{"id":2806,"date":"2015-02-20T10:17:11","date_gmt":"2015-02-20T10:17:11","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=2806"},"modified":"2015-02-20T10:17:11","modified_gmt":"2015-02-20T10:17:11","slug":"the-journey-to-an-hiv-vaccine-endures","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/the-journey-to-an-hiv-vaccine-endures\/","title":{"rendered":"The Journey to an HIV Vaccine Endures"},"content":{"rendered":"

\"shutterstock_174737015\"<\/a>HIV virus possesses inherently complicated nature due to which despite of more than 30 years of efforts,\u00a0scientists have not yet come up with a reliably effective HIV vaccine.<\/span><\/p>\n

There are nine HIV subtypes (called \u201cclades\u201d) in different global populations, according to the World Health Organization. Once the virus enters the body, it can mutate so frequently that it evades the body\u2019s immune response.<\/span><\/p>\n

\u201cOne reason why it\u2019s been so difficult to make an HIV vaccine is that the virus infects the very immune cells that the vaccine should induce,\u201d Guido Silvestri, M.D., chief of microbiology and immunology at Yerkes National Primate Research Center of Emory University in Atlanta, GA, toldDrug Discovery & Development<\/em>.<\/span><\/p>\n

HIV invades the body by destroying the immune system\u2019s CD-4 cells, which are necessary to generate antibodies against the virus. The virus mutates and hides in CD-4 cell reservoirs. When these cells multiply to fight an infection, they end up making more copies of the virus.<\/span><\/p>\n

Scientists are gaining insight into the biology of HIV: they\u2019ve identified certain areas of the virus that don\u2019t change as continuously, making them prime targets for attack by antibodies.<\/span><\/p>\n

The first trial with successful results<\/strong><\/span><\/p>\n

\n

\"Glenda<\/a>
Glenda Gray, MBBCH, president of the South African Medical Research Council<\/figcaption><\/figure>\n

This was the case with the 2009 clinical trial in Thailand. The trial, which included more than 16,000 volunteers, was the largest clinical trial ever conducted for an HIV vaccine \u2014 and also the first to show protection against infection.<\/span><\/p>\n

Two previously developed vaccines, ALVAC-HIV and AIDSVAX, were used in conjunction, with the first initiating an immune response and the second acting as an immunity<\/span><\/p>\n

booster. The combination, vaccine RV144, reduced HIV risk by a modest 31.2 percent at the end of the three-year study. (Although the vaccine peaked early\u2014it was 60 percent effective at the one-year mark\u2014its effect quickly declined.) Prior to these results, it wasn\u2019t known if a vaccine was achievable.<\/span><\/p>\n

\u201cMy colleagues and I were incredibly excited, almost disbelieving, since the vaccines had not worked by themselves,\u201d Glenda Gray, MBBCH, president of the South African Medical Research Council, told\u00a0Drug Discovery & Development<\/em>. Gray, who is based in Johannesburg, directs the Africa Programs for the\u00a0HIV Vaccine Trials Network<\/span><\/a>\u00a0(HVTN), the largest worldwide clinical trials network dedicated to the development and testing of HIV\/AIDS vaccines. \u201cSoon after, we convened to discuss how we could translate the findings into other parts of the world.\u201d<\/span><\/p>\n

A promising HIV vaccine in South Africa<\/strong><\/span><\/p>\n

South Africa has the world\u2019s highest HIV\/AIDS statistic, with an estimated 6.3 million people living with HIV\/AIDS. (An estimated 35 million people live with HIV globally.) New infections, called seroconversions, increase at about 370,000 per year in the region\u2014about 1,000 new infections every day.<\/span><\/p>\n

The first in a series of trials designed to build on the success of the Thailand vaccine passed the test: a safety trial using the same vaccine regimen from RV144\u2014but with an added booster shot 12 months afterward, which produced immune responses\u2014triggered the production of CD-4 cells\u2014in healthy adults who received the vaccination. \u201cThe durability of the Thai HIV vaccine regimen was not maintained,\u201d Gray told\u00a0Drug Discovery & Development<\/em>, \u201cso the idea was to add a more potent adjuvant to the protein part of the regimen, and boost again at 12 months to increase the potency and durability of the regimen.\u201d An ideal HIV vaccine would provide lifelong protection, or at least for a decade.<\/span><\/p>\n

