In recent experiments, combination DNA priming/protein boost vaccination regimens have elicited protection against challenge with chimeric SHIV in juvenile and neonatal vaccine recipient macaques. The experiments propose din Project 3 will test whether protection against a SHIV construct encoding a clade C env gene (SHIVenvC) can be achieved in both juvenile and neonatal macaques using a DNA prime/protein boost schedule of vaccination. The main points of Specific Aims of Project 3 are: 1. To test the immunogenicity of codon-optimized HIV-I clade C env- and SIV gag-pol-expressing plasmids in mice (Specific Aim 1a). Nest, we will test the safety and immuno genicity of the most immunogenic DNA plasmids in juvenile (Specific Aim 1b) and neonatal macaques (Specific Aim 1c) using a DNA prime/protein boost strategy. We will vaccination against both HIV-I clade C env gp160 and SIV Gag-Pol. 2. To test whether DNA prime/protein boost can induce protective immunity in juvenile macaques against i.v. challenge with homologous SHIVenvC1. Immunized juveniles from Specific Aim 1b will be challenged i.v. with SHIVenvC1. Viral load will be assessed by co- cultivation of PBMC and by RT-PCR of plasma. Pathogenicity will also be assessed. 3. To test whether DNA prime/protein boost can induced protective immunity in macaque infants vaccinated as newborns against oral challenge with SHIVenvC1. As a model for postnatal mil borne virus transmission immunized animals from Specific Aim 1c will be challenged at one year of age by oral inoculation with SHIVenvC1. 4. To test if protected animals in Specific Aims 2b and 3b have developed broad, protective immunity against divergent SHIV isolates expressing heterologous Env glycoproteins. 5. To test whether active + passive immunization can induce protection against systemic infection for infant rhesus macaques challenged orally at birth with SHIVenvCV1. The experimental results of Project 3 are integral to the overall goal of the Program Project to develop passive + active immunization to prevent virus transmission at birth and through breast feeding. The findings of this Project will have clinical relevance for HIV clade C endemic areas of sub- Saharan Africa.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI048240-02
Application #
6474984
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2001-06-01
Project End
2002-05-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
$171,469
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
Tokatlian, Talar; Kulp, Daniel W; Mutafyan, Andrew A et al. (2018) Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci Rep 8:16527
Ruprecht, Ruth M; Lakhashe, Samir K (2017) Antibody-mediated immune exclusion of HIV. Curr Opin HIV AIDS 12:222-228
Ruprecht, Ruth M (2017) Anti-HIV Passive Immunization: New Weapons in the Arsenal. Trends Microbiol 25:954-956
Schneider, Jeffrey R; Carias, Ann M; Bastian, Arangaserry R et al. (2017) Long-term direct visualization of passively transferred fluorophore-conjugated antibodies. J Immunol Methods 450:66-72
Kulkarni, Viraj; Ruprecht, Ruth M (2017) Mucosal IgA Responses: Damaged in Established HIV Infection-Yet, Effective Weapon against HIV Transmission. Front Immunol 8:1581
Sholukh, Anton M; Watkins, Jennifer D; Vyas, Hemant K et al. (2015) Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge. Vaccine 33:2086-95
Lakhashe, Samir K; Byrareddy, Siddappa N; Zhou, Mingkui et al. (2014) Multimodality vaccination against clade C SHIV: partial protection against mucosal challenges with a heterologous tier 2 virus. Vaccine 32:6527-36
Zhou, Mingkui; Ruprecht, Ruth M (2014) Are anti-HIV IgAs good guys or bad guys? Retrovirology 11:109
Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan et al. (2014) Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose. Retrovirology 11:8
Bachler, Barbara C; Humbert, Michael; Lakhashe, Samir K et al. (2013) Live-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremia. Retrovirology 10:63

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