Focusing antibody responses to the fusion peptide in rhesus macaques.
Christopher A CottrellPayal P PratapKimberly M CirelliDiane G CarnathanChiamaka A EnemuoAleksandar AntanasijevicGabriel OzorowskiLeigh M SewallHongmei GaoKelli M GreeneJoel D AllenJulia T NgoYury ChoeBartek NogalMurillo SilvaJinal N BhimanMatthias G PauthnerDarrell J IrvineDavid C MontefioriMax CrispinDennis R BurtonGuido SilvestriShane CrottyAndrew B WardPublished in: bioRxiv : the preprint server for biology (2023)
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 elicit immune responses against the conserved fusion peptide. Antibody specificities and GC responses were tracked longitudinally using electron microscopy polyclonal epitope mapping (EMPEM) and lymph node fine-needle aspirates, respectively. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
Keyphrases
- lymph node
- antiretroviral therapy
- hiv positive
- hiv testing
- hiv infected
- immune response
- human immunodeficiency virus
- electron microscopy
- hepatitis c virus
- hiv aids
- cancer therapy
- men who have sex with men
- air pollution
- south africa
- transcription factor
- dendritic cells
- copy number
- monoclonal antibody
- neoadjuvant chemotherapy
- dna methylation
- mass spectrometry
- toll like receptor
- radiation therapy
- drug delivery
- gene expression
- protein protein
- rectal cancer
- sentinel lymph node
- human health