Fab-dimerized glycan-reactive antibodies neutralize HIV and are prevalent in humans and rhesus macaques
Williams, W. B.; Meyerhoff, R.; Edwards, R. J.; Li, H.; Nicely, N.; Henderson, R.; Zhou, Y.; Janowska, K.; Mansouri, K.; Manne, K.; Stalls, V.; Hsu, A. L.; Borgnia, M. J.; Stewart-Jones, G.; Lee, M. S.; Bronkema, N.; Perfect, J.; Moody, A.; Wiehe, K.; Bradley, T.; Kepler, T. B.; Alam, M.; Parks, R. J.; Foulger, A.; Bonsignori, M.; LaBranche, C. C.; Montefiori, D. C.; Seaman, M.; Santra, S.; Francica, J. R.; Lynn, G. M.; Aussedat, B.; Walkowicz, W. E.; Laga, R.; Kelsoe, G.; Saunders, K. O.; Fera, D.; Kwong, P. D.; Seder, R. A.; Bartesaghi, A.; Shaw, G. M.; Acharya, P.; Haynes, B. F.
Show abstract
SummaryThe HIV-1 envelope (Env) is comprised by mass of over 50% glycans. A goal of HIV-1 vaccine development is the induction of Env glycan-reactive broadly neutralizing antibodies (bnAbs). The 2G12 bnAb recognizes an Env glycan cluster using a unique variable heavy (VH) domain-swapped conformation that results in fragment antigen-binding (Fab) dimerization. Here we describe Fab-dimerized glycan (FDG)-reactive antibodies without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques that neutralized heterologous HIV-1 isolates. FDG precursors were boosted by vaccination in macaques, and were present in HIV-1-naïve humans with an average estimated frequency of one per 340,000 B cells. These data demonstrate frequent HIV-1 Env glycan-reactive bnAb B cell precursors in macaques and humans and reveal a novel strategy for their induction by vaccination.HighlightsDiscovery of Fab-dimerized HIV-1 glycan-reactive antibodies with a non-domain-swapped architectureFab-dimerized antibodies neutralize heterologous HIV-1 isolates.Antibodies with this architecture can be elicited by vaccination in macaques.Fab-dimerized antibodies are found in HIV-1 naïve humans.Competing Interest StatementThe authors have declared no competing interest.View Full Text
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth 97%
- Broadly neutralizing antibodies target the coronavirus fusion peptide 97%
- Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants 97%
Similar papers in this journal
- Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease 98%
- Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants 96%
- HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections 96%
Similar papers in this journal
- Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques 98%
- Vaccine Elicitation of HIV-1 Neutralizing Antibodies Against Both V2 Apex and Fusion Peptide in Rhesus Macaques 98%
- Paired heavy and light chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses 97%
Similar papers in this journal
- Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation 95%
- A SARS-CoV-2 vaccine candidate would likely match all currently circulating strains 95%
- Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.