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BMJ (Clinical Research Ed.) Nov 1990
Topics: Acquired Immunodeficiency Syndrome; Cross Infection; General Surgery; HIV Antibodies; Humans; Occupational Diseases; Risk Assessment; Risk Factors; Surgical Procedures, Operative; United Kingdom
PubMed: 2082964
DOI: 10.1136/bmj.301.6759.1003 -
Advanced Drug Delivery Reviews Aug 2016A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral... (Review)
Review
A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options.
Topics: Antibodies, Neutralizing; HIV Antibodies; HIV Infections; HIV-1; Humans
PubMed: 26827912
DOI: 10.1016/j.addr.2016.01.013 -
Microbiology Spectrum Aug 2014This article focuses on a novel vaccine strategy known as vector-mediated antibody gene transfer, with a particular focus on human immunodeficiency virus (HIV). This... (Review)
Review
This article focuses on a novel vaccine strategy known as vector-mediated antibody gene transfer, with a particular focus on human immunodeficiency virus (HIV). This strategy provides a solution to the problem of current vaccines that fail to generate neutralizing antibodies to prevent HIV-1 infection and AIDS. Antibody gene transfer allows for predetermination of antibody affinity and specificity prior to "immunization" and avoids the need for an active humoral immune response against the HIV envelope protein. This approach uses recombinant adeno-associated viral (rAAV) vectors, which have been shown to transduce muscle with high efficiency and direct the long-term expression of a variety of transgenes, to deliver the gene encoding a broadly neutralizing antibody into the muscle. Following rAAV vector gene delivery, the broadly neutralizing antibodies are endogenously synthesized in myofibers and passively distributed to the circulatory system. This is an improvement over classical passive immunization strategies that administer antibody proteins to the host to provide protection from infection. Vector-mediated gene transfer studies in mice and monkeys with anti-HIV and simian immunodeficiency virus (SIV)-neutralizing antibodies demonstrated long-lasting neutralizing activity in serum with complete protection against intravenous challenge with virulent HIV and SIV. These results indicate that existing potent anti-HIV antibodies can be rapidly moved into the clinic. However, this methodology need not be confined to HIV. The general strategy of vector-mediated antibody gene transfer can be applied to other difficult vaccine targets such as hepatitis C virus, malaria, respiratory syncytial virus, and tuberculosis.
Topics: Adenoviridae; Animals; Antibodies, Neutralizing; Gene Expression; Genetic Vectors; HIV; HIV Antibodies; Haplorhini; Humans; Immunization, Passive; Mice; Recombinant Proteins; Simian Immunodeficiency Virus; Transduction, Genetic
PubMed: 26104192
DOI: 10.1128/microbiolspec.AID-0016-2014 -
Clinical and Vaccine Immunology : CVI Feb 2016Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective... (Review)
Review
Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.
Topics: AIDS Vaccines; Adult; Aging; Antibodies, Neutralizing; Child; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunity, Cellular; Immunity, Humoral; Infant; Vaccination; Vaccines, DNA
PubMed: 26656117
DOI: 10.1128/CVI.00565-15 -
Current HIV/AIDS Reports Oct 2020The application of immunotherapies to HIV presents a new horizon of treatment options, but little is known about what impact they may have on the central nervous system... (Review)
Review
PURPOSE OF REVIEW
The application of immunotherapies to HIV presents a new horizon of treatment options, but little is known about what impact they may have on the central nervous system (CNS). Here we review the most promising immunotherapeutic strategies that can be used to target HIV in the CNS and focus on identifying their potential benefits while exploring the challenges that remain in their application.
RECENT FINDINGS
We have identified five immunotherapeutic strategies that hold potential in managing CNS disease among HIV-infected patients. These include broadly neutralizing antibodies, multi-affinity antibodies, CAR-T cell therapy, checkpoint inhibitors, and therapeutic vaccines. Each class of immunotherapy presents unique mechanisms by which CNS viremia and latency may be addressed but are faced with several challenges. CAR-T cell therapy and multi-affinity antibodies seem to hold promise, but combination therapy is likely to be most effective. However, more human trials are needed before the clinical benefits of these therapies are realized.
Topics: Antibodies, Neutralizing; Central Nervous System; Combined Modality Therapy; HIV Antibodies; HIV Infections; Humans; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Viral Vaccines; Viremia
PubMed: 32671567
DOI: 10.1007/s11904-020-00519-w -
Cell Feb 2014Despite 30 years of effort, there is no effective vaccine for HIV-1. However, antibodies can prevent HIV-1 infection in humanized mice and macaques when passively... (Review)
Review
Despite 30 years of effort, there is no effective vaccine for HIV-1. However, antibodies can prevent HIV-1 infection in humanized mice and macaques when passively transferred. New single-cell-based methods have uncovered many broad and potent donor-derived antibodies, and structural studies have revealed the molecular bases for their activities. The new data suggest why such antibodies are difficult to elicit and inform HIV-1 vaccine development efforts. In addition to protecting against infection, the newly identified antibodies can suppress active infections in mice and macaques, suggesting they could be valuable additions to anti-HIV-1 therapies and to strategies to eradicate HIV-1 infection.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunotherapy; env Gene Products, Human Immunodeficiency Virus
PubMed: 24529371
DOI: 10.1016/j.cell.2014.01.052 -
Frontiers in Immunology 2023Glycan masking is a novel technique in reverse vaccinology in which sugar chains (glycans) are added on the surface of immunogen candidates to hide regions of low... (Review)
Review
Glycan masking is a novel technique in reverse vaccinology in which sugar chains (glycans) are added on the surface of immunogen candidates to hide regions of low interest and thus focus the immune system on highly therapeutic epitopes. This shielding strategy is inspired by viruses such as influenza and HIV, which are able to escape the immune system by incorporating additional glycosylation and preventing the binding of therapeutic antibodies. Interestingly, the glycan masking technique is mainly used in vaccine design to fight the same viruses that naturally use glycans to evade the immune system. In this review we report the major successes obtained with the glycan masking technique in epitope-focused vaccine design. We focus on the choice of the target antigen, the strategy for immunogen design and the relevance of the carrier vector to induce a strong immune response. Moreover, we will elucidate the different applications that can be accomplished with glycan masking, such as shifting the immune response from hyper-variable epitopes to more conserved ones, focusing the response on known therapeutic epitopes, broadening the response to different viral strains/sub-types and altering the antigen immunogenicity to elicit higher or lower immune response, as desired.
