title: Putative suppressing effect of IgG Fc-conjugated haemagglutinin (HA) stalk of influenza virus H7N9 on the neutralizing immunogenicity of Fc-conjugated HA head: implication for rational design of HA-based influenza vaccines.
abstract: The emergence of influenza A H7N9 in infection has posed a great threat to public health globally. Poor immunogenicity of H7N9 haemagglutinin (HA) is a major obstacle to the development of an effective H7N9 vaccine. Here, we found that the vaccine containing the H7HA head conjugated with IgG Fc (Hd-Fc) induced strong neutralizing antibody responses and protection against H7N9 infection, whilst the Fc-conjugated H7HA stalk (St-Fc)-based vaccine could not induce neutralizing antibodies, although the St-Fc-immunized mice were partially protected. The vaccines containing the full-length extracellular domain of HA conjugated with Fc and the mixture of Hd-Fc plus St-Fc induced significantly lower neutralizing antibody and haemagglutination inhibition titres than the Hd-Fc-based vaccine. These results suggest that the St-Fc may have inhibitory effects on the neutralizing immunogenicity of Hd-Fc. Therefore, the neutralizing domain(s), such as the receptor-binding domain, in the HA head should be kept and the non-neutralizing domain(s) in the HA stalk with the ability to potentially suppress the neutralizing immunogenicity of HA head should be removed from Fc-conjugated HA-based influenza vaccines to increase the neutralizing antibody response.
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: B
authors.initials: B
authors.lastname: He
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Xia
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and, Shanghai Public Health Clinical Center, Fudan University, Xuhui District, Shanghai 200032, PR China.|Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000378:metabolism*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism*; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004337:Drug Carriers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007141:Immunoglobulin Fc Fragments; D007252:Influenza Vaccines