Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia.
Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia.
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DOI：
10.1016/j.vaccine.2011.02.066
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发表时间：
2011-04-12
期刊：
影响因子：
5.5
通讯作者：
Robert-Guroff, Marjorie
中科院分区：
文献类型：
--
作者：
Brocca-Cofano, Egidio;McKinnon, Katherine;Demberg, Thorsten;Venzon, David;Hidajat, Rachmat;Xiao, Peng;Daltabuit-Test, Mara;Patterson, L. Jean;Robert-Guroff, Marjorie
关键词：
有效的HIV疫苗需要强的全身和粘膜、细胞和体液免疫。许多非人类灵长类动物研究已经研究了记忆T细胞，但没有研究记忆B细胞。体液免疫记忆是由长寿命的抗体分泌浆细胞和记忆B细胞在再次暴露于免疫抗原后分化为短寿命的浆母细胞介导的。在这里，我们研究了免疫恒河猴的记忆B细胞。用CD 40配体、IL-21和CpG多克隆刺激PBMC以诱导B细胞增殖和分化为抗体分泌细胞（ASC）。流式细胞术用于表型分型和通过CFSE稀释评价增殖。通过ELISPOT定量B细胞应答。使用接种疫苗的精英控制猕猴的PBMC建立了方法，这些猕猴表现出强大的多功能抗体活性。随后，在SIV和SHIV攻击前和攻击后，回顾性地评价由两种复制型Ad-重组初免/包膜加强方案引发的记忆B细胞。疫苗方案诱导SIV和HIV Env特异性IgG和伊加记忆B细胞。在攻击之前，伊加记忆B细胞比IgG记忆B细胞更多，反映了粘膜引发免疫。激发前和激发后的记忆B细胞与功能性抗体应答相关，包括抗体依赖性细胞毒性（ADCC）、抗体依赖性细胞介导的病毒抑制（ADCVI）和转胞吞抑制。攻击后，Env特异性IgG和伊加记忆B细胞与慢性病毒血症减少相关。我们的结论是，我们的初免/加强方案引起的功能性抗体应答被有效地纳入记忆B细胞库，在那里它们有助于再次暴露于免疫抗原后控制病毒血症。
An effective HIV vaccine requires strong systemic and mucosal, cellular and humoral immunity. Numerous non-human primate studies have investigated memory T cells, but not memory B cells. Humoral immunologic memory is mediated by long-lived antibody-secreting plasma cells and differentiation of memory B cells into short-lived plasma blasts following re-exposure to immunizing antigen. Here we studied memory B cells in vaccinated rhesus macaques. PBMC were stimulated polyclonally using CD40 Ligand, IL-21 and CpG to induce B cell proliferation and differentiation into antibody secreting cells (ASC). Flow cytometry was used for phenotyping and evaluating proliferation by CFSE dilution. B cell responses were quantified by ELISPOT. Methodology was established using PBMC of vaccinated elite-controller macaques that exhibited strong, multi-functional antibody activities. Subsequently, memory B cells elicited by two replicating Ad-recombinant prime/envelope boost regimens were retrospectively evaluated pre- and post- SIV and SHIV challenges. The vaccine regimens induced SIV and HIV Env-specific IgG and IgA memory B cells. Prior to challenge, IgA memory B cells were more numerous than IgG memory B cells, reflecting the mucosal priming immunizations. Pre- and post-challenge memory B cells were correlated with functional antibody responses including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI) and transcytosis inhibition. Post-challenge, Env-specific IgG and IgA memory B cells were correlated with reduced chronic viremia. We conclude that functional antibody responses elicited by our prime/boost regimen were effectively incorporated into the memory B cell pool where they contributed to control of viremia following re-exposure to the immunizing antigen.
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