五价 HIV-1 疫苗可预防猴免疫缺陷病毒攻击。

Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.

机构信息

Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

出版信息

Nat Commun. 2017 Jun 8;8:15711. doi: 10.1038/ncomms15711.

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.

RV144 泰国试验的 HIV-1 重组痘病毒（ALVAC）和重组 HIV-1 gp120 亚类 B/亚类 E（B/E）蛋白疫苗显示出 31%的疫苗效力。在这里，我们设计了一种 ALVAC/五价 B/E/E/E/E 疫苗，以增加免疫原中 gp120 基序的多样性，从而引发更广泛的抗体反应并增强保护作用。我们发现，用五价疫苗免疫恒河猴可使 55%的五价疫苗免疫猴免受猴免疫缺陷病毒（SHIV）的攻击。系统血清学分析抗体反应，确定了针对感染 HIV 的细胞的血浆抗体结合、峰值 ADCC 抗体滴度、NK 细胞介导的 ADCC 和 NK 细胞中 MIP-1β的抗体介导激活，这四个免疫参数可最好地预测感染风险降低，并且五价疫苗可改善这些参数。因此，在痘苗病毒初免/蛋白加强方案中加入额外的 gp120 免疫原可以增强抗体反应，并增强恒河猴对 SHIV 攻击的保护作用。