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

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0169139

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.