Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G
Kristina Borochova,
Katarzyna Niespodziana,
Katarina Stenberg Hammar,
Marianne van Hage,
Gunilla Hedlin,
Cilla Söderhäll,
Margarete Focke-Tejkl,
Rudolf Valenta
Affiliations
Kristina Borochova
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
Katarzyna Niespodziana
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
Katarina Stenberg Hammar
Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
Marianne van Hage
Division of Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital, 171 77 Stockholm, Sweden
Gunilla Hedlin
Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
Cilla Söderhäll
Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
Margarete Focke-Tejkl
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
Rudolf Valenta
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies can protect against infection. We expressed the surface-exposed part of A2 strain-derived G (A2-G) in baculovirus-infected insect cells and synthesized overlapping peptides spanning complete A2-G. The investigation of the natural IgG response of adult subjects during a period of one year showed that IgG antibodies (i) recognize G significantly stronger than the fusion protein F0, (ii) target mainly non-conformational, sequential peptide epitopes from the exposed conserved region but also buried peptides, and (iii) exhibit a scattered but constant recognition profile during the observation period. The IgG subclass reactivity profile (IgG1 > IgG2 > IgG4 = IgG3) was indicative of a mixed Th1/Th2 response. Two strongly RSV-neutralizing sera including the 1st WHO standard contained high IgG anti-G levels. G-specific IgG increased strongly in children after wheezing attacks suggesting RSV as trigger factor. Our study shows that RSV G and G-derived peptides are useful for serological diagnosis of RSV-triggered exacerbations of respiratory diseases and underlines the importance of G for development of RSV-neutralizing vaccines.
