Editing HIV vaccine development (section)

===Phase II===

''Preventive HIV vaccines''
* A recombinant Adenovirus-5 HIV vaccine (called V520) was tested in two Phase 2b studies, Phambili and STEP. On December 13, 2004, recruitment began for the [[STEP study]], a 3,000-participant [[Clinical trial#Phase II|phase II clinical trial]] of a novel HIV vaccine, at sites in North America, South America, the Caribbean and Australia.<ref>{{cite web |url=http://www.stepstudies.com/new/locations.shtml |title=STEP Study Locations |access-date=2008-11-04 |archive-url=https://web.archive.org/web/20080724081503/http://www.stepstudies.com/new/locations.shtml |archive-date=2008-07-24  }}</ref>  The trial was co-funded by the [[National Institute of Allergy and Infectious Diseases]] (NIAID), which is a division of the [[National Institutes of Health]] (NIH), and the pharmaceutical company [[Merck & Co.]] Merck developed V520 to stimulate HIV-specific cellular immunity, which prompts the body to produce T cells that kill HIV-infected cells. In previous smaller trials, this vaccine was found to be safe, because of the lack of adverse effects on the participants. The vaccine showed induced cellular immune responses against HIV in more than half of volunteers.<ref name="AIDSepidemicupdate">{{cite web|author=Joint United Nations Programme on HIV/AIDS ([[UNAIDS]])|date=December 2005|title=AIDS epidemic update|url=https://www.who.int/hiv/epi-update2005_en.pdf|access-date=2014-04-22|publisher=[[World Health Organization]]|archive-date=2014-06-29|archive-url=https://web.archive.org/web/20140629031433/http://www.who.int/hiv/epi-update2005_en.pdf|url-status=live}}</ref> V520 contains a weakened [[adenovirus]] that serves as a carrier for three subtype B HIV genes (''gag,'' ''pol'' and ''nef''). Subtype B is the most prevalent HIV subtype in the regions of the study sites. Adenoviruses are among the main causes of upper respiratory tract ailments such as the [[common cold]]. Because the vaccine contains only three HIV genes housed in a weakened adenovirus, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. It was announced in September 2007 that the trial for V520 would be stopped after it determined that vaccination with V520 appeared associated with an increased risk of HIV infection in some recipients.<ref>[http://www.hvtn.org/science/step_buch.html Efficacy Results from the STEP Study (Merck V520 Protocol 023/HVTN 502): A Phase II Test-of-Concept Trial of the MRKAd5 HIV-1 Gag/Pol/Nef Trivalent Vaccine] {{webarchive|url=https://web.archive.org/web/20110726164651/http://www.hvtn.org/science/step_buch.html |date=2011-07-26 }}</ref> The foremost issue facing the recombinant adenovirus that was used is the high prevalence of the adenovirus-specific antibodies as a result of prior exposure to adenovirus. Adenovirus vectors and many other [[viral vector vaccine|viral vectors]] currently used in HIV vaccines will induce a rapid memory immune response against the vector. This results in an impediment to the development of a T cell response against the inserted antigen (HIV antigens)<ref>{{cite journal | vauthors = Sekaly RP | title = The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development? | journal = The Journal of Experimental Medicine | volume = 205 | issue = 1 | pages = 7–12 | date = January 2008 | pmid = 18195078 | pmc = 2234358 | doi = 10.1084/jem.20072681 }}</ref> The results of the trial prompted the reexamination of vaccine development strategies.<ref name="pmid18597681">{{cite journal | vauthors = Iaccino E, Schiavone M, Fiume G, Quinto I, Scala G | title = The aftermath of the Merck's HIV vaccine trial | journal = Retrovirology | volume = 5 | page = 56 | date = July 2008 | pmid = 18597681 | pmc = 2483718 | doi = 10.1186/1742-4690-5-56 | doi-access = free }}</ref>
* [[HVTN 505]], a Phase IIb study, was launched in 2009 but halted in 2013 due to meeting requirements of futility.
* Potential broadly neutralizing antibodies have been cloned in the laboratory (monoclonal antibodies) and are being tested in [[passive immunity|passive vaccination]] [[clinical trial]]s.<ref name=eOD-GT8>{{Cite web|last=International AIDS Vaccine Initiative|date=2021-09-29|others=ModernaTX, Inc., The University of Texas at San Antonio, George Washington University, Fred Hutchinson Cancer Research Center, Emory University|title=A Phase 1, Randomized, First-in-human, Open-label Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) in HIV-1 Uninfected Adults in Good General Health|url=https://clinicaltrials.gov/ct2/show/NCT05001373|access-date=2021-11-30|archive-date=2021-11-30|archive-url=https://web.archive.org/web/20211130203340/https://clinicaltrials.gov/ct2/show/NCT05001373|url-status=live}}</ref> In May 2016, there was the launch of the Antibody Mediated Prevention (AMP) trials (HVTN 703 and HVTN 704), the first phase IIb trials of a monoclonal antibody for HIV prevention. HVTN 703 and HVTN 704 found that the VRC01 monoclonal antibody, which targets the CD4 binding site, was not able to prevent HIV acquisition.