AI Article Synopsis
- Immunodominance of antibodies targeting non-neutralizing epitopes and high somatic hypermutation in germinal centers (GCs) are major challenges in developing a successful HIV vaccine.
- The study utilized implantable osmotic pumps to deliver epitope-targeted immunogens to rhesus macaques, aiming to enhance antibody responses against the conserved fusion peptide over six months.
- Results indicated that while antibody responses against the FP/N611 glycan hole were primed, they showed limited neutralization breadth, and cryoEMPEM revealed key residue information to guide future vaccine design.
Article Abstract
Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245479 | PMC |
| http://dx.doi.org/10.1038/s41541-024-00918-9 | DOI Listing |
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