title: Intranasally administered Endocine formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets.
abstract: Influenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. There is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. Endocine is a lipid-based mucosal adjuvant composed of endogenous lipids found ubiquitously in the human body. Intranasal administration of influenza antigens mixed with this adjuvant has been shown to induce local and systemic immunity as well as protective efficacy against homologous influenza virus challenge in mice. Here we used ferrets, an established animal model for human influenza virus infections, to further investigate the potential of Endocine as an adjuvant. Intranasal administration of inactivated pandemic H1N1/California/2009 split antigen or whole virus antigen mixed with Endocine induced high levels of serum hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers that were also cross reactive against distant swine viruses of the same subtype. HI and VN antibody titers were already demonstrated after a single nasal immunization. Upon intratracheal challenge with a homologous challenge virus (influenza virus H1N1/The Netherlands/602/2009) immunized ferrets were fully protected from virus replication in the lungs and largely protected against body weight loss, virus replication in the upper respiratory tract and pathological changes in the respiratory tract. Endocine formulated vaccines containing split antigen induced higher HI and VN antibody responses and better protection from body weight loss and virus shedding in the upper respiratory tract than the Endocine formulated vaccine containing whole virus antigen.
authors.affiliation: Eurocine Vaccines AB, Karolinska Institutet Science Park, 171 65 Solna, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Maltais
authors.affiliation: Viroclinics Biosciences B.V., 3029 AK Rotterdam, The Netherlands.
authors.forename: Koert J
authors.initials: KJ
authors.lastname: Stittelaar
authors.affiliation: Viroclinics Biosciences B.V., 3029 AK Rotterdam, The Netherlands.
authors.forename: Edwin J B
authors.initials: EJ
authors.lastname: Veldhuis Kroeze
authors.affiliation: Viroclinics Biosciences B.V., 3029 AK Rotterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Department of Radiology, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: Marcel L
authors.initials: ML
authors.lastname: Dijkshoorn
authors.affiliation: Department of Radiology, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Krestin
authors.affiliation: Eurocine Vaccines AB, Karolinska Institutet Science Park, 171 65 Solna, Sweden.
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.affiliation: Eurocine Vaccines AB, Karolinska Institutet Science Park, 171 65 Solna, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Arwidsson
authors.affiliation: Eurocine Vaccines AB, Karolinska Institutet Science Park, 171 65 Solna, Sweden.
authors.forename: Alf
authors.initials: A
authors.lastname: Lindberg
authors.affiliation: Viroclinics Biosciences B.V., 3029 AK Rotterdam, The Netherlands; Department of Viroscience, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands. Electronic address: a.osterhaus@erasmusmc.nl.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D056738:Cross Protection; D003429:Cross Reactions; D005260:Female; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D012137:Respiratory System / Q000821:virology; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: Adjuvants; Computed tomography; Ferret; Influenza vaccine; Intranasal