☆ 4.2 Review

Divide and conquer: broadly neutralizing antibody combinations for improved HIV-1 viral coverage

CURRENT OPINION IN HIV AND AIDS (2023)

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Article Medicine, Research & Experimental

Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency

Baoshan Zhang et al.

Summary: Antibody CAP256-VRC26.25 targets the second hypervariable region (V2) with extraordinary neutralization potency, but limited breadth. By linking CAP256V2LS to the llama nanobody J3, the bispecific antibody exhibited improved breadth and potency through synergistic neutralization.

MABS (2023)

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Review Immunology

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies

Barton F. Haynes et al.

Summary: The development of a safe and effective HIV-1 vaccine has been a challenging task due to the genetic diversity of the virus and its mechanisms of immune evasion. This article discusses strategies for inducing potent and broad HIV-1 neutralizing antibodies and outlines the necessary steps for achieving ultimate success.

NATURE REVIEWS IMMUNOLOGY (2023)

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Article Cell Biology

Potent anti-viral activity of a trispecific HIV neutralizing antibody in SHIV-infected monkeys

Amarendra Pegu et al.

Summary: The use of trispecific bNAbs can effectively reduce viremia and maintain low levels of virus in the body through immune control. Compared to single bNAbs, trispecific bNAbs can suppress the emergence of resistance and minimize the potential for immune escape.

CELL REPORTS (2022)

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Article Multidisciplinary Sciences

Combination anti-HIV antibodies provide sustained virological suppression

Michael C. Sneller et al.

Summary: The combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV. This study offers guidance for future clinical trials involving next-generation antibodies with long half-lives.

NATURE (2022)

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Article Multidisciplinary Sciences

Prolonged viral suppression with anti-HIV-1 antibody therapy

Christian Gaebler et al.

Summary: Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells. A clinical study showed that 76% of HIV-infected individuals who received a combination of antibodies maintained virologic suppression for at least 20 weeks without antiretroviral therapy. The administration of antibodies affected the HIV-1 reservoir, but further research is needed to define the precise effect of antibody immunotherapy.

NATURE (2022)

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Article Biochemistry & Molecular Biology

Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial

Boris Julg et al.

Summary: HIV-1 therapy with single or dual broadly neutralizing antibodies has shown viral escape, indicating the need for triple or more bNAb therapy. Results from human trials suggest that a combination of broad antiviral activity and high serum concentrations is necessary for viral control.

NATURE MEDICINE (2022)

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Article Virology

Broadly neutralizing antibodies against HIV-1 and concepts for application

Henning Gruell et al.

Summary: Potent broadly neutralizing antibodies (bNAbs) targeting HIV-1 have shown significant antiviral activity, but their effectiveness on the latent reservoir remains limited.

CURRENT OPINION IN VIROLOGY (2022)

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Article Biology

Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1

Colin LaMont et al.

Summary: This study proposes a computational approach based on the population genetics of HIV escape to predict the efficacy of bNAb therapy. By using high-throughput HIV sequence data from bNAb-naive patients to parametrize HIV escape, the distribution of rebound times in three clinical trials is predicted. It is shown that a combination of three bNAbs is necessary to effectively suppress viral escape.

ELIFE (2022)

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Article Biochemistry & Molecular Biology

Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition

Peter B. Gilbert et al.

Summary: By integrating serum concentration and in vitro inhibitory concentration, the PT80 biomarker can guide the effective prevention of HIV-1 acquisition. The PT80 biomarker can be used to predict HIV-1 prevention efficacy and is proposed as a tool for evaluating bNAb regimens and candidate vaccines.

NATURE MEDICINE (2022)

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Review Immunology

A calculated risk: Evaluating HIV resistance to the broadly neutralising antibodies10-1074 and 3BNC117

Panagiota Zacharopoulou et al.

Summary: Broadly neutralising antibodies (bNAbs) are a promising new therapy for HIV infection, but their effective use is impacted by viral resistance and the potential for developing new resistance during treatment. Clinical trials of bNAbs 10-1074 and 3BNC117 have shown viral mutations leading to bNAb resistance, highlighting the need for predicting sensitivity to reduce treatment failure risk.

CURRENT OPINION IN HIV AND AIDS (2022)

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Article Multidisciplinary Sciences

Engineering pan-HIV-1 neutralization potency through multispecific antibody avidity

Edurne Rujas et al.

Summary: In this study, HIV-1 bNAbs were engineered by directly fusing their Fab fragments to the human apoferritin light chain, resulting in a multispecific and avid molecule. The molecule exhibited high neutralization potency against a broad panel of HIV-1 pseudoviruses and demonstrated IgG-like bioavailability in vivo through Fc receptor modulation.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Medicine, General & Internal

Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials

Yunda Huang et al.

Summary: The study examines the pharmacokinetics and neutralization coverage of VRC01 antibody in different cohorts to determine its effectiveness in preventing HIV-1 infection. Results suggest that differences in body weight and gender may impact the pharmacokinetics of VRC01. The study provides insights into interpreting the AMP trial results and investigating the correlation between VRC01 concentration, neutralization, and HIV incidence.

EBIOMEDICINE (2021)

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Article Medicine, General & Internal

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition

L. Corey et al.

Summary: The study found that broadly neutralizing antibodies did not prevent HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates indicated that prophylaxis with broadly neutralizing antibodies may be effective.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Immunology

Broadly Neutralizing Antibodies for HIV-1 Prevention

Stephen R. Walsh et al.

Summary: The current clinical studies are actively exploring the use of bnAbs as passive immunization strategies to prevent HIV-1 infection. Recent trials have shown that bnAbs can provide protection against HIV-1 infection in humans, but there are still significant barriers to overcome.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Immunology

Broadly neutralizing antibodies for the treatment and prevention of HIV infection

Marina Caskey

CURRENT OPINION IN HIV AND AIDS (2020)

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Review Immunology

Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention

Kathryn E. Stephenson et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 38 (2020)

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Article Microbiology

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design

Christine A. Bricault et al.

CELL HOST & MICROBE (2019)

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Review Immunology

Broadly neutralizing antibodies for treatment and prevention of HIV-1 infection

Yehuda Z. Cohen et al.

CURRENT OPINION IN HIV AND AIDS (2018)

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Article Microbiology

Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections

Kshitij Wagh et al.

PLOS PATHOGENS (2018)

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Article Biochemistry & Molecular Biology

Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals

Yotam Bar-On et al.

NATURE MEDICINE (2018)

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Review Immunology

Identification and specificity of broadly neutralizing antibodies against HIV

Laura E. McCoy et al.

IMMUNOLOGICAL REVIEWS (2017)

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Article Multidisciplinary Sciences

Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques

Ling Xu et al.

SCIENCE (2017)

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Article Biochemistry & Molecular Biology

Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity

Yaoxing Huang et al.

CELL (2016)

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Article Microbiology

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort

Elise Landais et al.

PLOS PATHOGENS (2016)

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Article Microbiology

Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C

Kshitij Wagh et al.

PLOS PATHOGENS (2016)

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Article Microbiology

Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies

Laura E. McCoy et al.

PLOS PATHOGENS (2015)

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