关于HIV疫苗，美国官方机构NIH又是如何报道的呢？

最近几天，关于上图报道的HIV预防性疫苗试验结果的解读文章占据了我们的手机屏幕，观点各不相同，可以说是大相径庭。下面是两个例子。

那么，美国官方机构NIH又是如何报道的呢？

美国国立卫生研究院（(National Institutes of Health，简称NIH）位于美国马里兰州贝塞斯达（Bethesda），是美国最高水平的医学与行为学研究机构，初创于1887年，任务是探索生命本质和行为学方面的基础知识，并充分运用这些知识延长人类寿命，以及预防、诊断和治疗各种疾病和残障。NIH在近几十年取得的研究成果极大地改善了人类的生命健康状况。

药时代翻译志愿者联盟的朋友们翻译了NIH于2017年7月24日发布的新闻稿，题为《Experimental HIV vaccine regimen is well-tolerated, elicits immune responses》（试验性HIV疫苗试验方案具有良好的耐受性，引发免疫应答）的文章。现在与朋友们分享这篇译文。文末还附上新闻稿的英文原文和强生公司于2017年7月24日发布的新闻稿原文，供感兴趣的朋友惠阅。欢迎朋友们对译文进行批评指正！

试验性HIV疫苗试验方案具有良好的耐受性，引发免疫应答

NIH资助的早期临床试验的结果支持在研疫苗的进一步开发

一项名为APPROACH的早期临床试验的结果表明，研究性HIV疫苗试验方案在健康成年人中具有良好的耐受性并产生针对艾滋病毒的免疫应答。APPROACH研究结果，以及预计在2017年晚些时候从另一个名为TRAVERSE的早期临床试验中获得的结果，将成为决定是否在南部非洲进行更大规模试验的基础，这些更大规模试验旨在评估疫苗对具有感染艾滋病毒风险的女性的安全性和有效性。

APPROACH研究结果将于7月24日在巴黎举办的国际艾滋病协会聚焦HIV科学的第九届学术会议上公布。

APPROACH试验评估的试验疫苗方案是基于“马赛克”疫苗，该疫苗引发针对造成全球范围内艾滋病毒感染的各种艾滋病毒亚型的免疫反应。不同的艾滋病毒亚型或分支在世界不同的区域占主导地位。美国国家过敏和传染病研究所（NIAID）是美国国家卫生研究院的一部分，资助了这些疫苗的临床前开发。之后，NIAID又与其他合作伙伴一起支持由强生制药公司旗下的Janssen Vaccines＆Prevention B.V.发起的APPROACH人体临床试验。马赛克疫苗的制造和临床开发由杨森领导。

NIAID总监AnthonyS. Fauci博士说：“安全有效的艾滋病毒疫苗将成为全球减少新的艾滋病毒感染并有助于持续结束艾滋病毒/艾滋病流行病的强大手段。” 通过探索多种潜在的疫苗开发研究途径，增加实现这些目标的机会。”

APPROACH试验将400名来自美国、卢旺达、乌干达、南非以及泰国的健康志愿者随机分组，分别接受7个试验疫苗治疗方案中的一个或安慰剂。研究发现HIV病毒阴性的健康志愿者对不同的疫苗均有很好的耐受性且可以产生抗HIV的免疫反应。非常明显的是，在临床前的动物试验中保护作用最强的疫苗能够在人体上产生最强大的免疫反应。然而，此疫苗能够产生抗HIV免疫反应不能代表候选疫苗预防HIV病毒，仍需开展后续的研究。

研究者表示，APPROCH试验和动物研究的结果支持在临床试验中进一步评估最有希望的候选疫苗的安全性和有效性。此项临床试验的计划正在南非制定，计划招募2600位HIV阴性的女性健康志愿者。一旦该大型试验向前推进，预计2017年末或者2018年初将会开始招募。

在APPROACH试验中，参与者在48周内接受4次疫苗接种：两次起始剂量，或称为初免疫苗，再继续接受两个剂量的增强疫苗。初次接种的试验疫苗均包含同种疫苗成分，即Ad26.Mos.HIV。这种疫苗使用了一株经过改变而不会产生疾病的感冒病毒（腺病毒血清型26，或Ad26）作为载体，传递三种产生于多种HIV变异体基因的嵌合抗原。增强疫苗包括多种组合，其中有Ad26.Mos.HIV成份或称为MVA-Mosaic的不同的嵌合抗原成份，和/或两个不同剂量的包含铝佐剂的clade C HIV gp140包膜蛋白，以加强免疫反应。

