Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
J Virol. 2018 Jul 17;92(15). doi: 10.1128/JVI.00537-18. Print 2018 Aug 1.
Vaccine-elicited immunoglobulin G (IgG) has been shown to be important for protection against simian-human immunodeficiency virus (SHIV) infection in rhesus monkeys. However, it remains unclear whether vaccine-elicited IgA responses are beneficial or detrimental for protection. In this study, we evaluated the kinetics, magnitude, breadth, and linear epitope specificities of vaccine-elicited IgG and IgA responses in serum and mucosal secretions following intramuscular immunization with adenovirus 26 (Ad26) prime, Env protein boost vaccination regimens. The systemic and mucosal antibody responses exhibited kinetics similar to those of the serum antibody responses but lower titers than the serum antibody responses. Moreover, the IgG and IgA responses were correlated, both in terms of the magnitude of the responses and in terms of the antibody specificities against linear human immunodeficiency virus type 1 (HIV-1) Env, Gag, and Pol epitopes. These data suggest that IgG and IgA responses are highly coordinated in both peripheral blood and mucosal compartments following Ad26/Env vaccination in rhesus monkeys. Vaccine-elicited IgG responses are important for protection against simian-human immunodeficiency virus (SHIV) infection in nonhuman primates. However, much less is known about the role and function of IgA, despite it being the predominant antibody in mucosal sites. There is debate as to whether HIV-1-specific IgA responses are beneficial or detrimental, since serum anti-Env IgA titers were shown to be inversely correlated with protection in the RV144 clinical trial. We thus assessed vaccine-elicited IgG and IgA antibody responses in peripheral blood and mucosal secretions following vaccination with the Ad26/Env vaccine.
疫苗诱导的免疫球蛋白 G(IgG)已被证明对预防恒河猴感染猴免疫缺陷病毒(SHIV)至关重要。然而,疫苗诱导的 IgA 反应是否有利于保护仍不清楚。在这项研究中,我们评估了腺病毒 26(Ad26)初免、Env 蛋白加强免疫方案肌肉内免疫后血清和粘膜分泌物中疫苗诱导的 IgG 和 IgA 反应的动力学、幅度、广度和线性表位特异性。系统和粘膜抗体反应的动力学与血清抗体反应相似,但滴度低于血清抗体反应。此外,IgG 和 IgA 反应在反应幅度和针对线性人类免疫缺陷病毒 1(HIV-1)Env、Gag 和 Pol 表位的抗体特异性方面呈正相关。这些数据表明,在恒河猴 Ad26/Env 疫苗接种后,外周血和粘膜隔室中 IgG 和 IgA 反应高度协调。疫苗诱导的 IgG 反应对预防非人类灵长类动物中的猴免疫缺陷病毒(SHIV)感染很重要。然而,尽管 IgA 是粘膜部位的主要抗体,但对其作用和功能的了解要少得多。关于 HIV-1 特异性 IgA 反应是有益还是有害存在争议,因为在 RV144 临床试验中显示血清抗 Env IgA 滴度与保护呈负相关。因此,我们在接种 Ad26/Env 疫苗后评估了外周血和粘膜分泌物中疫苗诱导的 IgG 和 IgA 抗体反应。