Fab-dimerized glycan-reactive antibodies neutralize HIV and are prevalent in humans and rhesus macaques
Summary
The 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.
Highlights
Discovery of Fab-dimerized HIV-1 glycan-reactive antibodies with a non-domain-swapped architecture
Fab-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 Statement
The authors have declared no competing interest.
Subject Area
- Biochemistry (11718)
- Bioengineering (8724)
- Bioinformatics (29132)
- Biophysics (14936)
- Cancer Biology (12051)
- Cell Biology (17360)
- Clinical Trials (138)
- Developmental Biology (9406)
- Ecology (14146)
- Epidemiology (2067)
- Evolutionary Biology (18269)
- Genetics (12223)
- Genomics (16768)
- Immunology (11844)
- Microbiology (28016)
- Molecular Biology (11560)
- Neuroscience (60822)
- Paleontology (450)
- Pathology (1864)
- Pharmacology and Toxicology (3231)
- Physiology (4940)
- Plant Biology (10401)
- Synthetic Biology (2878)
- Systems Biology (7333)
- Zoology (1642)