Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein.
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis® (palivizumab) is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD® phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs) against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction.
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Zhifeng
Z
Chen
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Lan
L
Zhang
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Aimin
A
Tang
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Cheryl
C
Callahan
Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Pavlo
P
Pristatsky
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Ryan
R
Swoyer
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Pedro
P
Cejas
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Debbie
D
Nahas
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Jennifer
J
Galli
Eurofins Lancaster Laboratories Professional Scientific Services, Lancaster, PA, United States of America.
Scott
S
Cosmi
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Daniel
D
DiStefano
Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Van M
VM
Hoang
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Andrew
A
Bett
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Danilo
D
Casimiro
Department of Infectious Diseases and Vaccines Research, Merck Research Laboratories, Merck & Co., Inc., West Point, PA, United States of America.
Kalpit A
http://orcid.org/0000-0001-9844-634X
KA
Vora
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use*; D061505:Cell Surface Display Techniques; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000627:therapeutic use*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity*
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D006023:Glycoproteins; D022261:Respiratory Syncytial Virus Vaccines