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AIDS Research and Human Retroviruses Nov 2013This article discusses HIV vaccine discovery and candidate vaccine testing in the context of current realities of funding and clinical trial practice. Lacking perfect... (Review)
Review
This article discusses HIV vaccine discovery and candidate vaccine testing in the context of current realities of funding and clinical trial practice. Lacking perfect animal models for testing candidate HIV vaccines, clinical investigators have proposed a strategy of iterative exploratory clinical trials in the model of cancer chemotherapy development. Problems with the appropriateness of this model to HIV vaccine development are discussed. Also, the future feasibility of this strategy in the context of increasing clinical trial costs and emerging new, efficacious prevention modalities is questioned. Strategies for making better use of animal models are presented as an alternative to iterative exploratory clinical efficacy testing. Some ways in which better data from preclinical studies can refine clinical product development are described. Finally, development of an HIV vaccine under the FDA's "Animal Rule" pathway to licensure when human efficacy studies are not feasible is discussed as a fall-back approach. Not making a preventive vaccine against HIV infection is simply not an option because eradication of AIDS will require a preventive vaccine.
Topics: AIDS Vaccines; Animals; Drug Discovery; Drug Evaluation; Drug Evaluation, Preclinical; HIV Infections; Humans; Models, Animal
PubMed: 23379343
DOI: 10.1089/AID.2012.0337 -
AIDS (London, England) Jun 2012There is renewed optimism that the goal of developing a highly effective AIDS vaccine is attainable. The HIV-1 vaccine field has seen its first trial of a vaccine... (Review)
Review
There is renewed optimism that the goal of developing a highly effective AIDS vaccine is attainable. The HIV-1 vaccine field has seen its first trial of a vaccine candidate that prevents infection. Although modest in efficacy, this finding, along with the recent discovery that the human immune system can produce broadly neutralizing antibodies capable of inhibiting greater than 90% of circulating viruses, provides a guide for the rational design of vaccines and protection by passive immunization. Together, these findings will help shape the next generation of HIV vaccines.
Topics: AIDS Vaccines; Animals; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Drug Design; HIV Infections; HIV-1; Humans; Research Design; Treatment Outcome; Vaccines, Synthetic
PubMed: 22706011
DOI: 10.1097/QAD.0b013e32835474d2 -
AIDS Research and Human Retroviruses Nov 2015An overall decrease of HIV prevalence is now observed in several key Asian countries due to effective prevention programs. The decrease in HIV prevalence and incidence... (Review)
Review
An overall decrease of HIV prevalence is now observed in several key Asian countries due to effective prevention programs. The decrease in HIV prevalence and incidence may further improve with the scale-up of combination prevention interventions. The implementation of future prevention trials then faces important challenges. The opportunity to identify heterosexual populations at high risk such as female sex workers may rapidly wane. With unabating HIV epidemics among men who have sex with men (MSM) and transgender (TG) populations, an effective vaccine would likely be the only option to turn the epidemic. It is more likely that efficacy trials will occur among MSM and TG because their higher HIV incidence permits smaller and less costly trials. The constantly evolving patterns of HIV-1 diversity in the region suggest close monitoring of the molecular HIV epidemic in potential target populations for HIV vaccine efficacy trials. CRF01_AE remains predominant in southeast Asian countries and MSM populations in China. This relatively steady pattern is conducive to regional efficacy trials, and as efficacy warrants, to regional licensure. While vaccines inducing nonneutralizing antibodies have promise against HIV acquisition, vaccines designed to induce broadly neutralizing antibodies and cell-mediated immune responses of greater breadth and depth in the mucosal compartments should be considered for testing in MSM and TG. The rationale and design of efficacy trials of combination prevention modalities such as HIV vaccine and preexposure prophylaxis (PrEP) remain hypothetical, require high adherence to PrEP, are more costly, and present new regulatory challenges. The prioritization of prevention interventions should be driven by the HIV epidemic and decided by the country-specific health and regulatory authorities. Modeling the impact and cost-benefit may help this decision process.
Topics: AIDS Vaccines; Asia; Clinical Trials as Topic; Disease Transmission, Infectious; Epidemics; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Prevalence; Transgender Persons
PubMed: 26107771
DOI: 10.1089/aid.2015.0049 -
IAVI Report : Newsletter on... 2012
Topics: AIDS Vaccines; Humans; Research
PubMed: 22448403
DOI: No ID Found -
Current Opinion in HIV and AIDS Jul 2013In this review, examples of recent progress in HIV-1 vaccine research are discussed. (Review)
Review
PURPOSE OF REVIEW
In this review, examples of recent progress in HIV-1 vaccine research are discussed.
