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International Journal of Molecular... Apr 2018Since the identification of the Human Immunodeficiency Virus type 1 (HIV-1) as the etiologic agent of AIDS (Acquired Immunodeficiency Syndrome), many efforts have been... (Review)
Review
Since the identification of the Human Immunodeficiency Virus type 1 (HIV-1) as the etiologic agent of AIDS (Acquired Immunodeficiency Syndrome), many efforts have been made to stop the AIDS pandemic. A major success of medical research has been the development of the highly active antiretroviral therapy and its availability to an increasing number of people worldwide, with a considerable effect on survival. However, a safe and effective vaccine able to prevent and eradicate the HIV pandemic is still lacking. Clinical trials and preclinical proof-of-concept studies in nonhuman primate (NHP) models have provided insights into potential correlates of protection against the HIV-1 infection, which include broadly neutralizing antibodies (bnAbs), non-neutralizing antibodies targeting the variable loops 1 and 2 (V1V2) regions of the HIV-1 envelope (Env), polyfunctional antibody, and Env-specific T-cell responses. In this review, we provide a brief overview of different HIV-1 vaccine approaches and discuss the current understanding of the cellular and humoral correlates of HIV-1 immunity.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Clinical Trials as Topic; HIV Antibodies; HIV Infections; HIV-1; Humans; env Gene Products, Human Immunodeficiency Virus
PubMed: 29671786
DOI: 10.3390/ijms19041241 -
The Pan African Medical Journal 2015More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The... (Review)
Review
More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa.
Topics: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Africa South of the Sahara; HIV Infections; Humans; Public Health
PubMed: 26185576
DOI: 10.11604/pamj.2015.20.386.4660 -
Journal of Immunology Research 2015HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate... (Review)
Review
HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines.
Topics: AIDS Vaccines; Antibodies, Neutralizing; CD8-Positive T-Lymphocytes; Clinical Trials as Topic; Genetic Vectors; HIV Antibodies; HIV Infections; Humans; Vaccines, DNA
PubMed: 26579546
DOI: 10.1155/2015/560347 -
Current Opinion in Virology Apr 2016Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Non-efficacious preventative vaccine approaches include bivalent recombinant gp120... (Review)
Review
Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Non-efficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials.
Topics: AIDS Vaccines; Antibodies, Monoclonal; Clinical Trials as Topic; Genetic Vectors; HIV; HIV Envelope Protein gp120; HIV Infections; Humans; Immunization, Passive; Vaccination; Vaccines, DNA; Viral Load; tat Gene Products, Human Immunodeficiency Virus
PubMed: 26985884
DOI: 10.1016/j.coviro.2016.02.010 -
Nature Immunology Nov 2018In this Review, we highlight some recent developments in the discovery and application of broadly neutralizing antibodies (bnAbs) to human immunodeficiency virus (HIV);... (Review)
Review
In this Review, we highlight some recent developments in the discovery and application of broadly neutralizing antibodies (bnAbs) to human immunodeficiency virus (HIV); i.e., antibodies able to neutralize diverse isolates of HIV. We consider the characterization of novel bnAbs, recent data on the effects of bnAbs in vivo in humans and animal models, and the importance of both kinds of data for the application of Abs to prophylaxis and therapy and to guide vaccine design. We seek to place newly discovered bnAbs in the context of existing bnAbs, and we explore the various characteristics of the antibodies that are most desirable for different applications.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; HIV Antibodies; HIV Infections; Humans
PubMed: 30333615
DOI: 10.1038/s41590-018-0235-7 -
Current Opinion in HIV and AIDS Jul 2024Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy... (Review)
Review
PURPOSE OF REVIEW
Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies.
RECENT FINDINGS
During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials.
SUMMARY
Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.
Topics: Humans; HIV Infections; Immunotherapy; Animals; Child; Macaca mulatta; Disease Models, Animal; Infant; Simian Immunodeficiency Virus; AIDS Vaccines
PubMed: 38841850
DOI: 10.1097/COH.0000000000000857 -
AIDS Reviews Oct 2022Although highly active antiretroviral therapy has transformed HIV-1 infection into a manageable chronic disease, the development of an effective vaccine is still an... (Review)
Review
Although highly active antiretroviral therapy has transformed HIV-1 infection into a manageable chronic disease, the development of an effective vaccine is still an important and challengeable research field of HIV-1 treatment. The challenge arises from an enormous diversity of HIV-1 strains and their rapid evolution ahead of effective immune responses. HIV-1 evasion from host immunity contributes to viral spread and pathogenesis, thus understanding the mechanisms of HIV-1 immune evasion is important. In this review, we summarized our present knowledge on the mechanisms how HIV-1 escapes immune responses. Such knowledge will help with the design of effective vaccines capable of inducing immune control of HIV-1.
