ArticleProceedings of the National Academy of Sciences of the United States of America2015
Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 95 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed.
- Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.Vaccine · 2021Trial
- Vaccine-Induced Antibodies Mediate Higher Antibody-Dependent Cellular Cytotoxicity After Interleukin-15 Pretreatment of Natural Killer Effector Cells.Frontiers in immunology · 2019Trial
- Rapid and robust immune response boosting with potent, next-generation adjuvant in viral vector-primed primates.Journal of virology · 2026Article
- Effects and mechanisms of monoclonal and polyclonal human antibodies in protection of humanized mice from HIV-1 challenge.bioRxiv : the preprint server for biology · 2025Article
- Induction of HIV-1-specific antibody-mediated effector functions by native-like envelope trimers in humans.PLoS pathogens · 2025Article
- Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.PLoS pathogens · 2024Article
- Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response.Nature communications · 2024Article
- Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV-workshop report.NPJ vaccines · 2024Article
- Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells.NPJ vaccines · 2023Article
- Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.PLoS pathogens · 2023Article
- Peripheral Mononuclear Cells Surface Markers Evaluation in Different Stages of Hepatocellular Carcinoma; in a Trial for Early and Accurate Diagnosis in Patients with Post-Hepatitis Liver Cirrhosis and Unremarkable Raised AFP.International journal of general medicine · 2023Article
- Complementary Presence of HBV Humoral and T-cell Response Provides Protective Immunity after Neonatal Immunization.Journal of clinical and translational hepatology · 2022Article
- Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes.Pharmaceutics · 2022Article
- Reappraising the Value of HIV-1 Vaccine Correlates of Protection Analyses.Journal of virology · 2022Review
- Article
- Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines.Nature communications · 2022Article
- HIV and SARS-CoV-2: Tracing a Path of Vaccine Research and Development.Current HIV/AIDS reports · 2022Review
- Decoding human-macaque interspecies differences in Fc-effector functions: The structural basis for CD16-dependent effector function in Rhesus macaques.Frontiers in immunology · 2022Article
- Induction of food-specific IgG by Gene Gun-delivered DNA vaccines.Frontiers in allergy · 2022Article
- Assessment of an LSDV-Vectored Vaccine for Heterologous Prime-Boost Immunizations against HIV.Vaccines · 2021Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
22 authors.
Funding
Abstract
A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased in two of the trials, suggesting that this vaccine strategy elicited CD4+ T-cell responses that provide more targets for infection, attenuating protection or increasing transmission. The degree to which this problem extends to other HIV vaccine candidates is not known. Here, we show that a gp120-CD4 chimeric subunit protein vaccine (full-length single chain) elicits heterologous protection against simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) acquisition in three independent rhesus macaque repeated low-dose rectal challenge studies with SHIV162P3 or SIVmac251. Protection against acquisition was observed with multiple formulations and challenges. In each study, protection correlated with antibody-dependent cellular cytotoxicity specific for CD4-induced epitopes, provided that the concurrent antivaccine T-cell responses were minimal. Protection was lost in instances when T-cell responses were high or when the requisite antibody titers had declined. Our studies suggest that balance between a protective antibody response and antigen-specific T-cell activation is the critical element to vaccine-mediated protection against HIV. Achieving and sustaining such a balance, while enhancing antibody durability, is the major challenge for HIV vaccine development, regardless of the immunogen or vaccine formulation.
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