safety and immunogenicity of a live-attenuated universal flu vaccine followed by an inactivated universal flu vaccine

Conditions: Influenza; Vaccine

Summary: the clinical study will evaluate safety and the immune response of a prime- boost regimen with a live attenuated influenza vaccine (laiv) prime and an inactivated split influenza vaccine (iiv) boost with or without adjuvant.

this is a prospective, multi-center, randomized, controlled, observer-blind, phase 1 trial in healthy male and female adults 18 through 39 years of age to evaluate safety and the immune response of a prime boost regimen with laiv prime and iiv boost with or without adjuvant. participants will be randomized 4:3:1:3:2 to one of five groups to receive a first dose of study ch8/1n1 laiv (or placebo) or study ch8/1n1 iiv + as03a adjuvant (or placebo) followed three months later by study ch5/1n1 iiv +/- as03a adjuvant (or placebo).

Eligibility criteria:
inclusion criteria: * able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination prior to vaccination. * in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits). * written informed consent obtained from the subject prior to performance of any study specific procedure. * male or non-pregnant female between, and including, 18 and 39 years of age at the time of the first vaccination. * healthy subjects without acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality\*. * female subjects of non-childbearing potential may be enrolled in the study. * female subjects of childbearing potential must have a negative pregnancy test within 24 hours of vaccination. * female subjects of childbearing potential must have practiced adequate contraception for 30 days prior to first vaccination and agree to continue adequate contraception until 2 months after completion of the vaccination series (month 5). * male subjects must be surgically sterile (e.g., vasectomy) or agree to practice adequate contraception from the first vaccination until 2 months after completion of the vaccination series (month 5). please refer to the glossary of terms for the definition of adequate contraception. exclusion criteria: * use of any investigational or non-registered product (drug or vaccine) other than the study vaccines. * any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. * medically diagnosed deviated nasal septum or nasal obstruction. * chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months before the first dose. * administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab) within 6 months before the first dose (visit 03), or planned administration any time during the study period. * planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose (visit 03) up to month 15 (visit 15) * persons who should be annually vaccinated against influenza who live with or care for persons at high risk for influenza-related complications. * history of influenza vaccination within 6 months prior to study enrollment or unwillingness to forego seasonal influenza vaccination during the entire study period. * history of vaccination with an investigational pandemic influenza vaccine other than an 2009 h1n1 pandemic (h1n1pdm09) vaccine. * any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * infection with human immunodeficiency virus regardless of clinical stage of immunodeficiency. * history of current infection with hepatitis b virus or hepatitis c virus regardless of clinical presentation. * history of or current autoimmune disease. * subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of narcolepsy in a subject's parent or sibling. * history of guillain-barré syndrome. * history of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. * hypersensitivity to latex. * administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period. * pregnant or lactating female. * female planning to become pregnant or male planning to father a child or either planning to discontinue contraceptive precautions. * current smoker. * during screening, have a positive test for opiates without a prescription. * history of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. * have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination. * have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations. * have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination. * blood donation or planned blood donation within 30 days prior to the study vaccination through 30 days after the last blood drawn for this study. * have signs or symptoms that could confound or confuse assessment of study vaccine reactogenicity. * any hematological or biochemical parameter that is out of range of normal, and is considered clinically significant by the investigator.

Keywords: live attenuated influenza vaccine inactivated influenza vaccine