Significance These studies should provide insight into the use of recombinant Listeriamonocytogenes for generating anti-viral mucosal immunity in primates. Because live-attenuated bacterial vaccines are currently used in people, this work may lead directly to a vaccine that can be used to prevent the sexual transmission of HIV. Objectives This project will use the SIV/macaque model to test the efficacy of immunization with recombinant Listeria monocytogenes, an attenuated intracellular bacterium. Initial studies will characterize the pathogenicity in rhesus monkeys of attenuated listeria vectors, and immune responses of rhesus macaques to the proteins of SIV expressed by these vectors. Anti-SIV cytotoxic T lymphocyte responses in peripheral blood, lymphoid tissues and the genital mucosa will be quantified. And systemic and secretory (including vaginal) immune responses to the immunizations will be characterized using isotype and SIV-specific assays. The immune response between each boost will be measured in order to assess which components of the immunization protocol are essential to obtain a protective response. If a strong local immune response is produced by the immunization strategy, the animals will be vaginally challenged with virulent SIV. Results Initial immunization of two juvenile monkeys with listeria expressing the SIV gag gene was found to be nontoxic, with doses ranging from 105 to 108 colony forming units given intramuscularly. These monkeys became infected with SIV after oral challenge, but the viral loads were relatively low in blood and lymph node. Four more monkeys have been immunized with control or SIV-expressing listeria based on the initial experiment, and they will be challenged orally with SIV 3 weeks after the third immunization. Future Directions Of particular interest is whether these intracellular bacteria are capable of inducing cellular immune responses in the genital tract. KEYWORDS SIV, vaccine, cell - mediated immunity;

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-37
Application #
6277929
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
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
Rose, Destanie R; Careaga, Milo; Van de Water, Judy et al. (2017) Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain Behav Immun 63:60-70
Jensen, Kara; Dela Pena-Ponce, Myra Grace; Piatak Jr, Michael et al. (2017) Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine. Clin Vaccine Immunol 24:

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