Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease

• Published in: PLoS pathogens Vol. 16; no. 5; p. e1008517
• Main Authors: Powell, Laura A., Fox, Julie M., Kose, Nurgun, Kim, Arthur S., Majedi, Mahsa, Bombardi, Robin, Carnahan, Robert H., Slaughter, James C., Morrison, Thomas E., Diamond, Michael S., Crowe, James. E.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2020; Public Library of Science (PLoS)
• Subjects: Alphavirus Infections - immunology; Alphavirus Infections - pathology; Alphavirus Infections - prevention & control; Animals; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; Antibodies, Viral - immunology; Antibodies, Viral - pharmacology; Antibody response; Antigens; Biology and Life Sciences; Capsid Proteins - immunology; Cell culture; Chikungunya virus; Chlorocebus aethiops; Disease transmission; E2 protein; Epidemics; Epitope mapping; Epitopes - immunology; Female; Fever; Glycoproteins; Health aspects; Host-virus relationships; Humans; Humoral immunity; Immunology; Infections; Infectivity; Medicine; Medicine and Health Sciences; Mice; Middle Aged; Monoclonal antibodies; Mosquitoes; Neutralizing; Observations; Pathology; Pediatrics; Polyarthritis; Proteins; Research and Analysis Methods; Rivers; RNA viruses; Ross River virus - immunology; Software; Supervision; Vaccines; Vero Cells; Viral diseases; Viral Envelope Proteins - immunology; Virus attachment; Viruses; Australia; United States > US; Tennessee; Nashville Tennessee; Missouri
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008517

Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, and fusion. Some of the most potently neutralizing mAbs inhibited binding of RRV to Mxra8, a recently discovered alpahvirus receptor. Epitope mapping studies identified the A and B domains of the RRV E2 protein as the major antigenic sites for the human neutralizing antibody response. In experiments in mice, these mAbs were protective against cinical disease and reduced viral burden in multiple tissues, suggesting a potential therapeutic use for humans.