Baden Lindsey R, Karita Etienne, Mutua Gaudensia, Bekker Linda-Gail, Gray Glenda, Page-Shipp Liesl, Walsh Stephen R, Nyombayire Julien, Anzala Omu, Roux Surita, Laher Fatima, Innes Craig, Seaman Michael S, Cohen Yehuda Z, Peter Lauren, Frahm Nicole, McElrath M Juliana, Hayes Peter, Swann Edith, Grunenberg Nicole, Grazia-Pau Maria, Weijtens Mo, Sadoff Jerry, Dally Len, Lombardo Angela, Gilmour Jill, Cox Josephine, Dolin Raphael, Fast Patricia, Barouch Dan H, Laufer Dagna S
Ann Intern Med. 2016 Mar 1;164(5):313-22. doi: 10.7326/M15-0880. Epub 2016 Feb 2.
A prophylactic HIV-1 vaccine is a global health priority.
To assess a novel vaccine platform as a prophylactic HIV-1 regimen.
Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149).
United States, East Africa, and South Africa.
Healthy adults without HIV infection.
2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.
Safety and immunogenicity and the effect of baseline vector immunity.
217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of 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.
Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.
Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.
International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.
预防性HIV-1疫苗是全球卫生重点。
评估一种新型疫苗平台作为预防性HIV-1方案。
随机、双盲、安慰剂对照试验。参与者和研究人员均对治疗分配不知情。（ClinicalTrials.gov：NCT01215149）。
美国、东非和南非。
未感染HIV的健康成年人。
两种HIV-1疫苗（携带HIV-1包膜A插入片段的26型腺病毒[Ad26.EnvA]和携带HIV-1包膜A插入片段的35型腺病毒[Ad35.Env]，均以5×10¹⁰病毒颗粒的剂量给药），采用同源和异源组合。
安全性、免疫原性以及基线载体免疫的影响。
217名参与者接受了至少1次疫苗接种，210名（>96%）完成了随访。未发生与疫苗相关的严重不良事件。所有方案总体耐受性良好。所有方案在几乎所有参与者中均引发了体液和细胞免疫反应。预先存在的Ad26或Ad35中和抗体滴度对疫苗安全性无影响，对免疫原性影响较小。在同源和异源方案中，第二次接种均显著提高了EnvA抗体滴度（从中位酶联免疫吸附测定滴度30 - 300提高到3000，约20倍）。Ad26 - Ad35的异源方案比Ad35 - Ad26引发的EnvA抗体滴度显著更高。T细胞反应较弱，且在东非低于南非和美国。
由于两种包膜插入片段不相同，加强反应难以解释。1年以上引发的免疫反应的持久性未知。
两种疫苗在所有人群中均引发了显著的免疫反应。基线载体免疫未显著影响反应。所有方案中的第二次接种均显著提高了EnvA抗体滴度，尽管异源方案中的疫苗接种顺序对免疫反应有适度影响。
国际艾滋病疫苗倡议组织、美国国立卫生研究院、拉贡研究所、荷兰Crucell公司。
