Significance Simian immunodeficiency virus (SIV) infection of macaques is a unique model for human immunodeficiency virus (HIV) infection and vaccine development. Objective The use of IFN-( and other lymphokines to enhance the safety and efficacy of live attenuated vaccines for AIDS is the major and long term objective of these projects. Results We constructed and characterized a number of SIV vectors with a deletion in the nef gene (SIV(nef) and expressing interferon-( under SV40 early promotor or SIV 5?LTR (SIVHyIFN). Rhesus macaques vaccinated with SIVHyIFN have a lower viral load than a group similarly immunized with SIV(nef. Viral loads remained low in the SIVHyIFN -vaccinated group even though SIV expressing IFN-( could not be isolated after 6 weeks post-immunization in these animals. All immunized and two naive control macaques became infected when challenged with virulent SIVmac251 at 25 weeks post-vaccination. In contrast to the two naive controls that died by 12 and 18 weeks post-challenge, post-challenge cell-associated virus load was significantly lower in SIVHyIFN-immunized animals than in the group vaccinated with SIV(nef. Also, the oral administration of SIVHyIFN was non-pathogenic for newborn macaques and induced protective immunity against challenge with virulent SIVmac251 in one macaque that had low level sporadic SIVHyIFN viremia. These findings indicate that cytokine-expressing viruses can provide a novel approach for development of safe and efficacious live attenuated vaccines for AIDS. Future Directions SIV with a deletion in the nef gene and expressing IFN-( is safer and more efficacious for both neonatal and juvenile macaques against simian AIDS. The next generation recombinant SIV vectors, that express IFN-( and have stable genomes, are being constructed for developing safer and efficacious live-attenuated vaccines for AIDS. KEYWORDS AIDS vaccines, recombinant SIV vectors, IFN-(, lymphokines, immune response, macaques;

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-37
Application #
6277953
Study Section
Project Start
1998-05-01
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Comrie, Alison E; Gray, Daniel T; Smith, Anne C et al. (2018) Different macaque models of cognitive aging exhibit task-dependent behavioral disparities. Behav Brain Res 344:110-119
Day, George Q; Ng, Jillian; Oldt, Robert F et al. (2018) DNA-based Determination of Ancestry in Cynomolgus Macaques (Macaca fascicularis). J Am Assoc Lab Anim Sci 57:432-442
Carroll, Timothy D; Jegaskanda, Sinthujan; Matzinger, Shannon R et al. (2018) A Lipid/DNA Adjuvant-Inactivated Influenza Virus Vaccine Protects Rhesus Macaques From Uncontrolled Virus Replication After Heterosubtypic Influenza A Virus Challenge. J Infect Dis 218:856-867
Midic, Uros; VandeVoort, Catherine A; Latham, Keith E (2018) Determination of single embryo sex in Macaca mulatta and Mus musculus RNA-Seq transcriptome profiles. Physiol Genomics 50:628-635
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Ciupe, Stanca M; Miller, Christopher J; Forde, Jonathan E (2018) A Bistable Switch in Virus Dynamics Can Explain the Differences in Disease Outcome Following SIV Infections in Rhesus Macaques. Front Microbiol 9:1216
Kyle, Colin T; Stokes, Jared; Bennett, Jeffrey et al. (2017) Cytoarchitectonically-driven MRI atlas of nonhuman primate hippocampus: Preservation of subfield volumes in aging. Hippocampus :
Moadab, Gilda; Bliss-Moreau, Eliza; Bauman, Melissa D et al. (2017) Early amygdala or hippocampus damage influences adolescent female social behavior during group formation. Behav Neurosci 131:68-82
Seil, Shannon K; Hannibal, Darcy L; Beisner, Brianne A et al. (2017) Predictors of insubordinate aggression among captive female rhesus macaques. Am J Phys Anthropol 164:558-573
Zhang, Xinjun; Kanthaswamy, Sree; Trask, Jessica S et al. (2017) Genetic Characterization of a Captive Colony of Pigtailed Macaques (Macaca nemestrina). J Am Assoc Lab Anim Sci 56:390-395

Showing the most recent 10 out of 408 publications