Passive Transfer of Vaccine-Elicited Antibodies Protects Against SIV in Rhesus Macaques

In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naïve animals against SIVmac251 challenges. The protective signature included multiple antibody functions and correlated with upregulation of interferon pathways in the vaccinated animals. Adoptive transfer of purified IgG from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naïve recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies, even in the absence of virus neutralization. Overall design: We vaccinated 30 rhesus macaques with Ad26-SIV Env/Gag/Pol and SIV Env gp140 protein vaccines and assessed the induction of antibody responses that conformed to a putative protective signature. Animals were primed with 3x1010 viral particles (vp) Ad26-SIVsmE543 Env/Gag/Pol vectors at weeks 0 and 12 and boosted the animals with 3x1010 vp Ad26 vectors combined with 0.25 mg purified SIVmac32H Env gp140 protein with alum adjuvant at weeks 24 and 50. We ranked antibody profiles in all the vaccinated animals based on the protective signature. To define the pathways responsible for the induction of this protective signature, we utilized transcriptomic profiling by RNA-Seq to assess the association between innate immune responses at baseline and following the first protein boost and the subsequent development of the protective signature