Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 31, 2025

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements our understanding HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines mRNA technology induce broadly neutralizing antibodies, have shown promise. However, efficacy these modest, with best results achieving approximately 30% effectiveness. Ongoing research emphasizes necessity multifaceted strategy overcome obstacles achieve breakthrough development. This review summarizes current approaches utilized further understand create global vaccine. We discuss impact on for other diseases, COVID-19, influenza, Zika virus. Additionally, we highlight specific limitations faced each approach present methods researchers employ challenges. These techniques, which demonstrated preclinical clinical success, advanced field closer ultimate goal developing Leveraging will enable strides combating infectious ultimately improving health outcomes.

Language: Английский

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mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models

Science Immunology, Journal Year: 2024, Volume and Issue: 9(95)

Published: May 10, 2024

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) the CD4-binding site of HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as soluble self-assembling nanoparticle mouse models. In model with three humanized B cell lineages bearing distinct VRC01-precursor receptors (BCRs) similar affinities for eOD-GT8, all could be simultaneously primed and undergo diversification affinity maturation without exclusionary competition. Boosts drove precursor participation germinal centers; accumulation somatic hypermutations, including key positions; boost native-like antigens two lineages. We prime-boost regimen nanoparticles encoded by mRNA-LNP, demonstrating that multiple can primed, boosted, diversified along bnAb pathway.

Language: Английский

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Interventions during Early Infection: Opening a Window for an HIV Cure?

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1588 - 1588

Published: Oct. 9, 2024

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure remained elusive. Elimination latent reservoirs that persist throughout infection is most challenging barrier to cure. The progressive marked by increasing size and diversity until effective immune response mobilized, which can control but not eliminate infection. stalemate between replication manifested establishment viral set point. ART initiation during early stage limits reservoir development, preserves function, improves quality life, may lead ART-free remission in few people living with (PLWH). However, overwhelming majority PLWH, alone does HIV, lifelong needed sustain suppression. A critical area research focused on determining whether could be functionally cured if additional treatments are provided alongside ART. Several interventions including Block Lock, Shock Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell gene have demonstrated delayed rebound and/or animal models some PLWH. Whether or their application improve success less studied. Herein, we review current state clinical investigative discuss potential likelihood post-treatment initiated

Language: Английский

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The Fight Continues: Virus Without Vaccines

Published: Jan. 1, 2025

Language: Английский

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Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans

Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by series of heterologous boosters elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States IAVI-G003 Rwanda South Africa, we evaluated safety immunogenicity mRNA-encoded nanoparticles as immunogens (both trials) first-boosting (IAVI-G002). The vaccines were generally safe well tolerated, except 18% participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies SHM, boosting elicited increased affinity, neutralization activity toward development. results establish proof concept that can advance bnAb-precursor maturation demonstrate Africa where burden is highest.

Language: Английский

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Advancing Human Vaccine Development Using Humanized Mouse Models

Vaccines, Journal Year: 2024, Volume and Issue: 12(9), P. 1012 - 1012

Published: Sept. 4, 2024

The development of effective vaccines against infectious diseases remains a critical challenge in global health. Animal models play crucial role vaccine by providing valuable insights into the efficacy, safety, and mechanisms immune response induction, which guide design formulation vaccines. However, traditional animal often inadequately recapitulate human responses. Humanized mice (hu-mice) with functional system have emerged as invaluable tools bridging translational gap between preclinical research clinical trials for development. This review summarizes commonly used hu-mice advances optimizing them to improve We application humanized focus on HIV-1 also discuss remaining challenges improvements needed currently available better facilitate testing diseases.

Language: Английский

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mRNA Vaccines for HIV‐1

Published: Dec. 6, 2024

The development of a protective vaccine for HIV-1 represents one the most formidable challenges modern science. Despite long series failures over past 40 years, accruing evidence indicates that an is feasible. recent encounter between field and messenger RNA (mRNA) technology has opened new perspectives to accelerate discovery. extraordinary efficiency versatility mRNA, coupled with its ability induce endogenous expression bona fide native envelope trimers, offer specific benefits vaccine, as confirmed by results preclinical studies.

Language: Английский

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Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Aug. 21, 2024

Abstract Human immunodeficiency virus type 1 (HIV-1) vaccine immunogens capable of inducing broadly neutralizing antibodies (bNAbs) remain obscure. HIV-1 evades immune responses through enormous diversity and hides its conserved vulnerable epitopes on the envelope glycoprotein (Env) by displaying an extensive immunodominant glycan shield. In elite viremic controllers, glycan-dependent bNAbs targeting Env have been isolated are utilized as design templates. However, immunological tolerance mechanisms limit development these in general population. The well characterized monoclonal variants frequently exhibit levels somatic hypermutation, a long third heavy chain complementary determining region, or short light complementarity some poly-reactivity to autoantigens. This review elaborates obstacles engaging manipulating effective immunogen describes alternative reverse vaccinology approach develop novel category bNAb-epitope-derived non-cognate for design. Graphical

Language: Английский

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