Topics: Humans; HIV-1; HIV Infections; HIV Seropositivity; Immune Evasion; AIDS Vaccines; Antibodies, Neutralizing
PubMed: 35504029
DOI: 10.24875/AIDSRev.21000068 -
Journal of Immunology Research 2015Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is a worldwide epidemic, with over 35 million people infected currently. Therefore, the... (Review)
Review
Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is a worldwide epidemic, with over 35 million people infected currently. Therefore, the development of a safe and effective HIV-1 vaccine is on top of the global health priority. In the past few years, there have been many promising advances in the prevention of HIV/AIDS, among which the RV144 Thai trial has been encouraging and suggests optimization of the current vaccine strategies or search for novel strategies. Here we reviewed the brief history of HIV-1 vaccine, analyzed key challenges existing now, and illustrated future research priority/directions for a therapeutic or prophylactic HIV-1 vaccine, with the hope of accelerating the speed of vaccine development. We believe that an effective HIV-1 vaccine, together with other prevention approaches, will bring an end to this epidemic in the near future.
Topics: AIDS Vaccines; Animals; HIV Infections; Humans; Research
PubMed: 25861656
DOI: 10.1155/2015/503978 -
Nanomedicine (London, England) Mar 2017The development of a successful vaccine against HIV is a major global challenge. Antiretroviral therapy is the standard treatment against HIV-1 infection. However, only... (Review)
Review
The development of a successful vaccine against HIV is a major global challenge. Antiretroviral therapy is the standard treatment against HIV-1 infection. However, only 46% of the eligible people received the therapy in 2015. Furthermore, suboptimal adherence poses additional obstacles. Therefore, there is an urgent need for an HIV-1 vaccine. The most promising clinical trial to date is Phase III RV144, which for the first time demonstrated the feasibility of vaccine-mediated immune protection against HIV-1. Nevertheless, its 31% efficacy and limited durability underscore major hurdles. Here, we discuss recent progress in HIV-1 vaccine development with a special emphasis on nanovaccines, which are at the forefront of efforts to develop a successful HIV-1 vaccine.
Topics: AIDS Vaccines; HIV Infections; HIV-1; Humans; Nanoparticles
PubMed: 28244816
DOI: 10.2217/nnm-2016-0381 -
Expert Opinion on Biological Therapy 2015Classical approaches aimed at targeting the HIV-1 envelope as well as other structural viral proteins have largely failed. The HIV-1 transactivator of transcription... (Review)
Review
INTRODUCTION
Classical approaches aimed at targeting the HIV-1 envelope as well as other structural viral proteins have largely failed. The HIV-1 transactivator of transcription (Tat) is a key HIV virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. Notably, anti-Tat Abs are uncommon in natural infection and, when present, correlate with the asymptomatic state and lead to lower or no disease progression. Hence, targeting Tat represents a pathogenesis-driven intervention.
AREAS COVERED
Here, we review the rationale and the translational development of a therapeutic vaccine targeting the Tat protein. Preclinical and Phase I studies, Phase II trials with Tat in anti-Tat Ab-negative, virologically suppressed highly active antiretroviral therapy-treated subjects in Italy and South Africa were conducted. The results indicate that Tat-induced immune responses are necessary to restore immune homeostasis, to block the replenishment and to reduce the size of the viral reservoir. Additionally, they may help in establishing key parameters for highly active antiretroviral therapy intensification and a functional cure.
EXPERT OPINION
We propose the therapeutic setting as the most feasible to speed up the testing and comparison of preventative vaccine candidates, as the distinction lies in the use of the vaccine in uninfected versus infected subjects and not in the vaccine formulation.
Topics: AIDS Vaccines; Animals; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Disease Progression; HIV Infections; HIV-1; Humans; tat Gene Products, Human Immunodeficiency Virus
PubMed: 26096836
DOI: 10.1517/14712598.2015.1021328