Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.
Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.
复制标题
DOI：
10.1038/ncomms15711
复制
发表时间：
2017-06-08
影响因子：
16.6
通讯作者：
Haynes BF
中科院分区：
文献类型：
--
作者：
Bradley T;Pollara J;Santra S;Vandergrift N;Pittala S;Bailey-Kellogg C;Shen X;Parks R;Goodman D;Eaton A;Balachandran H;Mach LV;Saunders KO;Weiner JA;Scearce R;Sutherland LL;Phogat S;Tartaglia J;Reed SG;Hu SL;Theis JF;Pinter A;Montefiori DC;Kepler TB;Peachman KK;Rao M;Michael NL;Suscovich TJ;Alter G;Ackerman ME;Moody MA;Liao HX;Tomaras G;Ferrari G;Korber BT;Haynes BF
重组痘病毒（ALVAC）和重组HIV-1 gp 120亚型B/亚型E（B/E）蛋白的RV 144泰国试验HIV-1疫苗显示了31%的疫苗有效性。在这里，我们设计了ALVAC/五价B/E/E/E/E疫苗，以增加免疫原中gp 120基序的多样性，从而引发更广泛的抗体应答并增强保护。我们发现用五价疫苗对恒河猴进行免疫接种可使55%的五价疫苗免疫的恒河猴免受猴-人免疫缺陷病毒（SHIV）的攻击。抗体应答的系统血清学鉴定了与HIV感染细胞结合的血浆抗体、峰值ADCC抗体滴度、NK细胞介导的ADCC和NK细胞中抗体介导的MIP-1β活化，作为最能预测五价疫苗改善的感染风险降低的4个免疫学参数。因此，包含额外的gp 120免疫原的痘初免/蛋白加强方案可以增强抗体应答，并增强保护恒河猴免受SHIV攻击。以前的人类HIV-1疫苗临床试验，加强与HIV包膜蛋白从两个菌株，证明了适度的疫苗效力。在这里，布拉德利等人表明，五价HIV包膜蛋白加强免疫可以提高非人灵长类动物对病毒攻击的保护，他们还鉴定了保护的免疫相关性。
The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian–human immunodeficiency virus (SHIV) challenge. Systems serology of the antibody responses identifies plasma antibody binding to HIV-infected cells, peak ADCC antibody titres, NK cell-mediated ADCC and antibody-mediated activation of MIP-1β in NK cells as the four immunological parameters that best predict decreased infection risk that are improved by the pentavalent vaccine. Thus inclusion of additional gp120 immunogens to a pox-prime/protein boost regimen can augment antibody responses and enhance protection from a SHIV challenge in rhesus macaques. A previous human HIV-1 vaccine clinical trial, boosting with HIV envelope protein from two strains, demonstrated moderate vaccine efficacy. Here, Bradley et al. show that a pentavalent HIV envelope protein boost improves protection from viral challenge in non-human primates and they identify immune correlates of protection.