Vaccination with drifted variants of avian H5 hemagglutinin protein elicits a broadened antibody response that is protective against challenge with homologous or drifted live H5 influenza virus

• Published in: Vaccine Vol. 29; no. 48; pp. 8888 - 8897
• Main Authors: Santiago, Felix W., Fitzgerald, Theresa, Treanor, John J., Topham, David J.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 08.11.2011; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; animal models; Animals; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody; Antibody Formation; Antigens; Applied microbiology; Avian flu; B cells; Biological and medical sciences; birds; blood serum; Cross Protection; cross reaction; Cross Reactions; Deoxyribonucleic acid; Disease Models, Animal; DNA; enzyme-linked immunosorbent assay; Fundamental and applied biological sciences. Psychology; Genetic Drift; Hemagglutinin; Hemagglutinin Glycoproteins, Influenza Virus - immunology; hemagglutinins; Human subjects; humans; immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunology; Infections; influenza; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza virus; Male; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Mortality; neutralization; Neutralization Tests; neutralizing antibodies; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; pandemic; Proteins; Studies; vaccination; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral infections; Virology; Viruses; Vaccine; Immunology; B cells; Influenza virus; Hemagglutinin; Antibody; Immune response; Vaccination; Orthomyxoviridae; B-Lymphocyte; Influenzavirus; Protein; Virus; Vertebrata; Aves; Humoral immunity
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2011.09.069

► H5VN04 and H5IN05 rHA are used in drifted variant vaccination strategy. ► Vaccine tunes reactivity to drifted variant without loss of reactivity to priming HA. ► Low incidence of neutralizing Ig generated to a virus containing the drifted HA. ► HA-specific cross-reactive, but not neutralizing, Ig are sufficient for protection. Substantial H5 influenza HA directed immunity is elicited after vaccination of human subjects who had been previously immunized with a drifted H5 HA variant. We sought to investigate the characteristics of H5 HA specific immune responses in more depth by developing an animal model of H5 HA vaccination using drift variants of recombinant H5 HA proteins. HA proteins derived from influenzas A/Vietnam/1203/04 (Clade 1) and A/Indonesia/05/05 (Clade 2.1) were chosen. The sequence of vaccination consisted of two doses of homologous protein, followed by one additional dose of the homologous or heterologous, drifted HA protein. Each dose of HA was combined with CpG as an adjuvant and was injected subcutaneously. All the animals exhibited a serum IgG antibody response that cross-reacted with both HAs in an ELISA. However, those animals that received the drifted variant exhibited higher reactivity to the heterologous HA. Competitive ELISA of serum from drift-variant recipients showed evidence of antibody focusing towards the drifted HA, suggesting modification of the response towards improved cross-reactivity, though development of neutralizing antibodies was limited. Nevertheless, animals were protected against live-virus challenge, and passive transfer of serum was sufficient to confer protection to otherwise naïve mice, indicating that both neutralizing and non-neutralizing antibodies offer some degree of protection. These findings suggest that pre-vaccination against H5 influenza has the potential to prime immunity against emerging drifted H5 strains, and could also lower the dose requirements of vaccination in the event of a pandemic.