Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations.
Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations.
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DOI：
10.1371/journal.pone.0196397
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
RV305 Study Group
中科院分区：
文献类型：
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作者：
Akapirat S;Karnasuta C;Vasan S;Rerks-Ngarm S;Pitisuttithum P;Madnote S;Savadsuk H;Rittiroongrad S;Puangkaew J;Phogat S;Tartaglia J;Sinangil F;de Souza MS;Excler JL;Kim JH;Robb ML;Michael NL;Ngauy V;O'Connell RJ;Karasavvas N;RV305 Study Group
性传播是人体免疫缺陷病毒（艾滋病毒）大流行病的主要驱动因素。了解HIV疫苗在粘膜表面诱导的免疫反应可以产生关于保护机制的假设，并可能影响疫苗的开发。RV 144（ClinicalTrials.gov NCT 00223080）有效性试验显示了对HIV感染的保护作用，但未采集粘膜样本，因此，粘膜抗体对预防HIV-1感染的作用尚不清楚。在这里，我们报告了重组gp 120包膜和抗原，包括可变的一个和两个环支架抗原（gp 70 V1 V2）先前显示与RV 144的风险相关的抗体反应的产生，幅度和持久性。我们评估了未感染HIV的RV 144疫苗接种者的宫颈阴道粘液（CVM）、精浆（SP）和直肠分泌物（RS）中对gp 120 A244 gD和gp 70 V1 V2 92 TH 023（均为CRF 01_AE）和病例A2（亚型B）的抗体应答，这些接种者被随机分配接受ALVAC-HIV/AIDSVAX®B/E、AIDSVAX®B/E或ALVAC-HIV单药的两次晚期加强，分别在0个月和6个月。晚期疫苗加强使AIDSVAX®B/E和ALVAC-HIV/AIDSVAX ® B/E CVM中的IgG几何平均滴度（GMT）增加至gp 120 A244 gD（分别为28和17倍），其次是SP和RS。在第一次加强后两周，在AIDSVAX®B/E和ALVAC-HIV/AIDSVAX®B/E CVM（11-17倍）和SP（2倍）中针对gp 70 V1 V2 92 TH 023的IgG增加。仅在AIDSVAX®B/E和ALVAC-HIV/AIDSVAX®B/E CVM中检测到针对病例A2的IgG。针对gp 120 A244 gD（CVM，SP，RS）、gp 70 V1 V2 92 TH 023（CVM，SP）和Case A2（CVM）的粘蛋白IgG与血浆IgG水平相关（p<0.001）。虽然IgG应答的幅度在加强后下降，但在最终疫苗接种后，CVM中的抗gp 120 A244 gD IgG应答持续12个月。进一步研究肛门生殖器分泌物中包膜特异性抗体（IgG和二聚体伊加）的定位、持久性和大小将有助于确定它们在预防粘膜HIV获得中的作用。
Sexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2) previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE) and Case A2 (subtype B) in cervico-vaginal mucus (CVM), seminal plasma (SP) and rectal secretions (RS) from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT) to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively), followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11–17 fold) and SP (2 fold) two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS), gp70V1V2 92TH023 (CVM, SP), and Case A2 (CVM) correlated with plasma IgG levels (p<0.001). Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA) in anogenital secretions will help determine their role in preventing mucosal HIV acquisition.