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寻找基于抗体的 HIV 疫苗。

The quest for an antibody-based HIV vaccine.

机构信息

Duke Human Vaccine Institute, Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC, USA.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

出版信息

Immunol Rev. 2017 Jan;275(1):5-10. doi: 10.1111/imr.12517.


DOI:10.1111/imr.12517
PMID:28133795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5384259/
Abstract

Despite major advances in our understanding of the biology of HIV-1 infection, and advances in antiretroviral therapy to treat the disease, there were 2.1 million new cases of HIV-1 infection in 2015, and 36.7 million people living with AIDS (http://www.unaids.org/en/resources/fact-sheet). Thus, a vaccine that can prevent HIV-infection remains a global priority. Thirty-three years after the discovery of HIV-1(1), and the demonstration it was the cause of AIDS(2) and after 6 HIV-1 vaccine efficacy trials (–8), no HIV-1 candidate vaccine has shown enough efficacy to be approved for clinical use. Of several vaccine concepts tested in efficacy trials, only one, the RV144 pox virus prime, protein boost (ALVAC/AIDSVAX B/E) vaccine, showed a low level of vaccine protection with an estimated 31% vaccine efficacy (8). Candidate vaccines have sought to elicit both antibody and T-cell responses, but to fully prevent the acquisition of infection, a major focus has been on the induction of protective antibody responses (9, 10). Hence, the focus of this issue of is “Antibodies and Immunity to HIV”. Animal models have demonstrated that passive administration of HIV-1-- neutralizing antibodies can fully protect against infection, but the induction of such antibodies via immunization remains a major scientific challenge. With recent advances in the isolation and characterization of broadly neutralizing antibodies (bnAbs) from HIV-1-infected subjects, in elucidating structures of the HIV-1 envelope glycoprotein (Env), in defining novel approaches to immunogen design, and in improved understanding of the immunological pathways leading to bNAb elicitation, the challenge developing an HIV-1 vaccine appears to be more tractable. The articles in this issue highlight both major areas of HIV-1 vaccine development progress and remaining obstacles, and provide context for the renewed optimism that a highly effective vaccine, while not imminent, is possible.

摘要

尽管我们对 HIV-1 感染的生物学有了重大的认识进展,也有了抗逆转录病毒疗法来治疗这种疾病,但 2015 年仍有 210 万例新的 HIV-1 感染病例,有 3670 万人患有艾滋病(http://www.unaids.org/en/resources/fact-sheet)。因此,预防 HIV 感染的疫苗仍然是全球的重点。在发现 HIV-1 33 年之后(1),并证明它是艾滋病的病因(2),以及在进行了 6 次 HIV-1 疫苗功效试验(–8)之后,没有一种 HIV-1 候选疫苗显示出足够的功效被批准用于临床使用。在功效试验中测试了几种疫苗概念,只有一种疫苗,即 RV144 痘病毒初免-蛋白加强(ALVAC/AIDSVAX B/E)疫苗,显示出低水平的疫苗保护效果,估计疫苗有效率为 31%(8)。候选疫苗试图引发抗体和 T 细胞反应,但为了充分防止感染,主要重点是诱导保护性抗体反应(9,10)。因此,本期的重点是“HIV 的抗体和免疫”。动物模型表明,被动给予 HIV-1 中和抗体可以完全预防感染,但通过免疫接种诱导这种抗体仍然是一个主要的科学挑战。随着最近从 HIV-1 感染的受者中分离和鉴定出广泛中和抗体(bnAbs)的进展,阐明 HIV-1 包膜糖蛋白(Env)的结构,定义新的免疫原设计方法,以及对导致 bnAb 产生的免疫途径的理解的提高,开发 HIV-1 疫苗的挑战似乎更加可行。本期的文章突出了 HIV-1 疫苗开发进展的两个主要领域和仍然存在的障碍,并为重新乐观地认为一种高效疫苗虽然不是迫在眉睫,但有可能实现提供了背景。

相似文献

[1]
The quest for an antibody-based HIV vaccine.

Immunol Rev. 2017-1

[2]
In vivo protection by broadly neutralizing HIV antibodies.

Trends Microbiol. 2014-8-26

[3]
HIV Vaccines: One Step Closer.

Trends Mol Med. 2016-11-23

[4]
A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques.

J Virol. 2018-2-12

[5]
Toward an HIV type 1 vaccine that generates potent, broadly cross-reactive neutralizing antibodies.

AIDS Res Hum Retroviruses. 1999-5-20

[6]
HIV vaccine development--improving on natural immunity.

N Engl J Med. 2011-9-8

[7]
The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens.

Science. 1998-6-19

[8]
Regulatory T cell abundance and activation status before and after priming with HIVIS-DNA and boosting with MVA-HIV/rgp140/GLA-AF may impact the magnitude of the vaccine-induced immune responses.

Immunobiology. 2018-12

[9]
Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses.

J Virol. 2022-1-12

[10]
Immunology. Close to the edge: neutralizing the HIV-1 envelope.

Science. 2005-6-24

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Transient regulatory T cell manipulation is limited by anti-antibody responses in HIV-1 envelope immunized rhesus macaques.

iScience. 2025-7-23

[2]
Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response.

Nat Commun. 2025-6-3

[3]
A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.

Structure. 2025-7-3

[4]
Rational design of next-generation filovirus vaccines with glycoprotein stabilization, nanoparticle display, and glycan modification.

bioRxiv. 2025-3-2

[5]
Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.

Vaccines (Basel). 2025-1-14

[6]
A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

Front Immunol. 2024

[7]
Prediction of differential Gag versus Env responses to a mosaic HIV-1 vaccine regimen by HLA class I alleles.

J Virol. 2024-8-20

[8]
A branching stochastic evolutionary model of the B-cell repertoire.

J Math Biol. 2024-6-7

[9]
Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS.

JCI Insight. 2024-4-8

[10]
Potency and durability of T and B cell immune responses after homologous and heterologous vector delivery of a trimer-stabilized, membrane-displayed HIV-1 clade ConC Env protein.

Front Immunol. 2023

本文引用的文献

[1]
Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies.

Sci Immunol. 2016-7-29

[2]
Identification and specificity of broadly neutralizing antibodies against HIV.

Immunol Rev. 2017-1

[3]
The HIV-1 envelope glycoprotein structure: nailing down a moving target.

Immunol Rev. 2017-1

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Antibodyomics: bioinformatics technologies for understanding B-cell immunity to HIV-1.

Immunol Rev. 2017-1

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Complex immune correlates of protection in HIV-1 vaccine efficacy trials.

Immunol Rev. 2017-1

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Systems serology for evaluation of HIV vaccine trials.

Immunol Rev. 2017-1

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Antibody gene transfer with adeno-associated viral vectors as a method for HIV prevention.

Immunol Rev. 2017-1

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Host controls of HIV broadly neutralizing antibody development.

Immunol Rev. 2017-1

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Native-like Env trimers as a platform for HIV-1 vaccine design.

Immunol Rev. 2017-1

[10]
Evolution of B cell analysis and Env trimer redesign.

Immunol Rev. 2017-1

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