ll Scienc Ce e f & o T l h a e n r a r a p p u u y y o o J J Journal of Cell Science & Therapy Asif and Irshad, J Cell Sci Ther 2017, 8:2 ISSN: 2157-7013 DOI: 10.4172/2157-7013. 1000265 Review Article Open Access Efficacy Trials and Progress of HIV Vaccines Daud Faran Asif1*, and Irshad M2 1Department of Biochemistry and Biotechnology, University of Gujrat, Pakistan 2Department of Biotechnology, University of Gujrat, Gujrat, Pakistan *Corresponding author: Daud Faran Asif, BS. Hons Student, Department of Biochemistry and Biotechnology, University of Gujrat, Pakistan, Tel: 92533643112; E-mail: [email protected] Rec date: Mar 18, 2017; Acc date: Apr 01, 2017; Pub date: Apr 04, 2017 Copyright: © 2017 Asif DF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Discovery of HIV as causative agent of AIDS let to the belief that a vaccine for AIDS will be available shortly but was not that easy, and it took more than 30 years of hard laboratory and clinical work toward HIV vaccine development. Efficacy trials of RV144 and their results revealed that HIV vaccine is accomplishable. Clinical trials for developing bNAbs has monoclonal antibodies and to increase its half-life are also underway to achieve a proper HIV vaccine. In this review article, we see that how these efficacy trials are highlighting HIV vaccine concepts in clinical development. Therapeutic vaccines are proving to be a functional cure toward HIV treatment and progress is ongoing in such HIV vaccine development which will attack HIV before it fuses with cell and cause infection thus preventing AIDS. So, in near future it will be possible to cure HIV and bring an end to this epidemic. Keywords: HIV vaccine; Clinical trials; AIDS; Efficacy trials of have a near normal life expectancy. In the first 15-20 years of the RV144 pandemic, during a time when effective ART was unavailable or in its infancy, there was intense scientific interest and inquiry into molecular Introduction mechanisms of HIV replication, in order to develop effective drugs with which to inhibit HIV replication in vivo. In the past 15 years, When HIV (Human Immunodeficiency virus) was discovered and multiple drugs in multiple classes have been developed and much has established as the causative agent of AIDS in 1983-1984 [1], the been learned about how best to use combinations of agents. Now it is majority of people thought that vaccines against this HIV would be possible, and even expected, that clinical viral suppression can be developed and applied rapidly. But, this was not going to happen in achieved, with consequent immune reconstitution. However, treated case of HIV as in AIDS, virus-induced immune response possesses no individuals still have excess morbidity and mortality when compared ability to prevent re-infection and also not capable of slowing down the to uninfected persons, due largely to accelerated aging and age related progression to disease. The development of an HIV vaccine took diseases such as cardiovascular disease, metabolic syndrome solid almost 30 years of intense laboratory and clinical work. And because of organ malignancies, neurocognitive and functional decline and this intense work, today we are closer to develop an HIV vaccine but, it osteoporosis. is difficult to predict the time when we have the vaccine that possesses sufficient efficacy for implementation in public health programs [2]. Development of an HIV Vaccine: A Difficult Challenge Why HIV vaccine is needed? The development of a safe and highly effective vaccine against HIV has been a difficult challenge because of the ability of HIV to escape To stop the spread of AIDS caused by HIV, we have to stop the host immune response. There are three main scientific challenges for occurrence of new HIV infections. For preventing new HIV infections the development of an HIV vaccine. These challenges include following from occurring, several preventive measures are applied, but these [7-9]: preventive measures have some shortcomings, e.g. although condom use and sterile needles have a strong impact, but they possess The immunological correlates of protection against HIV/ insufficient adherence and access that limit their impact [3]. Other AIDS are unknown preventive measures, including male circumcision, pre-prophylaxis (PreP) and Antiretroviral therapy (ART) [4-6] have encountered the In most diseases that are prevented by vaccines, there is a same problems of limited access and adherence. Vaccination does not correlation between the immune responses induced by vaccines and involve such problems so it is preferred over other preventive the protection against disease or infection. But in case of HIV virus in measures. Also, vaccination possesses the ability to eradicate the virus, contrast to this correlation, broad range of immune responses is because of this ability it has been the major goal to develop an HIV developed against HIV in people infected with this virus. These vaccine to prevent new