Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial.
Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial.
复制标题
DOI：
10.7326/m15-0880
复制
发表时间：
2016-03-01
影响因子：
39.2
通讯作者：
B003-IPCAVD004-HVTN091 Study Group
中科院分区：
文献类型：
--
作者：
Baden LR;Karita E;Mutua G;Bekker LG;Gray G;Page-Shipp L;Walsh SR;Nyombayire J;Anzala O;Roux S;Laher F;Innes C;Seaman MS;Cohen YZ;Peter L;Frahm N;McElrath MJ;Hayes P;Swann E;Grunenberg N;Grazia-Pau M;Weijtens M;Sadoff J;Dally L;Lombardo A;Gilmour J;Cox J;Dolin R;Fast P;Barouch DH;Laufer DS;B003-IPCAVD004-HVTN091 Study Group
预防性HIV-1疫苗是全球卫生优先事项。评估一种新型疫苗平台作为预防性HIV-1疫苗方案。这项随机、双盲、安慰剂对照试验在三个地理区域（美国、东非和南非）评估了两种候选HIV-1疫苗（Ad26.EnvA和Ad35-Env，均为5 × 1010 vp）的同源和异源组合。受试者和研究人员均对治疗分配设盲。(NCT 01215149）。健康的未感染艾滋病毒的成年人。评估了安全性和免疫原性，并分析了基线载体免疫的影响。217例受试者接受了至少1次疫苗接种，210例（> 96%）完成随访，未发生疫苗相关严重不良事件。尽管与安慰剂接受者（20.5%）相比，更多的疫苗接受者（36.5%）出现一过性中度或重度全身反应，但所有方案通常耐受良好。所有方案引起体液和细胞免疫反应，几乎所有的志愿者。预先存在的Ad26或Ad35中和抗体滴度对疫苗安全性没有影响，对免疫原性几乎没有影响。在同源和异源方案中，第二次接种显著增加EnvA抗体滴度（从30 - 300至3000的中值ELISA滴度约20倍）。异源方案Ad26-Ad35引起比Ad35-Ad26显著更高的EnvA抗体滴度。东非的T细胞反应较低，低于南非和美国。两种疫苗在所有人群中都引起了显著的免疫应答。基线载体免疫对免疫应答没有显著影响。所有方案中的第二次疫苗接种显著提高了EnvA滴度，尽管异源方案中的疫苗顺序对免疫应答具有适度的影响。IAVI、NIAID/NIH和Ragon研究所与Crucell Holland BV合作。
A prophylactic HIV-1 vaccine is a global health priority. To assess a novel vaccine platform as a prophylactic HIV-1 vaccine regimen. This randomized, double-blind, placebo-controlled trial assessed two candidate HIV-1 vaccines (Ad26.EnvA and Ad35-Env both at 5×1010 vp) in homologous and heterologous combinations in three geographic regions (US, East and South Africa). Both subjects and study personnel were blinded to treatment allocation. (NCT 01215149). Healthy HIV uninfected adults. Safety and immunogenicity were assessed and the impact of baseline vector immunity was analyzed. 217 subjects received at least 1 vaccination and 210 (>96%) completed follow-up, No vaccine-associated serious adverse events occurred. All regimens were generally well tolerated though more vaccine recipients had transient moderate or severe systemic reactions (36.5%) compared to placebo recipients (20.5%). All regimens elicited humoral and cellular immune responses in nearly all volunteers. There was no impact of pre-existing Ad26 or Ad35 neutralizing antibody titers on vaccine safety and little on immunogenicity. In both homologous and heterologous regimens the second vaccination significantly increased EnvA antibody titers (~20 fold from median ELISA titers of 30–300 to 3000). The heterologous regimen Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T cell responses were modest and lower in East Africa than in South Africa and the United States. Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not have a significant impact on immune responses. Second vaccinations in all regimens significantly boosted EnvA titers though vaccine order in the heterologous regimen had a modest effect on the immune response. IAVI, NIAID/NIH, and the Ragon Institute in collaboration with Crucell Holland BV.