+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Protection from lethal coronavirus infection by immunoglobulin fragments

Protection from lethal coronavirus infection by immunoglobulin fragments

Journal of Immunology 154(8): 3975-3984

Molecular mechanisms of in vitro and in vivo virus neutralization by specific Ab remain largely undefined. Murine coronaviruses provide an excellent animal model for such studies. To determine the role of Ab bivalency and the contribution of its Fc portion in the neutralization of viral infectivity and passive protection of mice by an in vitro neutralizing and in vivo protective mAb (7-10A), F(ab')-2 and Fab fragments were generated and their biologic properties were examined. The two fragments reacted in ELISA like the whole Ab against viral Ag or specific anti-idiotypic Abs. The affinity constants of the different Ab preparations were determined by surface plasmon resonance using immobilized anti-idiotypic Abs. The apparent affinity constant of the whole Ab molecule was 7.0 times 10-9 M-1 and was reduced 2-fold for F(ab')-2 fragments and 14-fold for Fab molecules. Like whole Ab, both F(ab')-2 and Fab fragments could neutralize virus in vitro and passively protect mice in vivo. However, the efficiency of in vivo neutralization by Fab fragments was reduced compared with the bivalent molecules, despite almost identical half-lives of both types of Ab fragments. These results demonstrate that in vitro and in vivo virus neutralization mechanisms by this Ab are independent of Fc-mediated functions and bivalency, but are probably influenced by Ab avidity. Also, this is the first report of in vivo protection against a viral infection by Fab fragments of antiviral Ab.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 009263946

Download citation: RISBibTeXText

PMID: 7706736

Related references

Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model. Antiviral Research 137: 125-130, 2017

Protection of mice from lethal coronavirus MHV-A59 infection by monoclonal affinity-purified spike glycoprotein. Advances in Experimental Medicine and Biology 276: 205-210, 1990

Protection from lethal coronavirus infection by affinity-purified spike glycoprotein of murine hepatitis virus, strain A59. Virology 174(1): 87-94, 1990

Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. Journal of Virology 88(19): 11034-11044, 2014

Protection of mice from a lethal coronavirus infection in the central nervous system by adoptive transfer of virus-specific T cell clones. Journal of Neuroimmunology 32(1): 1-9, 1991

Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection. Antiviral Research 132: 141-148, 2016

Protection of mice from lethal Escherichia coli infection by chimeric human bactericidal/permeability-increasing protein and immunoglobulin G1 Fc gene delivery. Antimicrobial Agents and ChemoTherapy 51(2): 724-731, 2007

Memory CD4+ T-cell-mediated protection from lethal coronavirus encephalomyelitis. Journal of Virology 82(24): 12432-12440, 2008

Protection of neonatal calves against K99-E. coli and coronavirus using a colostrum-derived immunoglobulin preparation. Agri Practice 14(5): 13-16, 1993

Protection of neonatal calves against K99-Escherichia coli and coronavirus using a colostrum-derived immunoglobulin preparation. Agri-Practice 14(5): 13-16, 1993

Anticore endotoxin F(ab')2 equine immunoglobulin fragments protect against lethal effects of gram-negative bacterial sepsis. Surgery 96(2): 440-446, 1984

Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. Journal of Virology 81(2): 813-821, 2007

Interference of coronavirus infection by expression of immunoglobulin G (IgG) or IgA virus-neutralizing antibodies. Journal of Virology 71(7): 5251-5258, 1997

Natural course of severe acute respiratory syndrome-associated coronavirus immunoglobulin after infection. Journal of Infectious Diseases 190(9): 1706-7; Author Reply 1707, 2004