infections from occurring [3]. In the past immune responses are not able to either eradicate the infection or to 33 years of the HIV pandemic, there has been monumental progress in inhibit the progress towards AIDS [10]. The current development the clinical management of HIV disease. Once considered a death strategies of an HIV vaccine are directed at the induction of humoral sentence due to the inexorable decline in CD4 T cell number and and cellular immunity and these strategies, also involve the induction function over time ultimately leading to AIDS, patients with HIV of both major types of immune responses (humoral and cellular). infection who have access to effective antiretroviral therapy (ART) now Although it is a difficult challenge, but it is not an impossible target to J Cell Sci Ther, an open access journal Volume 8 • Issue 2 • 1000265 ISSN: 2157-7013 Citation: Asif DF, Irshad M (2017) Efficacy Trials and Progress of HIV Vaccines. J Cell Sci Ther 8: 265. doi:10.4172/2157-7013. 1000265 Page 2 of 11 achieve. There has been the evidence that the early stages of These earlier trials intended to target at the production of transmission of HIV are susceptible to intervention of immune neutralizing antibodies but in these experiments, difficulties were response [11]. The first experiment involving the immunization of reported with the immunogen. Then the focus of an HIV vaccines humans against HIV-Ι (a strain of HIV) begun in November 1986 turned on to cytotoxic T-lymphocytes (CTLs) [12-17]. Because in involving a sufficient number of HIV healthy volunteers. In this immune system cytotoxic T-lymphocytes play a significant role in experiment, vaccinia virus recombinant (V25) that expresses gp160 controlling the levels of virus during the natural infection of HIV. So, env at the surface of infected cells are applied. gp160 env are the targeting CTLs has also been a preference for research and determinants of HTLVΙΙΙB. The results of this experiment showed that development of HIV vaccine [3]. The development of an HIV vaccine the immune response against HIV can be achieved in humans [12]. is a difficult challenge because of lengthy, time consuming and Following this experiment, almost more than 256 clinical trials (phase expensive clinical trials for testing HIV candidate vaccines. In spite of Ι and phase ΙΙ) including over 44, 000 healthy volunteers have tested the difficult and enormous challenge, the recent success provides a way candidate vaccines against HIV [12-17]. Among these clinical trials, forward towards the development of vaccine against HIV [3] (Table 1). only six candidate vaccines have achieved clinical efficacy. These six vaccines include VAX004, VAX003, Phambali, HVTN505 and RV144 [18]. HIV vaccine efficacy trial Expected immune Trial Name Trial duration Phase type Type of vaccine Outcome response VAX004 1998-2003 ΙΙΙ rpg120 (clade B) Humoral No efficacy VAX003 1999-2003 ΙΙΙ rgp120 (clades B+E) Humoral No efficacy Enhanced HIV infection risk 2004-2007 (Stopped for possible Step ΙΙb Cellular in uncircumcised men and enhancement in HIV acquisition) MSM Phambili 2007 ΙΙb rAD5 (gag/pollnef) Cellular No efficacy Cellular along with RV 144 2003-2009 ΙΙΙ Canarypox (gag/pollnef) 31.2% efficacy humoral DNA Humoral as well as HTVN 505 2009-2015 ΙΙb No efficacy plasmid (gag/pollneflenv) cellular +rAD5 (gag/pollen) Table 1: Illustrating the trials of different HIV vaccines and their outcomes [18; p3]. Presence of genetic variability in HIV The deficit of appropriate animal models The genetic analysis of HIV strains that are isolated from different Many experimental HIV vaccines have produced different parts of the world has disclosed that many genes present in HIV intensities of protection in non-human primate models involving display wide sequence heterogeneity specifically in the genes that Chimpanzees that are exposed with HIV and monkeys that are encode viral envelope proteins gp120 and gp41. As a result of this exposed to SIV; an analogous to HIV. The basic problem is that heterogeneity, the strains of HIV-Ι are divided into groups and different experiment vaccines generate dissimilar results in these two subtypes. Most of HIV infection are caused by viruses of HIV-Ι group models involving chimpanzees and monkeys. It is also not clear that M that is further divided into 9 subtypes from A-J. There is also a the results from these models would predict vaccine induced chance of generation of unique circulating recombinant forms (CRFs) protection in humans. Such information regarding vaccine induced as a result of recombination among viruses of different subtypes. protection will only result from trials involving humans. Although, there is much knowledge about the genetic variability present in HIV strains but it is not clear about the relationship that is Brief History of HIV vaccine development found between genetic variability and the vaccine induced protection against infection [10].