Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cell. 2020 Oct 1;183(1):185-196.e14. doi: 10.1016/j.cell.2020.08.033.
Several HIV-1 and SIV vaccine candidates have shown partial protection against viral challenges in rhesus macaques. However, the protective efficacy of vaccine-elicited polyclonal antibodies has not previously been demonstrated in adoptive transfer studies in nonhuman primates. In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naive animals against SIVmac251 challenges. We vaccinated 30 rhesus macaques with Ad26-SIV Env/Gag/Pol and SIV Env gp140 protein vaccines and assessed the induction of antibody responses and a putative protective signature. This signature included multiple antibody functions and correlated with upregulation of interferon pathways in vaccinated animals. Adoptive transfer of purified immunoglobulin G (IgG) from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naive recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies in this model, even in the absence of virus neutralization.
几种 HIV-1 和 SIV 疫苗候选物已显示出在恒河猴中对病毒挑战的部分保护作用。然而，以前在非人类灵长类动物的过继转移研究中尚未证明疫苗诱导的多克隆抗体的保护效力。在这项研究中，我们表明，从接种疫苗的猕猴中纯化的抗体的被动转移可以保护幼稚动物免受 SIVmac251 的挑战。我们用 Ad26-SIV Env/Gag/Pol 和 SIV Env gp140 蛋白疫苗接种了 30 只恒河猴，并评估了抗体反应和假定的保护性特征的诱导。该特征包括多种抗体功能，并与接种动物中干扰素途径的上调相关。具有最强保护特征的接种动物中纯化免疫球蛋白 G（IgG）的过继转移为幼稚受者恒河猴提供了对 SIVmac251 挑战的部分保护。这些数据证明了在该模型中纯化的疫苗诱导的抗病毒抗体的保护效力，即使在没有病毒中和的情况下也是如此。
