Measuring antibody responses to a live attenuated influenza vaccine in children.
BACKGROUND
Hemagglutination inhibition (HAI) assay is the standard method for evaluating inactivated influenza vaccines, but no standard assay has been established for evaluating live attenuated influenza vaccines (LAIV). LAIV containing A/Beijing/262/95(H1N1) induced low serum HAI antibody responses to the antigenic variant, A/New Caledonia/20/99(H1N1) in a serologic study but provided protection against the A/New Caledonia-like viruses in a community study. Neutralization and HAI assays were compared by measuring H1N1 cross-reactive antibody responses to the LAIV in children.


METHODS
Sera were collected from 50 children 1-8 years of age before vaccination and 4-6 weeks after each dose of the LAIV. Antibody titers to the 3 vaccine viruses were measured by the HAI assay, whereas antibody titers against the H1N1 vaccine virus (A/Beijing/262/95) and 2 H1N1 antigenic variants (A/Shenzhen/227/95 and A/New Caledonia/20/99) were measured by the HAI and neutralization assays.


RESULTS
Initially seronegative participants were more likely to develop HAI seroconversion responses to the 3 vaccine viruses than the baseline seropositive participants (77% versus 14% for H1N1, 100% versus 20% for H3N2, 100% versus 19% for B, P < 0.01, Fisher's exact test). For the H1N1 cross-reactive antibody responses, seroconversion rates measured by the neutralization assay were significantly higher than those measured by the HAI assay (95% versus 78%, P = 0.0485 for A/Beijing/262/95; 75% versus 24%, P < 0.0001 for A/Shenzhen/227/95; 51% versus 5%, P < 0.0001 for A/New Caledonia/20/99).


CONCLUSIONS
The neutralization assay was more sensitive than the HAI assay for measuring H1N1 antibody responses after vaccination of children with the LAIV and may provide a better correlate of clinical protection provided by the LAIV.
Lee
Min-Shi
MS
MedImmune Vaccines, Mountain View, CA, USA.
Mahmood
Kutubuddin
K
Adhikary
Lopa
L
August
Marilyn J
MJ
Cordova
Julie
J
Cho
Iksung
I
Kemble
George
G
Reisinger
Keith
K
Walker
Robert E
RE
Mendelman
Paul M
PM
D000914:Antibodies, Viral / Q000032:analysis*; D000917:Antibody Formation / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007115:Immunization Schedule; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D011336:Probability; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated