prime/virus-like particles (VLP) protein boost strategy adjuvanted with interleukin (IL)-12/GM-CSF in rhesus macaques challenged with simian immunodeficiency virus (SIV). Thus, groups of monkeys were administered three consecutive doses of pVecB7 a plasmid expressing VLP with or without plasmids expressing IL-12 and GM-CSF at weeks 0, 13 and 26. The VLP boost was administered at week 39 with or without IL-12. All monkeys were challenged intrarectally with SIVsmE660 2 months following the protein boost. All except one immunized monkey became infected. While all immunized monkeys showed a marked reduction of acute viral peaks, reduction of viral load set points was only achieved in groups whose prime-boost immunizations were supplemented with IL-12/GM-CSF (prime) and/or with IL-12 (boost). Control of viremia correlated with lack of disease progression and survival. Detection of virus in rectal washes at 1 year post-challenge was only successful in monkeys whose immunizations did not include cytokine adjuvant, but these loads did not correlate with plasma viral loads. In summary, use of IL-12 and/or GM-CSF was shown to provide significant differences in the outcome of SIV challenge of prime/boost immunized monkeys.
authors.affiliation: Department of Microbiology and Medical Zoology and Caribbean Primate Research Center, Unit of Comparative Medicine, University of Puerto Rico School of Medicine, San Juan, PR 00936, USA.
authors.forename: E
authors.initials: E
authors.lastname: O'Neill
authors.forename: I
authors.initials: I
authors.lastname: Martinez
authors.forename: F
authors.initials: F
authors.lastname: Villinger
authors.forename: M
authors.initials: M
authors.lastname: Rivera
authors.forename: S
authors.initials: S
authors.lastname: Gascot
authors.forename: C
authors.initials: C
authors.lastname: Colon
authors.forename: T
authors.initials: T
authors.lastname: Arana
authors.forename: M
authors.initials: M
authors.lastname: Sidhu
authors.forename: R
authors.initials: R
authors.lastname: Stout
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: M
authors.initials: M
authors.lastname: Martinez
authors.forename: A A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Z R
authors.initials: ZR
authors.lastname: Israel
authors.forename: E
authors.initials: E
authors.lastname: Kraiselburd
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D015996:Survival Rate; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor