Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine
Condition: Influenza; Vaccine
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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).
    

Intervention name(s): cH8/1N1 LAIV; AS03-adjuvanted cH5/1N1 IIV; cH5/1N1 IIV; AS03-adjuvanted cH8/1N1 IIV; Normal saline; Phosphate buffered saline (PBS)
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): Live-attenuated influenza virus vaccine (LAIV) expressing chimeric hemagglutinin (HA) with the H8 head and H1 stalk and neuraminidase (NA) subtype 1 (N1) (cH8/1N1):
HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1) containing the backbone of the cold-adapted/temperature sensitive of the Russian LAIV A/Leningrad/134/17/1957 (Len17 IDCDCRG46D).
Administered intranasally as drops at a dose of 10⁷·⁵ (plus or minus ⁰·⁵) 50% egg infectious dose (EID50), formulated in a total volume of 0.5 mL sterile saline (0.25 mL per nostril).; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV) plus AS03 adjuvant: HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1).
Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV):
HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1).
Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Chimeric H8 head with H1 stalk plus N1 (cH8/1N1) inactivated influenza vaccine plus AS03 adjuvant: HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1).
Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Administered intranasally as 0.25 mL nasal drops per nostril; Administered intramuscularly as 0.5 mL injection
Other intervention name(s): cH5/1N1 IIV + AS03 adjuvant; cH8/1N1 IIV + AS03 adjuvant
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible enrolled subjects will be randomized to any of the treatment arms (LAIV-IIV, Groups 1, 2, and 3; or IIV-IIV, Groups 4 and 5) under one allocation sequence, stratified by site, to allow comparability between study groups, such as LAIV-IIV vs IIV-IIV regimens (Groups 1 vs 4). Groups 1-3 will be inpatient and receive either LAIV or placebo as nasal drops at Dose 1. Groups 4-5 ill be outpatient and receive either IIV or placebo as an injection at Dose 1.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: live attenuated influenza vaccine; inactivated influenza vaccine