beneath the table to the abstract. Use the Word Count cmd under Utilites menu for counting Significance Clinical disease in HIV-infected infants is similar to that in HIV-infected adults although pediatric AIDS has a more rapid clinical course with a higher mortality rate. HIV-specific cytotoxic T lymphocytes are proposed to play an important role in containment of HIV in infected individuals. HIV-specific cytotoxic T lymphocytes (CTL) responses are relatively weak in HIV-infected children compared to adults which may explain the more rapid disease course in pediatric AIDS. Immunization of infants born to HIV-infected women to elicit HIV-specific CTL has been proposed as an anti-HIV vaccine or immune-based therapy. Objectives Infection of newborn rhesus macaques with simian immunodeficiency virus is a well-established model for pediatric HIV infection and AIDS. This study will determine whether an immunization regimen (non-replicating plasmid DNA and modified vaccinia Ankara, MVA) can elicit SIV-specific CTL in neonates that express a well-characterized allele of the Macaca mulatta major histocompatibility complex (MHC) class I designated MamuA*01. Results PCR-based MHC class I typing identified adult rhesus macaques in the CRPRC indoor breeding colony expressing the MamuA*01 allele which were mated to produce five MamuA*01 infants. Autologous transformed B cell lines were prepared for each of the five infants to permit assay of SIV-specific CTL after vaccination. At 7-9 months of age each of the five MamuA*01 animals will be vaccinated (plasmid DNA and MVA that encode SIV CTL epitopes) to determine whether vaccination elicits SIV-specific CTL that can protect against oral challenge with virulent SIV. Future Directions MamuA*01 adult male rhesus will be vaccinated to elicit SIV-specific CTL; after in vitro expansion, SIV-CTL will be transfused into Mamu A*01 newborns sired by the male. This transfer of CTL from a vaccinated animal to naove animals requires identical MHC class I alleles and will test whether SIV-specific CTL alone can protect against oral SIV challenge. KEY WORDS pediatric AIDS, oral SIV transmission, perinatal HIV transmission, neonatal immunization, DNA/MVA vaccine, major histocompatibility complex class I locus, adoptive transfer of T lymphocytes, virus-specific CTL FUNDING NIH Grants RR00169 and AI039109, E. Glaser Pediatric AIDS Foundation Scientist Award 33-98

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-38
Application #
6116680
Study Section
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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