以Ad-26为基础的嵌合疫苗最初是由获得NIAID基金的Dan H. Barouch, M.D., Ph.D.的实验室和杨森开发。在临床前试验中，使用这些嵌合疫苗的试验方案使得猴子免于遭受一种类似于HIV病毒的猿猴人类免疫缺陷病毒（SHIV）的感染。最有效的初免-增强方案能够将单次接触SHIV时的感染风险降低94%，并且在6次接触后66%的猴子没有感染该病毒。研究者鉴定并表征了与保护作用相关的疫苗引起的免疫反应。

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.

“The promising, early-stage results from the APPROACH studysupport further evaluation of these candidate vaccines to assess their abilityto protect those at risk of acquiring HIV,” said Dr. Barouch, a principalinvestigator for APPROACH. He also is director of the Center for Virologyand Vaccine Research at Beth Israel Deaconess Medical Center in Boston andprofessor of medicine at Harvard Medical School.

Following the third vaccination, most APPROACH participants haddeveloped antibody and cellular immune responses against HIV. The differentboost vaccines altered the magnitude and character of these immune responses,with the regimen that showed greatest protection in monkey studies alsoeliciting among the greatest immune responses in humans. The anti-HIV immuneresponses increased after the fourth vaccination.

The researchers conclude that further evaluation of thisapproach would use a regimen comprising two Ad26 mosaic primes and two boostswith Ad26 mosaic and clade C gp140. The ongoing TRAVERSE trial is comparingAd26-based regimens containing three mosaic antigens (trivalent) withAd26-based regimens containing four mosaic antigens (tetravalent). Results fromTRAVERSE are expected in late 2017.

Other support for APPROACH comes from the NIAID-funded HIVVaccine Trials Network, the U.S. Military HIV Research Program, the InternationalAIDS Vaccine Initiative, Beth Israel Deaconess Medical Center and the RagonInstitute of MGH, MIT and Harvard. For more information about APPROACH, seeClinicalTrials.gov using identifier NCT02315703.For more information about TRAVERSE, see ClinicalTrials.gov using identifier NCT02788045.

NIAID conducts and supports research — at NIH, throughout theUnited States, and worldwide — to study the causes of infectious and immune-mediateddiseases, and to develop better means of preventing, diagnosing and treatingthese illnesses. News releases, fact sheets and other NIAID-related materialsare available on the NIAID website.

下面是强生公司于2017年7月24日发布的新闻稿原文。

Johnson & Johnson Announces Encouraging First-in-Human Clinical Data for Investigational HIV Preventive Vaccine

In Phase 1/2a APPROACH study, HIV-1 antibody response observed in all healthy volunteers

Mosaic-based vaccine regimen is designed to elicit an immune response against a wide variety of HIV subtypes prevalent worldwide

Positive clinical and preclinical results inform selection of lead mosaic HIV vaccine regimen for further evaluation in Phase 2b proof-of-concept study

Paris, France, 24 July 2017 – Johnson & Johnson today announced encouraging first-in-human clinical data for an investigational HIV-1 vaccine regimen in development at its Janssen Pharmaceutical Companies. In an oral presentation of the early stage Phase 1/2a APPROACH study at the 9th IAS Conference on HIV Science (IAS 2017), the “mosaic”-based vaccine regimen from Janssen Vaccines & Prevention B.V. (Janssen) appeared to be well-tolerated and elicited HIV-1 antibody responses in 100% of healthy volunteers (n=393).

“Finding a preventive vaccine has proven to be one of the biggest scientific challenges in the 35-year quest to end the HIV pandemic. A successful preventive vaccine for HIV will need to provide broad protection against a wide range of viral strains,” said Professor Dan Barouch, Harvard Medical School, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a key collaborator for APPROACH. “These promising, early-stage results suggest that these vaccines utilizing mosaic immunogens should be evaluated further for their potential ability to achieve this historic goal.”

Significant progress has been made in the global battle against HIV/AIDS, including the development of critical antiretroviral treatments and HIV prevention tools, yet the disease remains one of the greatest global health threats of our time. An estimated 37 million people are currently living with HIV-1 globally, and nearly 2 million people become newly infected each year. An effective HIV vaccine is elusive due to the unique properties of the virus – including its genetic diversity and ability to mutate rapidly.

