Intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal IgA antibodies in humans

• Published in: Vaccine Vol. 32; no. 17; pp. 1897 - 1900
• Main Authors: Morokutti, A, Muster, T, Ferko, B
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 07.04.2014; Elsevier; Elsevier Limited
• Subjects: Administration, Intranasal; Allergy and Immunology; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Applied microbiology; Avian flu; Biological and medical sciences; Cell culture; Cross Protection; Cross-reactive antibodies; delNS1 influenza virus vaccine; Double-Blind Method; Enzymes; Fundamental and applied biological sciences. Psychology; Hemagglutination Inhibition Tests; Heterologous immunity; Humans; Immune system; Immunity, Mucosal; Immunization; Immunoglobulin A - immunology; Immunoglobulin G - blood; Infections; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza Vaccines - therapeutic use; Influenza virus; Influenza, Human - prevention & control; Microbiology; Miscellaneous; Nasal wash IgA; Neutralization Tests; Pandemics; Single intranasal immunisation; Swine flu; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Inactivated - immunology; Viral infections; Virology; Viruses; Volunteers; Cross-reactive antibodies; Nasal wash IgA; Single intranasal immunisation; delNS1 influenza virus vaccine; Heterologous immunity; Human; IgA; Immunization; deINS1 influenza virus vaccine; Vaccination; Orthomyxoviridae; Vaccine; Intranasal administration; Influenzavirus; Neutralizing antibody; Virus; Local immunity; Influenzavirus A; Influenza A virus; Replication
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2014.02.009

Abstract 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 (7.7 log10 TCID50 /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.