<ref>{{Cite journal|last1=Corey|first1=Lawrence|last2=Gilbert|first2=Peter B.|last3=Juraska|first3=Michal|last4=Montefiori|first4=David C.|last5=Morris|first5=Lynn|last6=Karuna|first6=Shelly T.|last7=Edupuganti|first7=Srilatha|last8=Mgodi|first8=Nyaradzo M.|last9=deCamp|first9=Allan C.|last10=Rudnicki|first10=Erika|last11=Huang|first11=Yunda|date=2021-03-18|title=Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition|journal=The New England Journal of Medicine|volume=384|issue=11|pages=1003–1014|doi=10.1056/NEJMoa2031738|issn=1533-4406|pmc=8189692|pmid=33730454}}</ref>
* In 2017, Janssen and the HVTN launched the phase IIb trial called HVTN 705/Imbokodo, testing the mosaic vector vaccine Ad26.Mos4.HIV and the aluminum phosphate-adjuvanted Clade C gp140 vaccines which are designed to prevent infection of all HIV subtypes around the world.<ref>{{Cite web|url=https://www.firstpost.com/tech/science/candidate-for-new-aids-vaccine-advances-to-next-phase-of-pre-approval-trials-4690471.html|title=Candidate for new AIDS vaccine advances to next phase of pre-approval trials|website=Tech2|language=en-US|access-date=2018-07-11|date=2018-07-08|archive-date=2018-07-11|archive-url=https://web.archive.org/web/20180711225342/https://www.firstpost.com/tech/science/candidate-for-new-aids-vaccine-advances-to-next-phase-of-pre-approval-trials-4690471.html|url-status=live}}</ref> In 2021 the [[NIH]] announced that the Imbokodo Phase 2b study did not provide statistically significant reduction in HIV infection.<ref name=nih2021>{{cite web |title=HIV Vaccine Candidate Does Not Sufficiently Protect Women Against HIV Infection |url=https://www.nih.gov/news-events/news-releases/hiv-vaccine-candidate-does-not-sufficiently-protect-women-against-hiv-infection |website=National Institutes of Health (NIH) |access-date=1 September 2021 |language=EN |date=31 August 2021 |archive-date=31 August 2021 |archive-url=https://web.archive.org/web/20210831235052/https://www.nih.gov/news-events/news-releases/hiv-vaccine-candidate-does-not-sufficiently-protect-women-against-hiv-infection |url-status=live }}</ref>
* In 2019, Terevac-VIH, a vaccine from Cuba, was determined to have passed the first stage of clinical trials after two years and move to the second stage of development.<ref>{{Cite web |url=https://thegeekherald.com/p/cure-for-hiv-aids-cuba-makes-a-breakthrough-nih-and-gate-foundation-will-donate-for-future-research/ |title=Cure for HIV/AIDS: Cuba makes a Breakthrough, NIH and Gate Foundation will Donate for Future Research |date=27 December 2019 |access-date=2021-12-11 |archive-date=2021-12-11 |archive-url=https://web.archive.org/web/20211211203908/https://thegeekherald.com/p/cure-for-hiv-aids-cuba-makes-a-breakthrough-nih-and-gate-foundation-will-donate-for-future-research/ |url-status=live }}</ref><ref>{{Cite web |url=https://www.cmhw.cu/en/science-and-health/5289-successful-clinical-trials-of-hiv-vaccine-in-cuba |title=Successful Clinical Trials of HIV Vaccine in Cuba |access-date=2021-12-11 |archive-date=2021-12-11 |archive-url=https://web.archive.org/web/20211211203244/https://www.cmhw.cu/en/science-and-health/5289-successful-clinical-trials-of-hiv-vaccine-in-cuba |url-status=live }}</ref>

''Therapeutic HIV vaccines''

Biosantech developed a therapeutic vaccine called Tat Oyi, which targets the tat protein of HIV. It was tested in France in a double-blind Phase I/II trial with 48 HIV-positive patients who had reached viral suppression on [[Highly active antiretroviral therapy|Highly Active Antiretroviral Therapy]] and then stopped antiretrovirals after getting the intradermal Tat Oyi vaccine.<ref>{{cite journal | vauthors = Loret EP, Darque A, Jouve E, Loret EA, Nicolino-Brunet C, Morange S, Castanier E, Casanova J, Caloustian C, Bornet C, Coussirou J, Boussetta J, Couallier V, Blin O, Dussol B, Ravaux I | display-authors = 6 | title = Intradermal injection of a Tat Oyi-based therapeutic HIV vaccine reduces of 1.5 log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART interruption in a phase I/II randomized controlled clinical trial | journal = Retrovirology | volume = 13 | page = 21 | date = April 2016 | pmid = 27036656 | pmc = 4818470 | doi = 10.1186/s12977-016-0251-3 | doi-access = free }}</ref>