Highly active engineered IgG3 antibodies against SARS-CoV-2.
Proc Natl Acad Sci U S A
; 118(42)2021 10 01.
Article
in English
| MEDLINE | ID: covidwho-1447423
ABSTRACT
Monoclonal antibodies (mAbs) that efficiently neutralize SARS-CoV-2 have been developed at an unprecedented speed. Notwithstanding, there is a vague understanding of the various Ab functions induced beyond antigen binding by the heavy-chain constant domain. To explore the diverse roles of Abs in SARS-CoV-2 immunity, we expressed a SARS-CoV-2 spike protein (SP) binding mAb (H4) in the four IgG subclasses present in human serum (IgG1-4) using glyco-engineered Nicotiana benthamiana plants. All four subclasses, carrying the identical antigen-binding site, were fully assembled in planta and exhibited a largely homogeneous xylose- and fucose-free glycosylation profile. The Ab variants ligated to the SP with an up to fivefold increased binding activity of IgG3. Furthermore, all H4 subtypes were able to neutralize SARS-CoV-2. However, H4-IgG3 exhibited an up to 50-fold superior neutralization potency compared with the other subclasses. Our data point to a strong protective effect of IgG3 Abs in SARS-CoV-2 infection and suggest that superior neutralization might be a consequence of cross-linking the SP on the viral surface. This should be considered in therapy and vaccine development. In addition, we underscore the versatile use of plants for the rapid expression of complex proteins in emergency cases.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Immunoglobulin G
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Antibodies, Monoclonal
/
Antibodies, Viral
Type of study:
Observational study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Pnas.2107249118
Similar
MEDLINE
...
LILACS
LIS