Intranasal vaccination with a replication-deficient influenza virus induces
heterosubtypic neutralising mucosal IgA antibodies in humans.
Author(s): Morokutti A(1), Muster T(2), Ferko B(3).
Affiliation(s): Author information:
(1)AVIR Green Hills Biotechnology AG, Vienna, Austria; University of Natural
Resources and Life Sciences, Vienna, Austria.
(2)AVIR Green Hills Biotechnology AG, Vienna, Austria.
(3)AVIR Green Hills Biotechnology AG, Vienna, Austria. Electronic address:
efbio6@gmail.com.
Publication date & source: 2014, Vaccine. , 32(17):1897-900
We investigated the cross-neutralising potential of serum and nasal wash samples
from volunteers who were intranasally immunised once with a monovalent
replication-deficient delNS1-H1N1 influenza virus vaccine
(7.7log10TCID50/volunteer). Eight out of twelve (8/12) vaccinees responded to
vaccination with a significant increase of antibody levels in serum IgG ELISA,
mucosal IgA ELISA, MNA or HAI. Four responders showed delNS1-specific ELISA IgA
increases and revealed excellent homosubtypic neutralising activity in serum and
mucosal washings (4/4). However, 0/4 of the sera but 3/4 of the nasal washings
neutralised also heterosubtypic H3N2 and H5N1 influenza viruses. Depletion
experiments proved that IgA but not IgG is responsible for the cross-neutralising
activity of the nasal wash sample. Our findings indicate that the induction of
virus-neutralising IgA may represent a valuable correlate of cross-protection of
intranasal influenza vaccines and that the delNS1 concept constitutes a promising
approach to protect humans from seasonal and pandemic influenza threats.CLINICAL
TRIAL REGISTRATION: NCT00724997.
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