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.