TY - JOUR
T1 - An H7N1 influenza virus vaccine induces broadly reactive antibody responses against H7N9 in humans
AU - Krammer, Florian
AU - Jul-Larsen, Åsne
AU - Margine, Irina
AU - Hirsh, Ariana
AU - Sjursen, Haakon
AU - Zambon, Maria
AU - Cox, Rebecca J.
PY - 2014/8
Y1 - 2014/8
N2 - Emerging H7N9 influenza virus infections in Asia have once more spurred the development of effective prepandemic H7 vaccines. However, many vaccines based on avian influenza viruses - including H7 - are poorly immunogenic, as measured by traditional correlates of protection. Here we reevaluated sera from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses to divergent H7 strains, including H7N9, dissected the antibody response into head- and stalk-reactive antibodies, and tested the in vivo potency of these human sera in a passive-transfer H7N9 challenge experiment with mice. Although only a low percentage of vaccinees induced neutralizing antibody responses against the homologous vaccine strain and also H7N9, we detected strong cross-reactivity to divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination induced antibodies to both the head and stalk domains of the HA, which is in sharp contrast to seasonal inactivated vaccines. Finally, we were able to show that both neutralizing and nonneutralizing antibodies improved in vivo virus clearance in a passive-transfer H7N9 challenge mouse model.
AB - Emerging H7N9 influenza virus infections in Asia have once more spurred the development of effective prepandemic H7 vaccines. However, many vaccines based on avian influenza viruses - including H7 - are poorly immunogenic, as measured by traditional correlates of protection. Here we reevaluated sera from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses to divergent H7 strains, including H7N9, dissected the antibody response into head- and stalk-reactive antibodies, and tested the in vivo potency of these human sera in a passive-transfer H7N9 challenge experiment with mice. Although only a low percentage of vaccinees induced neutralizing antibody responses against the homologous vaccine strain and also H7N9, we detected strong cross-reactivity to divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination induced antibodies to both the head and stalk domains of the HA, which is in sharp contrast to seasonal inactivated vaccines. Finally, we were able to show that both neutralizing and nonneutralizing antibodies improved in vivo virus clearance in a passive-transfer H7N9 challenge mouse model.
UR - http://www.scopus.com/inward/record.url?scp=84906670725&partnerID=8YFLogxK
U2 - 10.1128/CVI.00272-14
DO - 10.1128/CVI.00272-14
M3 - Article
C2 - 24943383
AN - SCOPUS:84906670725
SN - 1556-6811
VL - 21
SP - 1153
EP - 1163
JO - Clinical and Vaccine Immunology
JF - Clinical and Vaccine Immunology
IS - 8
ER -