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.
; 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.
|Shin, Young C; Bischof, Georg F; Lauer, William A et al. (2018) A recombinant herpesviral vector containing a near-full-length SIVmac239 genome produces SIV particles and elicits immune responses to all nine SIV gene products. PLoS Pathog 14:e1007143|
|Magnani, Diogo M; Rogers, Thomas F; Maness, Nicholas J et al. (2018) Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques. Nat Commun 9:1624|
|Magnani, Diogo M; Ricciardi, Michael J; Bailey, Varian K et al. (2017) Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys. Mol Ther 25:2323-2331|
|Magnani, Diogo M; Rogers, Thomas F; Beutler, Nathan et al. (2017) Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques. Sci Transl Med 9:|
|Rainho, Jennifer N; Martins, Mauricio A; Cunyat, Francesc et al. (2015) Nef Is Dispensable for Resistance of Simian Immunodeficiency Virus-Infected Macrophages to CD8+ T Cell Killing. J Virol 89:10625-36|
|de Santana, Marlon G Veloso; Neves, Patrícia 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|
|Neves, Patricia C C; Santos, Juliana R; Tubarao, Luciana N et al. (2013) Early IFN-gamma production after YF 17D vaccine virus immunization in mice and its association with adaptive immune responses. PLoS One 8:e81953|