Mosaic-based vaccines contain immunogens created using genes from different HIV subtypes responsible for HIV-1 infections worldwide. These immunogens are delivered through viral vectors, including Janssen’s AdVac® technology based on adenovirus serotype 26 (Ad26). The viral vectors are combined with other components such as soluble proteins to form mosaic-based prime-boost vaccine regimens that first prime and then boost the immune system, with the aim of producing stronger and longer-lasting immunity to HIV.

Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson said, “In recent years, a new optimism has emerged that we will find an effective HIV vaccine in our lifetime. The results from today’s study add to that belief and we look forward to advancing to the next stage of clinical development as quickly as possible.”

In pre-clinical studies, regimens incorporating mosaic vaccines demonstrated protection against infection with an HIV-like virus. The most effective prime-boost regimen in these studies reduced the per-exposure risk of infection by 94 percent and resulted in 66 percent complete protection after six exposures.

Based on immunologic responses observed in APPROACH, as well as protection observed in pre-clinical studies, a lead HIV-1 vaccine regimen comprising Janssen’s Ad26 mosaic candidate and the Clade C gp140 soluble protein has been selected as the basis for further evaluation in a potential Phase 2b proof-of-concept efficacy study. Should this study move forward, Janssen and its global partners anticipate initiating this investigation in southern African countries in late 2017 or early 2018.

About the APPROACH Study
APPROACH (HIV-V-A004/NCT02315703) is a multi-center, randomized, parallel-group, placebo-controlled, double-blind Phase 1/2a study in 393 healthy HIV-uninfected adults in the US, Rwanda, Uganda, South Africa and Thailand. It is evaluating the safety, tolerability and immunogenicity of various mosaic-based, prime-boost vaccine regimens for HIV-1. These vaccine regimens contain two prime doses of the mosaic viral vector Ad26.Mos.HIV and two boosts of either Ad26.Mos.HIV, MVA-Mosaic and/or different doses of the soluble protein Clade C gp140 adjuvanted with aluminum phosphate. Vaccination schedules have been completed for all study participants and 12-month follow-up after the 4th dose is underway.

Results presented at IAS 2017 suggest that all vaccine regimens appeared to be well-tolerated. Injection site pain, headache and fatigue were the most common reported adverse events. The primary analysis post 3rd vaccination showed that most active vaccine regimens elicited antibody responses in 100% of study participants. Antibody titers against autologous Clade C and heterologous cross-clade Env antigens increased in groups boosted with gp140 protein, irrespective of vector. After the 4th vaccination, humoral and cellular responses further increased.

The APPROACH study was sponsored by Janssen with support from partner organizations including Beth Israel Deaconess Medical Center (BIDMC); the United States Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research (WRAIR), with the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH); the Ragon Institute; the International AIDS Vaccine Initiative (IAVI); and the HIV Vaccine Trials Network (HVTN).

About Janssen’s HIV Preventive Vaccine
Janssen’s HIV-1 AdVac®-based vaccine regimen, along with the company’s investigational Ebola and inactivated polio vaccine candidates, utilize Janssen’s PER.C6® production cell line technology, which has the potential to reduce costs by increasing vaccine production at lower reactor volume.

Since 2005, Janssen Vaccines & Prevention B.V. has been participating in the NIH-supported Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program under grants AI066305, AI078526 and AI096040. Janssen’s HIV vaccine program has also received funding from the United States Military HIV Research Program and the Ragon Institute.

Please visit www.jnj.com/HIV for further details on the breadth of HIV science being presented by Johnson & Johnson companies and its partners.

About Johnson & Johnson
Caring for the world one person at a time inspires and unites the people of Johnson & Johnson. We embrace research and science – bringing innovative ideas, products and services to advance the health and well-being of people. Our approximately 126,400 employees at more than 230 Johnson & Johnson operating companies work with partners in health care to touch the lives of over a billion people every day, throughout the world.

About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at @JanssenGlobal.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995, regarding development of a potential preventive vaccine for HIV. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Vaccines & Prevention B.V. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2017, including under “Item 1A. Risk Factors,” its most recently filed Quarterly Report on Form 10-Q, including under the caption “Cautionary Note Regarding Forward-Looking Statements,” and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

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