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Barouch博士说：“APPROACH研究之有潜力的早期研究结果支持对该候选疫苗进一步评估其保护HIV风险人群的效果。” Barouch博士是APPROACH研究的PI（主要研究者），也是Beth Israel Deaconess在波士顿的药物研究中心的病毒学和疫苗学中心的主任，同时也是哈佛医学院的医学教授。
在接种第三次疫苗之后，大多数APPROACH的受试者均已经产生了抗体，对HIV病毒产生了细胞免疫应答。接种不同的增强疫苗产生具有不同程度和特征的免疫应答，在猴子上显示出最大保护作用的免疫应答的方案在人体内也产生了最大的免疫应答。在接种了第四次疫苗之后，抗HIV免疫应答继续增强。
研究人员得出结论，该研究的进一步评估将会使用的试验方案包含两个Ad26嵌合初始疫苗和两个增强疫苗，该增强疫苗由Ad26嵌合和clade C gp140组成。正在进行的TRAVERSE试验比较三价（以Ad26为基础，包含3个嵌合抗原片段）和四价（以Ad26为基础，包含4个嵌合抗原）两个试验方案的效果。该试验的结果预计在2017年年底获得。
支持APPROACH试验的还有：美国军方艾滋病毒研究计划、国际艾滋病疫苗促进会、Beth Israel Deaconess药物研究中心、麻省总院的拉根研究所、麻省理工学院和哈佛大学。关于APPROACH研究的相关信息，可通过ClinicalTrials.gov检索登记号为 NCT02315703的临床试验，关于TRAVERSE的更多信息，可检索ClinicalTrials.gov检索登记号为 NCT02788045。
以下是英文原文：
Experimental HIV vaccine regimenis well-tolerated, elicits immune responses
Results fromearly-stage NIH-funded trial support further development of candidate vaccines.
Results from an early-stage clinical trial called APPROACH showthat an investigational HIV vaccine regimen was well-tolerated and generatedimmune responses against HIV in healthy adults. The APPROACH findings, as wellas results expected in late 2017 from another early-stage clinical trial calledTRAVERSE, will form the basis of the decision whether to move forward with alarger trial in southern Africa to evaluate vaccine safety and efficacy amongwomen at risk of acquiring HIV.
The APPROACH results will be presented July 24 at the 9thInternational AIDS Society Conference on HIV Science in Paris.
The experimental vaccine regimens evaluated in APPROACH arebased on “mosaic” vaccines designed to induce immunological responses against awide variety of HIV subtypes responsible for HIV infections globally. DifferentHIV subtypes, or clades, predominate in various geographic regions around theworld. The National Institute of Allergy and Infectious Diseases (NIAID), partof the National Institutes of Health, funded pre-clinical development of thesevaccines. Together with other partners, NIAID supported the APPROACH trial,which is sponsored by Janssen Vaccines & Prevention B.V., part of theJanssen Pharmaceutical Companies of Johnson & Johnson. The manufacture andclinical development of the mosaic vaccines are led by Janssen.
“A safe and effective HIV vaccine would be a powerful tool toreduce new HIV infections worldwide and help bring about a durable end to theHIV/AIDS pandemic,” said NIAID Director Anthony S. Fauci, M.D. “By exploringmultiple promising avenues of vaccine development research, we expand ouropportunities to achieve these goals.”
APPROACH involved nearly 400 volunteers in the United States,Rwanda, Uganda, South Africa and Thailand who were randomly assigned to receiveone of seven experimental vaccine regimens or a placebo. APPROACH found thatdifferent mosaic vaccine regimens were well-tolerated and capable of generatinganti-HIV immune responses in healthy, HIV-negative adults. Notably, the vaccineregimen that was most protective in pre-clinical studies in animals elicitedamong the greatest immune responses in the study participants. However, furtherresearch will be needed because the ability to elicit anti-HIV immune responsesdoes not necessarily indicate that a candidate vaccine regimen can prevent HIVacquisition.
According to the researchers, the findings from APPROACH, aswell as from animal studies, support further evaluation of a lead candidateregimen in a clinical trial to assess its safety and efficacy. Plans for such aclinical trial to be conducted in southern Africa are in development, withprojected enrollment of 2,600 healthy, HIV-negative women. Should the largertrial move forward, it is expected to begin enrollment in late 2017 or early2018.
In APPROACH, study participants received four vaccinations over48 weeks: two doses of an initial, or “prime,” vaccine, followed by two dosesof a booster vaccine. The experimental regimens all incorporated the samevaccine components in the prime vaccination, known as Ad26.Mos.HIV. The vaccineuses a strain of common-cold virus (adenovirus serotype 26, or Ad26),engineered so that it does not cause illness, as a vector to deliver threemosaic antigens created from genes from many HIV variants. The boostervaccination included various combinations of the Ad26.Mos.HIV components or adifferent mosaic component, called MVA-Mosaic, and/or two different doses ofclade C HIV gp140 envelope protein containing an aluminum adjuvant to boostimmune responses.
The Ad26-based mosaic vaccines were initially developed by thelaboratory of NIAID grantee Dan H. Barouch, M.D., Ph.D., and Janssen. Inpre-clinical studies, regimens incorporating these mosaic vaccines protectedmonkeys against infection with an HIV-like virus called simian humanimmunodeficiency virus (SHIV). The most effective prime-boost regimen reducedthe risk of infection per exposure to SHIV by 94 percent and resulted in 66percent complete protection after six exposures. Researchers identified and characterizedthe vaccine-induced immune responses that correlated with this protection.