RECENT FINDINGS
New insights from the immune correlates analyses of the RV144 efficacy trial have accelerated vaccine development with leads to follow in nonhuman primate studies and improved vaccine designs. Several new vaccine vector approaches offer promise in the exquisite control of acute infection and in improving the breadth of T-cell responses. New targets of broadly neutralizing antibodies (BnAbs) have been elucidated, and improved understanding of how the human host controls BnAb development have emerged from BnAb knock-in mice and from analyses of BnAb maturation and virus evolution in individuals followed from the time of HIV-1 transmission to BnAb induction.
SUMMARY
Based on these observations, it is clear that the development of a successful HIV-1 vaccine will require new vaccine approaches and iterative testing of immunogens in well designed animal and human trials.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; HIV Infections; HIV-1; Humans; Macaca
PubMed: 23743722
DOI: 10.1097/COH.0b013e328361d178 -
Human Vaccines & Immunotherapeutics Dec 2022Despite recent advances in human immunodeficiency virus-1 (HIV-1) prevention, a fast, safe, and effective vaccine will probably be necessary to end the HIV/AIDS...
BACKGROUND
Despite recent advances in human immunodeficiency virus-1 (HIV-1) prevention, a fast, safe, and effective vaccine will probably be necessary to end the HIV/AIDS pandemic. This study was conducted to evaluate global research trends and map the key bibliometric indices in HIV-1 genetic diversity from 1998 to 2021.
METHODS
A comprehensive online search was conducted in the Web of Science Core Collection database to retrieve published literature on HIV-1 genetic diversity. Key bibliometric indicators were calculated and evaluated using HistCite, Bibliometrix: An R-tool, and VOSviewer software for windows.
RESULTS
A total of 2,060 documents written by 9,201 authors and published in 250 journals were included in the final analysis. Year 2012 was the most productive year with 121 (5.87%) publications. The most prolific author was Shao Yiming (n = 74, 3.59%) from Chinese Center for Disease Control and Prevention. The United States of America was the highly contributing and influential country (n = 681, 33.05%). was the most productive journal (n = 562, 27.2%). Network visualization shows that HIV-1 was the most widely used author keyword.
CONCLUSION
This study provides global research trends and detailed information on HIV-1 genetic diversity. The amount of scientific literature on HIV-1 genetic diversity research has rapidly increased in the last two decades. The maximum number of articles on HIV-1 genetic diversity was published in developed countries; therefore, a scientific research collaboration among researchers and institutes in low-income countries should be promoted and supported.
Topics: AIDS Vaccines; Bibliometrics; Genetic Variation; HIV-1; Humans; Retrospective Studies; United States
PubMed: 35016590
DOI: 10.1080/21645515.2021.2014733 -
Current Opinion in HIV and AIDS Sep 2013We review the broad spectrum of nonreplicating viral vectors which have been studied extensively, from preclinical studies through clinical efficacy trials, and include... (Review)
Review
PURPOSE OF REVIEW
We review the broad spectrum of nonreplicating viral vectors which have been studied extensively, from preclinical studies through clinical efficacy trials, and include some of our most promising HIV vaccine candidates.
RECENT FINDINGS
The success of the RV144 trial, with a canarypox virus-based regimen, contrasts with the failures of the adenovirus-5 (Ad5)-based regimens in the Step study, the Phambili study [HIV Vaccine Trials Network (HVTN) 503], and the HVTN 505 study which was recently modified to halt vaccinations because of clinical futility.
SUMMARY
The safety profile, immunogenicity, and variety of available candidates make the nonreplicating viral vectors attractive in HIV vaccine development. Building from the success of the RV144 study, further studies of Orthopoxvirus-based vaccines, including vaccinia-based vaccines, are ongoing and planned for the future. Despite the failures of the Ad5-based vaccines in clinical efficacy trials, other adenovirus serotypes remain promising candidates, especially in prime-boost combination with other products, and with the potential use of mosaic inserts. Other nonreplicating viral vectors such as the rhabdoviruses, alphaviruses, and the nonhuman adenoviruses, provide additional avenues for exploration.
