Phase I/II trial of a replication-deficient trivalent influenza virus vaccine lacking NS1

• Published in: Vaccine Vol. 31; no. 52; pp. 6194 - 6200
• Main Authors: Mössler, Christina, Groiss, Franz, Wolzt, Michael, Wolschek, Markus, Seipelt, Joachim, Muster, Thomas
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 16.12.2013; Elsevier; Elsevier Limited
• Subjects: Administration, Intranasal; Adolescent; Adult; adults; Allergy and Immunology; antibodies; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Fundamental and applied biological sciences. Psychology; Good Manufacturing Practice; headache; Healthy Volunteers; Humans; Immune response; Immunization; Immunogenicity; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - immunology; Influenza B virus - genetics; Influenza B virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza virus; Intranasal; Live-attenuated; Male; Microbiology; Miscellaneous; NS1; Orthomyxoviridae; Placebos - administration & dosage; Reverse genetics; Rhinitis; seroprevalence; Trivalent; vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Viral infections; Viral Nonstructural Proteins - deficiency; Virology; United States > US; Austria; Trivalent; Intranasal; NS1; Influenza; Reverse genetics; Live-attenuated; Orthomyxoviridae; Vaccine; Intranasal administration; Infection; Virus; Influenzavirus A; Influenza A virus; Viral disease; Phase II trial; Phase I trial; Genetics; Replication; Attenuated strain
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2013.10.061

•We performed the first in man study with a live replication-deficient delNS1-trivalent vaccine.•Significant antibody titers to influenza strains contained in the vaccine were induced.•Seroconversion occurred most frequently in participants who were seronegative before vaccination.•A single intranasal dose was well tolerated and safe in healthy male and female participants.•No vaccine virus could be re-isolated in volunteers after immunization. The non-structural protein NS1 of the influenza virus counteracts the interferon-mediated immune response of the host. We investigated the safety and immunogenicity of a trivalent formulation containing influenza H1N1, H3N2 and B strains lacking NS1 (delNS1-trivalent). Healthy adult study participants who were seronegative for at least one strain present in the vaccine formulation were randomized to receive a single intranasal dose of delNS1-trivalent vaccine at 7.0log10 TCID50/subject (n=39) or placebo (n=41). Intranasal vaccination with the live replication-deficient delNS1-trivalent vaccine was well tolerated with no treatment-related serious adverse events. The most common adverse events identified, i.e. headache, oropharyngeal pain and rhinitis-like symptoms, were mainly mild and transient and distributed similarly in the treatment and placebo groups. Significant vaccine-specific immune responses were induced. Pre-existing low antibody titers or seronegativity for the corresponding vaccine strain yielded better response rates. We show that vaccination with a replication-deficient trivalent influenza vaccine containing H1N1, H3N2 and B strains lacking NS1 is safe and induces significant levels of antibodies (ClinicalTrials.gov identifier NCT01369862).