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Related Experiment Video

Updated: Jan 6, 2026

Oral Combinational Antiretroviral Treatment in HIV-1 Infected Humanized Mice
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Triple rAAV9 Vector Combinations Encoding Broadly Neutralizing Antibodies Effectively Suppress HIV-1 Infection in

Danila S Leontyev1, Felix A Urusov1, Dina V Glazkova1

  • 1Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia.

International Journal of Molecular Sciences
|November 27, 2025
PubMed
Summary

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Two novel antibody combinations, CombiMab-1 and CombiMab-2, delivered via recombinant adeno-associated virus serotype 9 vectors, effectively protected humanized mice from HIV-1 challenge, preventing viremia and preserving CD4+ T-lymphocyte counts.

Area of Science:

  • Immunology
  • Virology
  • Gene Therapy

Background:

  • Human Immunodeficiency Virus (HIV) remains a global health challenge.
  • Developing effective and durable HIV-1 prevention strategies is critical.
  • Gene therapy offers a novel approach for delivering therapeutic antibodies.

Purpose of the Study:

  • To evaluate the protective efficacy of two distinct combinations of broadly neutralizing antibodies against HIV-1.
  • To assess the ability of recombinant adeno-associated virus serotype 9 (rAAV9) vectors to deliver these antibodies.
  • To determine the impact of antibody treatment on viral load and CD4+ T-lymphocyte counts in a humanized mouse model.

Main Methods:

  • Humanized mice were established with primary CD4+ T-lymphocytes.
  • Mice received preventive treatment with rAAV9 vectors encoding CombiMab-1 or CombiMab-2.
Keywords:
10-107410E8AAV vectorsCD4+ T-lymphocytesCombiMab-1CombiMab-2HIV-1N6PGDM1400VRC07-523broadly neutralizing antibodieshumanized micepassive immunizationviral load

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  • Animals were subsequently challenged with HIV-1.
  • Viral load (viremia) and CD4+ T-lymphocyte counts were monitored.
  • Main Results:

    • Mice treated with CombiMab-1 or CombiMab-2 showed no detectable viremia post-challenge.
    • Preventive treatment maintained human CD4+ T-lymphocyte counts in treated mice.
    • Control animals developed viremia and experienced a decline in CD4+ T-lymphocyte counts.

    Conclusions:

    • CombiMab-1 and CombiMab-2 delivered via rAAV9 vectors demonstrate significant protective efficacy against HIV-1 challenge.
    • This gene therapy approach offers a promising strategy for HIV-1 prevention.
    • The study highlights the potential of broadly neutralizing antibodies for long-term HIV-1 control.