幸好HIV的投入大，只是挫折到目前为止太多了一点。
只能说，我们对于HIV疫苗的追求太执着了。
先简单介绍一下这项实验：
2016年，HVTN 702在南非开始。是RV144的后继实验，因为在南非进行现场实验，所以把针对的毒株换成了南非最流行的C亚型。
试验招募了5407名HIV阴性的受试者。都是性活动活跃的两性，年龄在18~35岁，随机分组，分别接受实验性疫苗或者安慰剂对照。总共是在18个月时间范围内打6针。受试者也都告知了该知道的预防HIV感染的须知，包括暴露前预防用药。
2020.1.23进行中期分析的时候——
结果里相差几例是没有统计学差异的，但是也说明疫苗没什么保护作用。研究单位也放弃对后续受试者的追踪。
这次HVTN 702临床实验使用的疫苗是HIV金丝雀痘病毒载体疫苗（ALVAC-HIV）和两组分gp120蛋白的亚单位疫苗的组合疫苗，佐剂使用的葛兰素史克（GSK）的专利佐剂MF59，这个佐剂与前置试验RV144用的不一样。
HIV金丝雀痘病毒载体疫苗（ALVAC-HIV）是赛诺菲巴斯德（ Sanofi Pasteur）的产品。gp120亚单位疫苗是GSK的。
目前研究单位还在系统分析数据，后续将发表相关报告。
资助方NIH有还有多项开展的预防HIV的研究（金主们不要放弃），包括：两项多中心的、靠后期的Imbokodo和Mosaico。并且使用的疫苗和这次失败的HVTN 702使用的不一样。
此外，原理验证的研究，比如通过静脉注射试验性抗体来预防HIV感染。比如目前正在试验的广谱中和抗体是否能预防HIV感染。另外两个大型临床试验正在验证注射长效的抗逆转录药物（cabotegravir/GSK-1265744，一个月打一针就行了）。另外还有其他概念的预防HIV策略，比如联用多种广谱中和性抗体、阴道环等等。
我倒是觉得长效逆转录抑制剂概念挺好，疫苗实在是太困难了。还不如针对这种突变率相对低一点的靶点。
另外就是广谱中和抗体，这种抗体能够产生，但是大部分是祖B细胞产生的，成熟的B细胞会把这些抗体“优化”掉。但是如果能够突破抗原设计，专门诱导产生广谱中和抗体的B细胞，那疫苗还是有一定希望的。
不过预防HIV，最重要的是洁身自好，风险行为前一定要做好防护措施。
想初尝禁果的小朋友们，提前了解一下相关知识比较好，不要事后追悔莫及。
原文重点信息——
The Phase 2b/3 study, named HVTN 702 or Uhambo, began in 2016 and is taking place in South Africa. It was testing an investigational prime-boost vaccine regimen based on the only vaccine regimen ever to show protection from HIV—the regimen tested in the RV144 clinical trial in Thailand led by the U.S. Military HIV Research Program and the Thai Ministry of Health. For HVTN 702, the vaccine regimen was adapted to the HIV subtype Clade C most common in southern Africa, where the pandemic is most pervasive.
“An HIV vaccine is essential to end the global pandemic, and we hoped this vaccine candidate would work. Regrettably, it does not,” said NIAID Director Anthony S. Fauci, M.D. “Research continues on other approaches to a safe and effective HIV vaccine, which I still believe can be achieved.”
The HVTN 702 study enrolled 5,407 HIV-negative volunteers at 14 sites across South Africa. The study population consisted of sexually active men and women aged 18 to 35 years. The study volunteers were randomly assigned to receive either the investigational vaccine regimen or placebo injections. Study participants received six injections over 18 months. As with all NIAID-sponsored HIV prevention trials, the safety of HVTN 702 study participants was closely monitored throughout the trial, and participants were offered the local standard of care for preventing HIV, including access to oral pre-exposure prophylaxis (PrEP).
In the January 23, 2020 interim analysis, the DSMB examined data from 2,694 volunteers who received the investigational vaccine regimen and 2,689 volunteers who received the placebo injection. The analysis looked at how many participants were diagnosed with HIV after at least 60% of the participants had been in the study for more than 18 months — enough time for the vaccine regimen to stimulate an immune response. In this analysis, 129 HIV infections occurred among the vaccine recipients, and 123 HIV infections occurred among the placebo recipients.
Based on these findings, the DSMB concluded that the investigational vaccines had not shown any efficacy. The DSMB recommended that no further vaccinations be administered and that participants remain in the study for follow-up. The report noted there was no significant evidence of either decreased or increased infection rates with vaccination.
NIH is investing in multiple approaches to prevent HIV with the goal of delivering new options that are safe, effective, desirable to diverse populations, and scalable worldwide to help end the global pandemic. These efforts include two other late-stage, multinational vaccine trials, Imbokodo and Mosaico, both testing a novel mosaic vaccine regimen and being sponsored by Janssen Vaccines & Prevention, B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson. The vaccine concept being tested in these trials is different than the one under investigation in HVTN 702.
In addition, the proof-of-concept AMP trials are testing an intravenously delivered investigational antibody for preventing HIV. Other cutting-edge studies, including the AMP trials, are investigating if broadly neutralizing antibodies (bNAbs) can protect against HIV. Twoother large-scale trials are testing an investigational long-acting injectable antiretroviral drug, cabotegravir, for HIV prevention. Additional novel, long-acting HIV prevention products are also under study, including implants, vaginal rings, combinations of bNAbs, and multi-purpose products that offer contraception along with HIV prevention.
The HVTN 702 vaccine regimen consisted of two experimental vaccines: a canarypox vector-based vaccine called ALVAC-HIV and a two-component gp120 protein subunit vaccine with an adjuvant to enhance the body’s immune response to the vaccine. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein vaccine (supplied by GSK) were modified from the versions used in RV144 to be specific to HIV subtype C. Additionally, the protein subunit vaccine in HVTN 702 was combined with MF59, a different adjuvant than the one used in RV144, in the hope of generating a more robust and durable immune response. Finally, the HVTN 702 vaccine regimen included booster shots at the one-year and 18-month timepoints in an effort to prolong the early protective effect observed in RV144. HVTN 100, a predecessor clinical trial using the HVTN 702 regimen, found that the new vaccine regimen was safe and induced high and boostable titers of antibodies to several HIV strains prevalent in southern Africa.
NIAID and the HVTN 702 study team are working to thoroughly analyze the study data to guide future vaccine development efforts. Detailed scientific findings will be made public as soon as possible. For more information about the HVTN 702 study, please seethe updated Questions and Answers. Learn more aboutNIAID’s HIV vaccine research.
Experimental HIV vaccine regimen ineffective in preventing HIV