Topics: AIDS Vaccines; Adenoviridae; Animals; Canarypox virus; Clinical Trials as Topic; Drug Carriers; Drug Evaluation, Preclinical; Genetic Vectors; HIV Infections; Humans; Orthopoxvirus; Treatment Outcome
PubMed: 23925001
DOI: 10.1097/COH.0b013e328363d3b7 -
Antiviral Chemistry & Chemotherapy Sep 2000New combinations of antiretrovirals have improved the quality of life and length of survival of patients with HIV infection and AIDS, but they have significant... (Comparative Study)
Comparative Study Review
New combinations of antiretrovirals have improved the quality of life and length of survival of patients with HIV infection and AIDS, but they have significant disadvantages. These include considerable toxicity, the development of drug resistance and expense. Successful immunotherapeutic vaccination against HIV would overcome these problems. None of the approaches that have been tried so far have shown a sufficient effect on HIV replication or on immunorestoration to merit their introduction to clinical practice. The most developed agent thus far is Remune, a gp120 depleted whole killed HIV-1 vaccine that has shown marked cytotoxic T lymphocyte responses when administered to man. CD4 count and HIV-1 viral load responses have occurred, but have so far been disappointing in their magnitude. Remune is entering Phase III trials in North America, Europe and the Far East, to determine clinical efficacy. Immunization using recombinant HIV envelope proteins, such as rgp160, for example with VaxSyn, have failed to produce a therapeutic response. Similarly, agents using HIV core antigens, such as p24VLP, have also failed to work. Hence, newer strategies have been tried. Recombinant canarypox vaccines like ALVAC 1452 and highly attenuated vaccinia virus vaccines, such as NYVAC, have been used in combination with HIV genes and peptides. Preliminary results suggest that they might reduce the HIV replication rate, but this needs confirming in larger clinical trials. DNA vaccination has produced encouraging results in monkeys, but the success has not yet been repeated in humans. Other strategies at an early stage include the exploitation of the protective alloimmune response in man. Outside the immunotherapeutic area, other promising new strategies that are being developed in parallel, include the fusion inhibitors, such as T-20. The potential benefits from a successful immunotherapeutic vaccine dictate that this area should, and will receive priority.
Topics: AIDS Vaccines; CD4 Lymphocyte Count; Clinical Trials as Topic; HIV Infections; Humans; Immunotherapy; Viral Load
PubMed: 11142629
DOI: 10.1177/095632020001100501 -
Current Opinion in Immunology Aug 2018A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual... (Review)
Review
A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual features and are generated in a fraction of HIV-infected individuals through complex pathways. Current vaccine design approaches seek to trigger rare B cell precursors and then steer affinity maturation toward bnAbs in a multi-stage multi-component immunization approach. These vaccine design strategies have been facilitated by molecular descriptions of bnAb interactions with stabilized HIV trimers, the use of an array of sophisticated approaches for immunogen design, the development of novel animal models for immunogen evaluation and advanced technologies to interrogate antibody responses. In this review, we will discuss leading HIV bnAb vaccine immunogens, immunization strategies and future improvements.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Antibody Affinity; B-Lymphocytes; Disease Models, Animal; HIV Antibodies; HIV Infections; HIV-1; Humans; Lymphocyte Activation; Vaccination
PubMed: 29775847
DOI: 10.1016/j.coi.2018.04.025 -
Expert Review of Proteomics Oct 2017Much of the efforts to develop a vaccine against the human immunodeficiency virus (HIV) have focused on the design of recombinant mimics of the viral attachment... (Review)
Review
Much of the efforts to develop a vaccine against the human immunodeficiency virus (HIV) have focused on the design of recombinant mimics of the viral attachment glycoprotein (Env). The leading immunogens exhibit native-like antigenic properties and are being investigated for their ability to induce broadly neutralizing antibodies (bNAbs). Understanding the relative abundance of glycans at particular glycosylation sites on these immunogens is important as most bNAbs have evolved to recognize or evade the dense coat of glycans that masks much of the protein surface. Understanding the glycan structures on candidate immunogens enables triaging between native-like conformations and immunogens lacking key structural features as steric constraints limit glycan processing. The sensitivity of the processing state of a particular glycan to its structural environment has led to the need for quantitative glycan profiling and site-specific analysis to probe the structural integrity of immunogens. Areas covered: We review analytical methodologies for HIV immunogen evaluation and discuss how these studies have led to a greater understanding of the structural constraints that control the glycosylation state of the HIV attachment and fusion spike. Expert commentary: Total composition and site-specific glycosylation profiling are emerging as standard methods in the evaluation of Env-based immunogen candidates.
Topics: AIDS Vaccines; Glycosylation; Humans; Mass Spectrometry; Polysaccharides; env Gene Products, Human Immunodeficiency Virus
PubMed: 28870097
DOI: 10.1080/14789450.2017.1376658