Purpose Of Review: New findings continue to support the notion that broadly crossreactive neutralizing antibody induction is a worthwhile and achievable goal for HIV-1 vaccines. Immunogens are needed that can overcome the genetic variability and complex immune evasion tactics of the virus. Other antibodies might bridge innate and acquired immunity for possible beneficial vaccine effects. This review summarizes progress made over the past year that has enhanced our understanding of humoral immunity as it relates to HIV-1 vaccine development.
Recent Findings: Although a clear path to designing an effective neutralizing antibody-based HIV-1 vaccine remains elusive, there is new information on how antibodies neutralize HIV-1, the epitopes involved, and clues to the possible nature of protective immunogens that keep this goal alive. Moreover, there is a greater understanding of HIV-1 diversity and its possible limits under immune pressure. Other antibodies might possess antiviral activity by mechanisms involving Fc receptor engagement or complement activation that would be of value for HIV-1 vaccines.
Summary: Recent developments strengthen the rationale for antibody-based HIV-1 vaccine immunogens and provide a stronger foundation for vaccine discovery.
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http://dx.doi.org/10.1097/COH.0b013e3280ef691e | DOI Listing |
Noncoding RNA
January 2025
Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations.
View Article and Find Full Text PDFFront Immunol
January 2025
Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies.
View Article and Find Full Text PDFA primary goal in the development of an AIDS vaccine is the elicitation of broadly neutralizing antibodies (bNAbs) that protect against diverse HIV-1 strains. To this aim, germline-targeting immunogens have been developed to activate bNAb precursors and initiate the induction of bNAbs. While most pre-clinical germline-targeting HIV-1 vaccine candidates only target a single bNAb precursor epitope, an effective HIV-1 vaccine will likely require bNAbs that target multiple epitopes on Env.
View Article and Find Full Text PDFCell Rep
January 2025
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address:
Broadly neutralizing antibodies (bNAbs) targeting the apex of the HIV-1-envelope (Env) trimer comprise the most potent category of HIV-1 bNAbs and have emerged as promising therapeutics. Here, we investigate the development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage and report cryo-EM structures at 3.4 Å resolution of PGDM1400 and of an improved PGT145 variant (PGT145-R100aS), each bound to the BG505 Env trimer.
View Article and Find Full Text PDFSci Immunol
January 2025
Department of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated.
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