Sixty-eight of the 100 participants had responses \u201ccomparable to or better than those induced in RV144.\u201d The results were presented in late October at the HIV Research for Prevention 2014 conference.<\/span><\/p>\n

In early 2015,\u00a0clinical trials<\/span><\/a>\u00a0began of a modified vaccine tailored to South Africa. An efficacy trial will enroll about 7,000 participants, and results are expected in 2018.<\/span><\/p>\n

\u201cSouth Africa has a clade C epidemic, so the first thing we needed to do was make the products clade C specific,\u201d Gray told\u00a0Drug Discovery & Development<\/em>. The subtype \u201cC\u201d in South Africa is different than subtypes \u201cB\u201d and \u201cE\u201d found in Thailand. \u201cNow, we are taking the optimized regimen that is clade C-specific with a new protein and adjuvant and are testing this regimen to evaluate whether we can go ahead and do a Phase 3 trial that will lead to licensure.\u201d<\/span><\/p>\n

How many years might an HIV vaccine take to develop? \u201cIt\u2019s an iterative process,\u201d Gray told\u00a0Drug Discovery & Development<\/em>. \u201cWe don\u2019t know what we don\u2019t know. So we need to take baby steps and learn from trials, and improve the regimen each time.\u201d<\/span><\/p>\n

Broadly neutralizing antibodies<\/strong><\/span><\/p>\n

\"HIV<\/a>
1. viral envelop; 2. matrix; 3. capsid; 4.gp120 glycoprotein; 5. integrase; 6. viral RNA; 7. reverse transcriptase; 8. glycan shield; 9. v1-v2 loop; 10. v3 loop; 11. CD4 binding site; 12. MPER (credit: HVTN)<\/figcaption><\/figure>\n

Antibodies that adhere to the outer envelope, or protein coat, of HIV can inactivate the virus, and potentially stop infection before it begins. An ideal vaccine would produce antibodies that activate all HIV strains. But antibodies against one strain usually don\u2019t work against others.<\/span><\/p>\n

In a\u00a0breakthrough<\/span><\/a>\u00a0for HIV vaccines, researchers found that some\u00a0HIV-infected people naturally produce antibodies<\/span><\/a>\u00a0that are effective in working against many different HIV strains. These antibodies are called broadly neutralizing antibodies (bnAbs). A problem, though, is that these bnAbs form too late, when people are already infected.<\/span><\/p>\n

However, since bnAbs can be isolated, scientists can learn about their structure and targets. \u201cThis is all very good news,\u201d Silvestri told\u00a0Drug Discovery & Development<\/em>. \u201cNot enough, of course, but a good solid scientific foundation to build on.\u201d The goal: todevelop future vaccines<\/span><\/a>\u00a0that can generate bnAbs before HIV exposure to block HIV infection.<\/span><\/p>\n

HVTN 104, a\u00a0Phase 1<\/span><\/a>\u00a0clinical trial, will examine the safety and potential of administering bnAbs via injections, and set the stage for subsequent studies. Next up, would be human trials that show that a vaccine can elicit broadly neutralizing antibodies, particularly antibodies that could be maintained for a long period of time.<\/span><\/p>\n

A different approach<\/strong><\/span><\/p>\n

Most recently, scientists at the Scripps Research Institute in Florida found a\u00a0new method to blocking HIV<\/span><\/a>\u2014with a compound described by Michael Farzan, Ph.D., infectious disease specialist at the institute, as \u201ca potent entry inhibitor\u201d against the virus. The technique worked in non-human primates. The next step, Farzan said, will be to test the compound in infected non-human primates and later, to potentially begin human trials.<\/span><\/p>\n

\n","protected":false},"excerpt":{"rendered":"

HIV virus possesses inherently complicated nature due to which despite of more than 30 years of efforts,\u00a0scientists have not yet come up with a reliably effective HIV vaccine. There are nine HIV subtypes (called \u201cclades\u201d) in different global populations, according to the World Health Organization. Once the virus enters the body, it can mutate so […]<\/p>\n","protected":false},"author":6,"featured_media":2807,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[],"class_list":["post-2806","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015-150x150.jpg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015-300x300.jpg",300,300,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",490,490,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",360,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",65,65,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",500,500,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",96,96,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/02\/shutterstock_174737015.jpg",150,150,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Medicine<\/a>","tag_info":"Medicine","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/2806","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=2806"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/2806\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/2807"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=2806"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=2806"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=2806"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}