HIV vaccines: Progress to date
HIV Immunovirology Laboratory, St Vincent's Centre for Applied Medical Research, Sydney, New South Wales, Australia. Drugs
(Impact Factor: 4.34).
03/2011; 71(4):387-414. DOI: 10.2165/11585400-000000000-00000
The quest for an effective and safe HIV-1 vaccine has been and still is the aspiration of many scientists and clinicians worldwide. Until recently, the hopes for an effective vaccine were thwarted by the disappointing results and early termination in September 2007 of the STEP study, which saw a subgroup of male vaccine recipients at an increased risk of HIV-1 infection, and the failure of earlier trials of vaccines based on recombinant envelope proteins to provide any level of protection. The results of the STEP study raised important questions in the field of HIV vaccines, including the use of recombinant adenovirus vectors as immunogens, the rationale for the development of T-cell-based vaccines and the development pathway for these vaccines, in terms of assessment of immunogenicity and the challenge models used. The study of neutralizing antibodies has demonstrated that the induction of high-titre, broadly neutralizing antibodies in the majority of recipients is likely to be highly problematic. However, the results of the RV144 Thai trial released in September 2009 have brought new optimism to the field. This study employed envelope-based immunogens delivered as a priming vaccination with a recombinant poxvirus vector and boosting with recombinant proteins. This regimen provided modest protection to HIV-1 infection in a low-risk population. Although the correlates of protection are currently unknown, extensive studies are underway to try to determine these. Neutralizing antibodies were not induced in the RV144 study; however, considerable titres of binding antibodies to HIV-1 viral envelope (Env) were. It is speculated that these antibodies may have provided a means of protection by a mechanism such as antibody-dependent cell-mediated cytotoxicity. In addition, no CD8+ T-cell responses were induced, but robust CD4+ T-cell responses were, and correlates of protection are being sought by analysing the quality of this aspect of the vaccine-induced immune response. The current paradigm for an optimal HIV-1 vaccine is to design immunogens and vaccination protocols that allow the induction of both broadly neutralizing humoral and broadly reactive and effective cell-mediated immunity, to act at sites of possible infection and post-infection, respectively. However, this is challenged by the results of the RV144 trial as neither of these responses were induced but modest protection was observed. Understanding the biology and immunopathology of HIV-1 early following infection, its modes of transmission and the human immune system's response to the virus should aid in the rational design of vaccines of increased efficacy.
Available from: Maria Angeles Muñoz-Fernández
- "For over 20 years, the scientific community has been working hard to develop new preventive strategies to decrease HIV infection rates, especially in women. To date, despite a great deal of effort, there are no effective vaccines against HIV infection (Munier et al., 2011). Thus, it is urgent and imperative to develop prevention systems capable of stopping the spread of HIV in the most disadvantaged and vulnerable populations, especially during sexual intercourse (Anton, 2012; Stephenson, 2011). "
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ABSTRACT: More than three decades since its discovery, HIV infection remains one of the most aggressive epidemics worldwide, with more than 35 million people infected. In sub-Saharan Africa, heterosexual transmissions represent nearly 80% of new infections, with 50% of these occurring in women. In an effort to stop the dramatic spread of the HIV epidemic, new preventive treatments, such as microbicides, have been developed. Nanotechnology has revolutionized this field by designing and engineering novel highly effective nano-sized materials as microbicide candidates. This review illustrates the most recent advances in nanotech-derived HIV prevention strategies, as well as the main steps required to translate promising in vitro results into clinical trials.
Copyright © 2014 Elsevier B.V. All rights reserved.
Available from: PubMed Central
- "Viral infections are responsible for causing a significant number of human diseases, epidemic outbreaks, morbidity, and mortality. While vaccine efforts have proven successful for preventing and eradicating some viral infections, many viruses cannot be targeted by immunization, including dengue virus (DENV), human cytomegalovirus (HCMV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV) [1-5]. Alternative means of control include the use of antiviral drugs; however, there are currently few licensed and efficacious drugs available for prophylactic and therapeutic antiviral treatments. "
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ABSTRACT: We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry.
Extensive analysis of the tannins' mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at muM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses.
CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.
Available from: europepmc.org
- "There have been several attempts to
develop a prophylaxis vaccine for HIV infection over the past
few decades. However, the hurdles for developing any type of
vaccine for this pathology have been daunting
22]. This is
also true for peptide derived vaccines. "
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ABSTRACT: In silico tools are employed to examine the evolutionary relationship to possible vaccine peptide candidates' development. This perspective sheds light on the proteomic changes affecting the creation of HLA specific T-cell stimulating peptide vaccines for HIV. Full-length sequences of the envelope protein of the HIV subtypes A, B, C and D were obtained through the NCBI Protein database were aligned using CLUSTALW. They were then analyzed using RANKPEP specific to Human Leukocyte Antigen A*02 and B*27. Geneious was used to catalogue the collected gp160 sequences and to construct a phylogenic tree. Mesquite was employed for ancestral state reconstruction to infer the order of amino acid substitutions in the epitopes examined. The results showed that consensus peptide identified SLAEKNITI had changes that indicated predicted escape mutation in strains of HIV responding to pressure exerted by CD8+ cells expressing HLA A*02. The predominating 9-mers IRIGPGQAF of gp120 are significantly less immunogenic toward HLA B*27 than to HLA A*02. The data confirms previous findings on the importance for efficacious binding, of an arginine residue at the 2(nd) position of the gag SL9 epitope, and extends this principle to other epitopes which interacts with HLA B*27. This study shows that the understanding of viral evolution relating T-cell peptide vaccine design is a development that has much relevance for the creation of personalized therapeutics for HIV treatment.
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