Significance HIV transmission to infants by breast feeding after maternally acquired anti-HIVantibodies decline is well documented. Neonatal vaccination may reduce HIV transmission to children in developing nations where safe alternatives to breast feeding are not available. However, a safe and economical anti-HIV vaccine for neonates must also elicit immunity in the presence of maternal anti-HIV antibodies. Objectives Infection of newborn rhesus macaques with simian immunodeficiency virus is a well-established model for pediatric HIV infection and AIDS. This pilot study evaluated whether proviral DNA from the virulence-attenuated SHIV-33 (virus derived from a molecular clone that consists the HIV-1 SF-33 envelope gene in an otherwise SIV genome) could establish infection in neonates with transplacentally acquired anti-SIV antibodies. Results Three pregnant rhesus macaques were immunized twice intramuscularly during pregnancy with whole-inactivated SIV in adjuvant. After boosting, the dams produced high titer SIV-specific serum antibodies which were transferred to their infants. Four neonates with no anti-SIV antibodies served as controls. All seven infants were inoculated intramuscularly with 100 ug of SHIV-33 proviral DNA within 3 days of birth. Five of the seven infants became infected with SHIV-33 two infants with anti-SIV antibodies and three infants with no SIV antibodies. Virus levels remained low in all but one SHIV-infected animal and none developed any clinical signs of disease by 24 weeks of age. Thus, transplacentally acquired anti-SIV antibodies did not interfere with infection induced by inoculation of neonates with SHIV-33 proviral DNA. These results suggest that a live-attenuated HIV DNA might be developed as a vaccine that could establish infection even in infants with maternally-derived anti-HIV antibodies. Future Directions At 1 year of age each of the five animals infected with live-attenuated SHIV-33 will be inoculated orally with SIVmac239 to determine whether neonatal vaccination can provide long-term protection against virulent SIV. KEYWORDS Pediatric simian AIDS, oral SIV transmission, perinatal HIV transmission, neonatal immunization, live-attenuated vaccine

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-37
Application #
6277926
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
Feng, Jun-Feng; Liu, Jing; Zhang, Lei et al. (2017) Electrical Guidance of Human Stem Cells in the Rat Brain. Stem Cell Reports 9:177-189
Han, Pengcheng; Nielsen, Megan; Song, Melissa et al. (2017) The Impact of Aging on Brain Pituitary Adenylate Cyclase Activating Polypeptide, Pathology and Cognition in Mice and Rhesus Macaques. Front Aging Neurosci 9:180
Pittet, Florent; Johnson, Crystal; Hinde, Katie (2017) Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta). Am J Phys Anthropol 164:457-476
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 :

Showing the most recent 10 out of 408 publications