Science: large scale clinical trials show that HIV vaccine primary immunization enhanced immunization strategy fails

February 6, 2020 / Biogen / - -- another frustrating failure in the search for a vaccine that can stop HIV One of the fastest-growing HIV vaccines in human testing has failed, and a $104 million clinical trial to evaluate the vaccine in South Africa has been terminated prematurely "There is absolutely no evidence that it works," said Glenda gray, head of the clinical trial and President of the South African Medical Research Council This is the research work for many years It's so disappointing " This clinical efficacy study, known as HVTN 702, began in October 2016 It recruited 5407 sexually active, HIV free men and women aged 18 to 35 in 14 locations across South Africa The researchers randomly assigned half of the participants to receive two kinds of HIV vaccines with a combined fist strategy called prime boost, while the other half received a placebo The clinical trial should have lasted until July 2022 However, on January 23, 2020, an independent oversight committee that reviewed the data as planned to assess safety and effectiveness informed gray and the other leaders of the clinical study that it would be futile to continue There were 129 infections in the vaccination group and 123 in the placebo group Image source: NIAID There is no evidence that the vaccine can cause harm, as in another large HIV vaccine study that abruptly ended in 2007 Susan Buchbinder, an epidemiologist at the University of California, San Francisco, who co chaired the thought-provoking study, congratulated her colleagues in South Africa on a rigorous and complex clinical trial "This clinical trial is very well done, and we have a clear answer, which is the significance of science," Buchbinder said Buchbinder is the head of a multinational clinical trial called mosaico Mosaico research is the most advanced large-scale HIV vaccine research in progress In this terminated HVTN 702 clinical trial, the vaccine for "prime" is a harmless Canary pox virus carrying one surface protein of HIV and two other structural proteins The vaccine for boost contains a recombinant form of the HIV surface protein and an immune system booster, the adjuvant MF59 Many HIV scientists doubt the success of this clinical study in South Africa, because in a efficacy study in Thailand (hereinafter referred to as the Thai clinical trial), the vaccine used in the primary enhanced immunization program only produced poor results In Thailand clinical trials that ended in 2009, there were 51 HIV cases in the vaccine group and 74 HIV cases in the placebo group, with a therapeutic efficiency of 31% It is generally agreed that bringing the vaccine to market is not enough to provide adequate protection, but scientists disagree on whether it makes sense to try to optimize or abandon the vaccine Gray said that in view of the severity of the HIV epidemic in South Africa (7.7 million of the 37.9 million people living with HIV in the world), she and her colleagues have slightly improved the vaccine used in the Thai clinical trial and believe that the new clinical trial is worth trying Gray said: "the HIV epidemic is out of control here, and we have to take measures for biomedical intervention." Anthony Fauci, director of the National Institute of allergy and infectious diseases, said he has no regrets about funding the study "I don't think it's a bad choice This is the only option " So far, no one knows which immune response can prevent HIV infection, that is, the so-called correlation of immunity But many researchers have been working on developing a vaccine to trigger the production of antibodies that neutralize HIV's ability to infect cells in laboratory research Fauci points out that vaccines used in clinical trials in Thailand trigger the production of antibodies that bind to HIV, but they cannot neutralize the virus, increasing the possibility that the vaccines used are sufficient to provide some protection "We've been fighting for years, so it seems interesting that we've caught the slightest positive impact, a potential immune related factor," he said Given the severity of the epidemic, if that's all we have, and vaccines that stimulate neutralizing antibody production don't appear for years, what would you do or nothing? " Fauci points out that Thailand's clinical trials involve people with a relatively low risk of infection (the annual rate of new infections is about 0.3%), which means that if the immune response generated by the primary enhanced immunization strategy does not face repeated HIV attacks, it may work In clinical studies in South Africa, the annual rate of new infections is about 4% for women and 1% for men "The immune protection it provides is completely suppressed," Fauci said Mitchell Warren, head of avac, a nonprofit HIV prevention advocacy group, said the latest failure would not slow down the development of the vaccine sector Warren is also a member of the oversight committee that recommends stopping clinical trials in South Africa "There are other products that are being tested for clinical efficacy, and one product line in the phase 1 trial is slightly larger than what we have had for a long time," he said The candidate vaccine being tested in mosaico clinical trials, made by Janssen vaccines, is now in the lead Its primary and enhanced immunization program began with a preparation containing a genetic chimera of different HIV subtypes The chimera is carried by a harmless adenovirus In earlier tests, the vaccine also failed to trigger neutralizing antibody production, but produced high levels of binding antibodies and other immune responses The vaccine used to enhance immunity consists of HIV surface protein chimeric version and alum adjuvant This primary and intensive immunization strategy worked well in monkeys who were vaccinated and then "attacked" them with simian immunodeficiency virus (SIV) In the mosaico clinical trial, transgenders and men who have sex with men in North America and Europe will be vaccinated The vaccine is also being tested in a smaller sister study of women in sub Saharan Africa called imbokodo Imboko's results are expected to be published next year, while mosaico's will be published in 2023 (Bio Valley Com) reference: Jon Cohen Another HIV vaccine strategy failures in large-scale study Science, 2020, DOI: 10.1126/science.abb1480