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IAVI Report : Newsletter on... 2010
Topics: AIDS Vaccines; Antibodies, Neutralizing; Humans
PubMed: 21158223
DOI: No ID Found -
Expert Opinion on Biological Therapy Mar 2017Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review... (Review)
Review
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses. The follow-up pox-protein trials, developed to replicate and enhance the polyfunctional antibody responses induced by the RV144 regimen, are already reaching efficacy trials, while a large body of work providing a more complete understanding of the development of broadly neutralizing antibodies is now being translated into immunogen design using several different strategies. T-cell based vaccines, fallen out of favor after Ad5-based trials showed increased infection rates in Ad5 seropositive vaccine recipients, are experiencing a comeback based in part on the promising results from non-human primate challenge studies using rhCMV-based immunogens. This diverse array of vaccine candidates may finally allow us to identify a broadly effective HIV vaccine able to contain the epidemic.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; HIV Antibodies; HIV Infections; HIV-1; Humans
PubMed: 28095712
DOI: 10.1080/14712598.2017.1282457 -
AIDS Research and Therapy Sep 2017Vesicular stomatitis virus (VSV), like many other Rhabdoviruses, have become the focus of intense research over the past couple of decades based on their suitability as... (Review)
Review
Vesicular stomatitis virus (VSV), like many other Rhabdoviruses, have become the focus of intense research over the past couple of decades based on their suitability as vaccine vectors, transient gene delivery systems, and as oncolytic viruses for cancer therapy. VSV as a vaccine vector platform has multiple advantages over more traditional viral vectors including low level, non-pathogenic replication in diverse cell types, ability to induce both humoral and cell-mediate immune responses, and the remarkable expression of foreign proteins cloned into multiple intergenic sites in the VSV genome. The utility and safety of VSV as a vaccine vector was recently demonstrated near the end of the recent Ebola outbreak in West Africa where VSV pseudotyped with the Ebola virus (EBOV) glycoprotein was proven safe in humans and provided protective efficacy against EBOV in a human phase III clinical trial. A team of Canadian scientists, led by Dr. Gary Kobinger, is now working with International AIDS Vaccine Initiative (IAVI) in developing a VSV-based HIV vaccine that will combine unique Canadian research on the HIV-1 Env glycoprotein and on the VSV vaccine vector. The goal of this collaboration is to develop a vaccine with a robust and potent anti-HIV immune response with an emphasis on generating quality antibodies to protect against HIV challenges.
Topics: AIDS Vaccines; Animals; Genetic Vectors; Guinea Pigs; HIV Antibodies; HIV Envelope Protein gp120; HIV-1; Humans; Immunity, Humoral; Macaca; Mice; Vesicular stomatitis Indiana virus
PubMed: 28893277
DOI: 10.1186/s12981-017-0179-2 -
Expert Review of Vaccines Jun 2015Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign... (Review)
Review
Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing broadly neutralizing antibodies has fueled research in the design and synthesis of new, well-defined antigenic constructs for the development of HIV envelope-directed vaccines. The present review will cover previous and recent efforts toward the design of synthetic vaccines based on the HIV viral envelope glycoproteins, with special emphasis on examples from our own laboratories. The biological evaluation of some of the most representative vaccine candidates, in terms of their antigenicity and immunogenicity, will also be discussed to illustrate the current state-of-the-art toward the development of fully synthetic HIV vaccines.
Topics: AIDS Vaccines; Antibodies, Neutralizing; HIV Antibodies; HIV Infections; Humans; Vaccines, Synthetic
PubMed: 25824661
DOI: 10.1586/14760584.2015.1027690 -
Journal of the Pediatric Infectious... May 2022Our study explores the understanding of vaccine-induced seropositivity (VISP) and its potential impact on US adolescents' and caregivers' willingness to participate in...
Our study explores the understanding of vaccine-induced seropositivity (VISP) and its potential impact on US adolescents' and caregivers' willingness to participate in adolescent HIV vaccine clinical trials. Findings from in-depth interviews suggest that addressing concerns about VISP will be essential for future pediatric HIV vaccine trials in the United States.
