We recently showed that a new prophylactic vaccination regimen elicited immunity in Indian rhesus macaques that strongly suppressed SIVmac239 infection following mucosal challenge. The effective primeboost vaccination regimen is based on priming with electroporated rDNA encoding the complete SIVmac239 proteome and IL-12 followed by an rAd5 vector boost delivering the same SIV immunogens. Vaccinated animals were able to reduce SIVmac239 genome copies in the blood during chronic infection by a median value of 4 Log units demonstrating a magnitude of control that has been observed rarely before with experimental SIV vaccines. Our HIVRAD Team intends to use this finding to accomplish several important objectives that will advance HIV vaccine design including: 1) determine the nature of the potent immune responses evoked by vaccination and subsequent challenge with homologous SlVmac251 or heterologous SIVsmESSO;2) determine the composition of vaccine immunogens needed to elicit protective immunity;and 3) advance the vaccination regimen towards a viable clinical candidate by developing Ad35 vectors and determining whether they effectively substitute for rAd5. Our Vector Core will provide the rDNA, rAd5, and rAd35 vectors needed to achieve the objectives of this HIVRAD application work plan.

Public Health Relevance

; A new experimental vaccine tested in rhesus macaques generated immunity that strongly suppresses SIV infection following intrarectal virus exposure. Understanding the nature of this effective immunity will provide insight that can be used to design new HIV vaccine candidates. We intend to investigate the characteristics of these potent immune responses and apply this information to the development and testing of new experimental SIV vaccines that can provide the foundation for future HIV vaccine candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI094420-01A1
Application #
8307110
Study Section
Special Emphasis Panel (ZAI1-JBS-A (J1))
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$606,612
Indirect Cost
$74,836
Name
University of Miami School of Medicine
Department
Type
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
de Santana, Marlon G Veloso; Neves, PatrĂ­cia C C; dos Santos, Juliana Ribeiro et al. (2014) Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment. Virology 452-453:202-11