Topics: HIV Antibodies; Antibodies, Neutralizing; Epitopes; Polysaccharides; HIV-1
PubMed: 37033915
DOI: 10.3389/fimmu.2023.1126034 -
Genes and Immunity Aug 2022The development of an effective vaccine against HIV is desperately needed. The successive failures of HIV vaccine efficacy trials in recent decades have shown the... (Review)
Review
The development of an effective vaccine against HIV is desperately needed. The successive failures of HIV vaccine efficacy trials in recent decades have shown the difficulty of inducing an appropriate protective immune response to fight HIV. Different correlates of antibody parameters associated with a decreased risk of HIV-1 acquisition have been identified. However, these parameters are difficult to reproduce and improve, possibly because they have an intricate and combined action. Here, we describe the numerous antibody (Ab) functions associated with HIV-1 protection and report the interrelated parameters regulating their complex functions. Indeed, besides neutralizing and Fc-mediated activity, additional factors such as Ab type, concentration and kinetics of induction, and Fc-receptor expression and binding capacity also influence the protective effect conferred by Abs. As these parameters were described to be associated with ethnicity, age and sex, these additional factors must be considered for the development of an effective immune response. Therefore, future vaccine designs need to consider these multifaceted Ab functions together with the demographic attributes of the patient populations.
Topics: AIDS Vaccines; Antibodies, Neutralizing; Antibody Formation; HIV Antibodies; HIV Infections; HIV-1; Humans; Receptors, Fc; Vaccination
PubMed: 35688931
DOI: 10.1038/s41435-022-00175-7 -
Autoimmunity Reviews Jun 2008Immunoglobulins (Igs) in uninfected humans recognize residues 421-433 located in the B cell superantigenic site (SAg) of the HIV envelope protein gp120 and catalyze its... (Review)
Review
Immunoglobulins (Igs) in uninfected humans recognize residues 421-433 located in the B cell superantigenic site (SAg) of the HIV envelope protein gp120 and catalyze its hydrolysis by a serine protease-like mechanism. The catalytic activity is encoded by germline Ig variable (V) region genes, and is expressed at robust levels by IgMs and IgAs but poorly by IgGs. Mucosal IgAs are highly catalytic and neutralize HIV, suggesting that they constitute a first line of defense against HIV. Lupus patients produce the Igs at enhanced levels. Homology of the 421-433 region with an endogenous retroviral sequence and a bacterial protein may provide clues about the antigen driving anti-SAg synthesis in lupus patients and uninfected subjects. The potency and breadth of HIV neutralization revives hopes of clinical application of catalytic anti-421-433 Igs as immunotherapeutic and topical microbicide reagents. Adaptive improvement of anti-SAg catalytic Igs in HIV infected subjects is not customary. Further study of the properties of the naturally occurring anti-SAg catalytic Igs should provide valuable guidance in designing a prophylactic vaccine that amplifies protective catalytic immunity to HIV.
Topics: Antibodies, Catalytic; Evolution, Molecular; HIV Antibodies; HIV Envelope Protein gp120; HIV-1; Humans; Superantigens
PubMed: 18558365
DOI: 10.1016/j.autrev.2008.04.002 -
Retrovirology Jul 2018A central puzzle in HIV-1 research is the inability of vaccination or even infection to reliably elicit humoral responses against broadly neutralizing epitopes in the... (Review)
Review
A central puzzle in HIV-1 research is the inability of vaccination or even infection to reliably elicit humoral responses against broadly neutralizing epitopes in the HIV-1 envelope protein. In infected individuals, broadly neutralizing antibodies (bNAbs) do arise in a substantial minority, but only after 2 or more years of chronic infection. All known bNAbs possess at least one of three traits: a high frequency of somatic hypermutation, a long third complementarity determining region in the antibody heavy chain (HCDR3), or significant poly- or autoreactivity. Collectively, these observations suggest a plausible explanation for the rarity of many types of bNAbs: namely, that their generation is blocked by immunological tolerance or immune response checkpoints, thereby mandating that B cells take a tortuous path of somatic evolution over several years to achieve broadly neutralizing activity. In this brief review, we discuss the evidence for this tolerance hypothesis, its implications for HIV-1 vaccine design, and potential ways to access normally forbidden compartments of the antibody repertoire by modulating or circumventing tolerance controls.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Antibody Specificity; B-Lymphocytes; HIV Antibodies; HIV Infections; HIV-1; Humans; Immune Tolerance
PubMed: 30055635
DOI: 10.1186/s12977-018-0435-0