Safety and Immunogenicity of a Live Attenuated H7N9 Influenza Virus Vaccine in Healthy Adults
Safety and Immunogenicity of a Live Attenuated H7N9 Influenza Virus Vaccine in Healthy Adults
H7N9 avian influenza (AI) viruses have caused a recent outbreak of severe respiratory disease
 in humans in China. The purpose of this study is to evaluate the safety and immunogenicity of
 a live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine in healthy adults. A single dose
 of inactivated subvirion H7N9 influenza vaccine will be administered 3 months later.
H7N9 AI viruses have recently caused a large outbreak of severe respiratory disease in humans
 in China. A vaccine for use in the event of an H7N9 AI pandemic is an important research
 priority. Previous studies have shown that when subjects who received a live bird flu vaccine
 received a subsequent "booster" dose of inactivated bird flu vaccine, a vigorous antibody
 response was detected. The inactivated vaccine served as a way to probe the immune response
 to the initial live vaccine. The purpose of this study is to evaluate the safety,
 infectivity, and immunogenicity of a live attenuated H7N9 A/Anhui/13 ca influenza virus
 vaccine in healthy adults, and to administer a booster dose of an inactivated subvirion H7N9
 influenza vaccine 3 months later.

 This study will enroll healthy adults who are willing to remain in an isolation unit in an
 inpatient clinic for several days during the study. They will be randomly assigned to receive
 either one dose (Group 1) or two doses (Group 2) of the live attenuated H7N9 A/Anhui/13 ca
 influenza virus vaccine, which will be delivered by a nasal spray device. Participants in
 both groups will receive one "booster" dose of inactivated subvirion H7N9 influenza vaccine 3
 months later in an outpatient setting. All participants will be admitted to the inpatient
 clinic and will receive one dose of the live attenuated H7N9 A/Anhui/13 ca influenza virus
 vaccine 2 days after entering the clinic. Participants will remain in the inpatient clinic
 for approximately 9 days after receiving the vaccine. While in the clinic, participants will
 undergo medical history reviews, blood collections, urine collections, physical examinations,
 nasal wash procedures, and vital sign measurements.

 Participants in Group 1 will attend a study visit at Day 28 and undergo a medical history
 review, blood collection, and a nasal wash. Participants in Group 2 will be readmitted to the
 inpatient clinic 2 days prior to receiving a second dose of the live attenuated H7N9
 A/Anhui/13 ca influenza virus vaccine at Day 28. They will remain in the clinic for
 approximately 9 days after receiving the vaccine; while in the clinic, they will take part in
 the same study procedures as during the first inpatient visit.

 All participants will attend a study visit at Day 56 and undergo a medical history review,
 blood collection, and a nasal wash. At Day 98, all participants will receive one "booster"
 dose of the inactivated subvirion H7N9 influenza vaccine, as outpatients. They will attend
 additional study visits on Days 101, 105, 112, 126, 154, and 180, which may include medical
 history reviews; physical examinations; and urine, blood, and nasal secretion collections.
Inclusion Criteria:

 -  Adult males and non-pregnant females between 18 years and 49 years of age, inclusive.
 Children will not be recruited or enrolled in this study because they are not in the
 apparent risk group, and for safety considerations and because of the need for
 isolation.

 -  General good health, without significant medical illness, physical examination
 findings, or significant laboratory abnormalities as determined by the investigator

 -  Agree to storage of blood specimens for future research

 -  Available for the duration of the trial

 -  Willingness to participate in the study as evidenced by signing the informed consent
 document

 -  Female participants of child-bearing potential must agree to use effective birth
 control methods for the duration of the study (for example, pharmacologic
 contraceptives including oral, parenteral, and transcutaneous delivery; condoms with
 spermicide; diaphragm with spermicide; intrauterine device; abstinence from
 heterosexual intercourse; surgical sterilization). All female participants will be
 considered being of child-bearing potential except those who have undergone
 hysterectomy and those in whom menopause occurred at least 1 year prior to the study.

 Exclusion Criteria:

 -  Pregnancy, as determined by a positive human choriogonadotropin (beta-HCG) test

 -  Currently breastfeeding

 -  Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
 rheumatologic, autoimmune, or renal disease by history, physical examination, and/or
 laboratory studies including urine testing. Alanine aminotransferase (ALT) levels
 greater than two times the upper normal limit will be exclusionary at baseline, prior
 to vaccination.

 -  Behavioral or cognitive impairment or psychiatric disease that in the opinion of the
 investigator affects the ability of the participant to understand and cooperate with
 the study protocol

 -  Previous enrollment in an H7 influenza vaccine trial or in any study of an avian
 influenza vaccine

 -  Seropositive to the H7N9 influenza A virus (serum HAI titer greater than 1:8)

 -  Positive urine drug toxicology test indicating narcotic use/dependency

 -  Have medical, occupational, or family problems as a result of alcohol or illicit drug
 use during the past 12 months

 -  Other condition that in the opinion of the investigator would jeopardize the safety or
 rights of a participant in the trial or would render the participant unable to comply
 with the protocol

 -  History of anaphylaxis

 -  Allergy to oseltamivir as determined by participant report

 -  Current diagnosis of asthma or reactive airway disease (within the past 2 years)

 -  History of Guillain-Barré Syndrome

 -  Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1
 (HIV-1)

 -  Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay) for
 hepatitis C virus (HCV)

 -  Positive hepatitis B virus surface antigen (HBsAg) by ELISA

 -  Known immunodeficiency syndrome

 -  Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs
 within 30 days prior to vaccination

 -  Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to
 study vaccination

 -  History of asplenia

 -  Receipt of blood or blood-derived products (including immunoglobulin) within 6 months
 prior to study vaccination

 -  Current smoker unwilling to stop smoking for the duration of the study:

 -  A current smoker includes anyone stating they currently smoke any amount of a
 tobacco product.

 -  The decision to exclude a potential participant is determined by medical history
 and a clinician's clinical judgment based on the physical examination.

 -  After admission to the unit, nicotine patches will be provided to current smokers
 who request them for the inpatient portion of the study.

 -  Travel to the Southern Hemisphere within 14 days prior to study vaccination

 -  Travel on a cruise ship within 14 days prior to study vaccination

 -  Receipt of another investigational vaccine or drug within 30 days prior to study
 vaccination

 -  Allergy to eggs or egg products