Similar Epitope Specificities of IgG and IgA Antibodies Elicited by Ad26 Vector Prime, Env Protein Boost Immunizations in Rhesus Monkeys.
Similar Epitope Specificities of IgG and IgA Antibodies Elicited by Ad26 Vector Prime, Env Protein Boost Immunizations in Rhesus Monkeys.
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DOI：
10.1128/jvi.00537-18
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发表时间：
2018-08-01
影响因子：
5.4
通讯作者：
Barouch DH
中科院分区：
文献类型：
--
作者：
Kang ZH;Bricault CA;Borducchi EN;Stephenson KE;Seaman MS;Pau M;Schuitemaker H;van Manen D;Wegmann F;Barouch DH
疫苗诱导的免疫球蛋白G（IgG）已被证明是重要的保护对猴-人免疫缺陷病毒（SHIV）感染的恒河猴。然而，目前还不清楚疫苗引起的伊加反应是有益还是有害的保护。在这项研究中，我们评估了肌肉注射腺病毒26（Ad 26）prime，Env蛋白加强免疫接种方案后，血清和粘膜分泌物中疫苗引起的IgG和伊加应答的动力学，幅度，宽度和线性表位特异性。全身和粘膜抗体反应表现出与血清抗体反应相似的动力学，但滴度低于血清抗体反应。此外，IgG和伊加反应是相关的，无论是在反应的幅度和对线性人类免疫缺陷病毒1型（HIV-1）的Env，Gag和Pol表位的抗体特异性。这些数据表明，IgG和伊加的反应是高度协调的外周血和粘膜隔室后，在恒河猴的Ad 26/Env疫苗接种。疫苗诱导的IgG应答对于保护非人灵长类动物免受猴-人免疫缺陷病毒（SHIV）感染非常重要。然而，对伊加的作用和功能知之甚少，尽管它是粘膜部位的主要抗体。关于HIV-1特异性伊加应答是有益的还是有害的存在争议，因为在RV 144临床试验中显示血清抗Env伊加滴度与保护呈负相关。因此，我们评估了疫苗引起的IgG和伊加抗体反应的外周血和粘膜分泌物接种后的Ad 26/Env疫苗。
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. IMPORTANCE 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.