Topics: AIDS Vaccines; Adolescent; Child; HIV Infections; Health Knowledge, Attitudes, Practice; Humans; United States
PubMed: 35139223
DOI: 10.1093/jpids/piac001 -
Human Vaccines & Immunotherapeutics Sep 2012The RV144 phase III clinical trial with the combination of the poxvirus vector ALVAC and the HIV gp120 protein has taught us that a vaccine against HIV/AIDS is possible... (Review)
Review
The RV144 phase III clinical trial with the combination of the poxvirus vector ALVAC and the HIV gp120 protein has taught us that a vaccine against HIV/AIDS is possible but further improvements are still needed. Although the HIV protective effect of RV144 was modest (31.2%), these encouraging results reinforce the use of poxvirus vectors as HIV/AIDS vaccine candidates. In this review we focus on the prophylactic clinical studies thus far performed with the more widely studied poxvirus vectors, ALVAC, MVA, NYVAC and fowlpox expressing HIV antigens. We describe the characteristics of each vector administered either alone or in combination with other vectors, with emphasis on the immune parameters evaluated in healthy volunteers, percentage of responders and triggering of humoral and T cell responses. Some of these immunogens induced broad, polyfunctional and long-lasting CD4(+) and CD8(+) T cell responses to HIV-1 antigens in most volunteers, with preference for effector memory T cells, and neutralizing antibodies, immune parameters that might be relevant in protection. Finally, we consider improvements in immunogenicity of the poxvirus vectors by the selective deletion of viral immunomodulatory genes and insertion of host range genes in the poxvirus genome. Overall, the poxvirus vectors have proven to be excellent HIV/AIDS vaccine candidates, with distinct behavior among them, and the future implementation will be dictated by their optimized immune profile in clinical trials.
Topics: AIDS Vaccines; Clinical Trials, Phase III as Topic; Genetic Vectors; HIV Antigens; Humans; Poxviridae
PubMed: 22906946
DOI: 10.4161/hv.20778 -
Journal of Molecular Biology May 2019Antigenic mimicry is a fundamental tenet of structure-based vaccinology. Vaccine strategies for the human immunodeficiency virus type 1 (HIV-1) focus on the mimicry of... (Review)
Review
Antigenic mimicry is a fundamental tenet of structure-based vaccinology. Vaccine strategies for the human immunodeficiency virus type 1 (HIV-1) focus on the mimicry of its envelope spike (Env) due to its exposed location on the viral membrane and role in mediating infection. However, the virus has evolved to minimize the immunogenicity of conserved epitopes on the envelope spike. This principle is starkly illustrated by the presence of an extensive array of host-derived glycans, which act to shield the underlying protein from antibody recognition. Despite these hurdles, a subset of HIV-infected individuals eventually develop broadly neutralizing antibodies that recognize these virally presented glycans. Effective HIV-1 immunogens are therefore likely to involve some degree of mimicry of both the protein and glycan components of Env. As such, considerable efforts have been made to characterize the structure of the envelope spike and its glycan shield. This review summarizes the recent progress made in this field, with an emphasis on our growing understanding of the factors shaping the glycan shield of Env derived from both virus and soluble immunogens. We argue that recombinant mimics of the envelope spike are currently capable of capturing many features of the native viral glycan shield. Finally, we explore strategies through which the immunogenicity of Env glycans may be enhanced in the development of future immunogens.
