Monoclonal Antibody against G Glycoprotein Increases Respiratory Syncytial Virus Clearance In Vivo and Prevents Vaccine-Enhanced Diseases

Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract illness in infants, young children, and the elderly. The G glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. We generated two monoclonal...

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Published in:PloS one 2017-01, Vol.12 (1), p.e0169139-e0169139
Main Authors: Lee, Hyo-Jeong, Lee, Jeong-Yoon, Park, Min-Hee, Kim, Joo-Young, Chang, Jun
Format: Article
Language:English
Subjects:
Adenoviruses
Alanine
Amino acids
Animals
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - therapeutic use
Anticoagulants
Antigens
Biology and Life Sciences
Care and treatment
Cell adhesion
Cells, Cultured
Children
Complications and side effects
Disease
Disease Progression
Diseases
Dosage and administration
Epitope mapping
Female
G proteins
Geriatrics
Glycoproteins
Health aspects
Humans
Immune clearance
Immune response
Immune system
Infants
Infections
Injection
Injections
Lungs
Medicine and Health Sciences
Mice
Mice, Inbred BALB C
Monoclonal antibodies
Older people
Pathogenesis
Pediatric diseases
Peptide mapping
Pharmaceutical sciences
Physical Sciences
Proteins
Research and Analysis Methods
Residues
Respiratory syncytial virus
Respiratory Syncytial Virus Infections - pathology
Respiratory Syncytial Virus Infections - prevention & control
Respiratory Syncytial Virus Vaccines - adverse effects
Respiratory Syncytial Virus Vaccines - therapeutic use
Respiratory Syncytial Virus, Human - immunology
Respiratory tract
Respiratory tract infections
Risk factors
Vaccines
Viral Fusion Proteins - immunology
Viral infections
Viruses
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creator Lee, Hyo-Jeong
Lee, Jeong-Yoon
Park, Min-Hee
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Chang, Jun
description Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract illness in infants, young children, and the elderly. The G glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. We generated two monoclonal antibodies (mAbs; 5H6 and 3A5) against G protein core fragment (Gcf), which consisted of amino acid residues 131 to 230 from RSV A2 G protein. Epitope mapping study revealed that 5H6 specifically binds to the G/164-176 peptide that includes conserved sequences shared by both RSV A and B subtypes, and 3A5 binds to the G/190-204 peptide. Studies with mutant Gcf proteins in which cysteine residues were substituted with alanine revealed that 5H6 requires four cysteines for binding and 3A5 binds to Gcf variants with alanine substitutions better than wild-type. To determine if these mAbs reduce pulmonary viral infection, BALB/c mice were administered mAb and subsequently challenged with RSV. On day 4 post-infection, lung viral titers were reduced by up to 93% with the 5H6 injection and 90% with the 3A5 injection, indicating that prophylactic injection of these mAbs contributes to RSV clearance in vivo. Importantly, 5H6 injection reduced vaccine-enhanced diseases. Overall, our results suggest that this novel anti-G mAb could be used as a prophylactic regimen against RSV diseases.
doi_str_mv 10.1371/journal.pone.0169139
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The G glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. We generated two monoclonal antibodies (mAbs; 5H6 and 3A5) against G protein core fragment (Gcf), which consisted of amino acid residues 131 to 230 from RSV A2 G protein. Epitope mapping study revealed that 5H6 specifically binds to the G/164-176 peptide that includes conserved sequences shared by both RSV A and B subtypes, and 3A5 binds to the G/190-204 peptide. Studies with mutant Gcf proteins in which cysteine residues were substituted with alanine revealed that 5H6 requires four cysteines for binding and 3A5 binds to Gcf variants with alanine substitutions better than wild-type. To determine if these mAbs reduce pulmonary viral infection, BALB/c mice were administered mAb and subsequently challenged with RSV. On day 4 post-infection, lung viral titers were reduced by up to 93% with the 5H6 injection and 90% with the 3A5 injection, indicating that prophylactic injection of these mAbs contributes to RSV clearance in vivo. Importantly, 5H6 injection reduced vaccine-enhanced diseases. Overall, our results suggest that this novel anti-G mAb could be used as a prophylactic regimen against RSV diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28076422</pmid><doi>10.1371/journal.pone.0169139</doi><tpages>e0169139</tpages><orcidid>https://orcid.org/0000-0002-8423-5987</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adenoviruses
Alanine
Amino acids
Animals
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - therapeutic use
Anticoagulants
Antigens
Biology and Life Sciences
Care and treatment
Cell adhesion
Cells, Cultured
Children
Complications and side effects
Disease
Disease Progression
Diseases
Dosage and administration
Epitope mapping
Female
G proteins
Geriatrics
Glycoproteins
Health aspects
Humans
Immune clearance
Immune response
Immune system
Infants
Infections
Injection
Injections
Lungs
Medicine and Health Sciences
Mice
Mice, Inbred BALB C
Monoclonal antibodies
Older people
Pathogenesis
Pediatric diseases
Peptide mapping
Pharmaceutical sciences
Physical Sciences
Proteins
Research and Analysis Methods
Residues
Respiratory syncytial virus
Respiratory Syncytial Virus Infections - pathology
Respiratory Syncytial Virus Infections - prevention & control
Respiratory Syncytial Virus Vaccines - adverse effects
Respiratory Syncytial Virus Vaccines - therapeutic use
Respiratory Syncytial Virus, Human - immunology
Respiratory tract
Respiratory tract infections
Risk factors
Vaccines
Viral Fusion Proteins - immunology
Viral infections
Viruses
title Monoclonal Antibody against G Glycoprotein Increases Respiratory Syncytial Virus Clearance In Vivo and Prevents Vaccine-Enhanced Diseases
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