Topics: AIDS Vaccines; Antibodies, Neutralizing; Epitopes; HIV Infections; HIV-1; Humans; Models, Molecular; Molecular Mimicry; Polysaccharides; env Gene Products, Human Immunodeficiency Virus
PubMed: 31028779
DOI: 10.1016/j.jmb.2019.04.016 -
Archives of Virology Nov 2020New HIV infections continue relentlessly in southern Africa, demonstrating the need for a vaccine to prevent HIV subtype C. In South Africa, the country with the highest... (Review)
Review
New HIV infections continue relentlessly in southern Africa, demonstrating the need for a vaccine to prevent HIV subtype C. In South Africa, the country with the highest number of new infections annually, HIV vaccine research has been ongoing since 2003 with collaborative public-private-philanthropic partnerships. So far, 21 clinical trials have been conducted in South Africa, investigating seven viral vectors, three DNA plasmids, four envelope proteins, five adjuvants and three monoclonal antibodies. Active vaccine candidates have spanned subtypes A, B, C, E and multi-subtype mosaic sequences. All were well tolerated. Four concepts were investigated for efficacy: rAd5-gag/pol/nef showed increased HIV acquisition in males, subtype C ALVAC/gp120/MF59 showed no preventative efficacy, and the trials for the VRC01 monoclonal antibody and Ad26.Mos4.HIV/subtype C gp140/ aluminum phosphate are ongoing. Future trials are planned with DNA/viral vector plus protein combinations in concert with pre-exposure prophylaxis, and sequential immunization studies with transmitted/founder HIV envelope to induce broadly neutralizing antibodies. Finally, passive immunization trials are underway to build on the experience with VRC01, including single and combination antibody trials with an antibody derived from a subtype-C-infected South African donor. Future consideration should be given to the evaluation of novel strategies, for example, inactivated-whole-virus vaccines.
Topics: AIDS Vaccines; Antibodies, Monoclonal; HIV Infections; Humans; Immunization, Passive; Randomized Controlled Trials as Topic; South Africa; Treatment Outcome; Vaccination
PubMed: 32797338
DOI: 10.1007/s00705-020-04777-2 -
Human Vaccines & Immunotherapeutics Nov 2012High safety marks for Merck’s Gardasil Cuba tests prostate cancer vaccine HIV’s weak spot: V2 Unique anti-cancer agent ColoAd1 enters the clinic Broadly neutralizing...
High safety marks for Merck’s Gardasil Cuba tests prostate cancer vaccine HIV’s weak spot: V2 Unique anti-cancer agent ColoAd1 enters the clinic Broadly neutralizing antibodies against influenza A and B discovered Clinical trials initiated: Nexvax2 therapeutic vaccine for celiac disease The 20 top-selling vaccines in the first half of 2012 Influenza vaccine safe for pregnant women
Topics: AIDS Vaccines; Antibodies, Neutralizing; Cancer Vaccines; Celiac Disease; Female; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; Humans; Influenza, Human; Male; Papillomavirus Vaccines; Prostatic Neoplasms; Vaccines
PubMed: 23151443
DOI: 10.4161/hv.22753 -
Current Opinion in HIV and AIDS Sep 2013The development of a preventive HIV vaccine remains an unresolved challenge. Animal models that can predict the results of HIV vaccine efficacy trials and identify the... (Review)
Review
PURPOSE OF REVIEW
The development of a preventive HIV vaccine remains an unresolved challenge. Animal models that can predict the results of HIV vaccine efficacy trials and identify the immune mechanisms responsible for vaccine protection would be most useful for HIV vaccine development. The purpose of the current review is to critique recent developments in the use of animal models of HIV infection in preclinical studies of AIDS vaccines and to describe how the use of improved animal models can inform the development of an HIV vaccine.
RECENT FINDINGS
The results of preclinical experiments with candidate HIV vaccines can vary with the SIV challenge virus used. It is now known that there is considerable variability in the neutralization sensitivity and that the level of viral sequence diversity within the challenge stocks varies. This has allowed more realistic preclinical vaccine studies with heterologous vaccine antigens and challenge viruses. Further, the dose of challenge virus and the route of virus challenge can modify the efficacy of candidate vaccines in preclinical studies.
SUMMARY
Recent experiments demonstrate that nonhuman primate models of AIDS can reproduce the complex biology of HIV transmission, recapitulate the results of HIV vaccine efficacy trials in humans and be used to identify correlates of protection.
Topics: AIDS Vaccines; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; HIV Infections; Primates
PubMed: 23836045
DOI: 10.1097/COH.0b013e328363d3a2