Follow-up study to determine the safety, maximum tolerable dose and ability to provoke an immune response of the Codavax intranasal Influenza Vaccine in healthy adult volunteers..

INTERVENTION: A randomized, single‐blind, placebo‐ and active‐controlled, Phase I study with 64 sero‐susceptible individuals aged 18 to 45 years. A total of 64 healthy individuals will be enrolled and randomized into 3 groups where each participant will receive a single dose of either CodaVax‐H1N1, or FluMist® Comparator – 2018/19 or placebo (27:27:10). Participants will receive one 0.1ml into both nostrils (one immediately after the other). Twenty‐seven (27) participants will be administered CodaVax‐H1N1, 10 participants will be administered a placebo and 27 participants will be administered the quadrivalent influenza vaccine, FluMist "Registered Trademark". All subjects will receive an intranasal (IN) dose of either CodaVax‐H1N1, FluMist or saline (placebo). Arm 1: Intranasal dose of CodaVax‐H1N1 Arm 2: Intranasal dose of FluMist Quadrivalent Comparator ‐ 2018/19 Arm 3: Intranasal dose of Placebo (Saline) CodaVax‐H1N1 is a potential universal live attenuated influenza vaccine (LAIV) manufactured using a proprietary SAVE platform based on the H1N1 A/California/07/2009 (H1N1) strain. The vaccination dose will be 8 x 10^5 PFU in 200 microlitre of current Good Manufacturing Practice (cGMP) Dulbecco Modified Eagle Medium media and 7.5% sucrose, and is to be administered through an intranasal sprayer into one or both nostrils. FluMist is an LAIV which contains haemagglutinin of four different influenza strains. These are A/Slovenia/2903/2015 (H1N1) (anA/Michigan/45/2015 (H1N1)pdm09 ‐like virus), A/New Caledonia/71/2014 (H3N2) (an A/Hong Kong/4801/2014 (H3N2)‐ like virus, B/Phuket/3073/2013 (B/Yamagata/16/88 lineage) and B/Brisbane/60/2008 (B/Victoria/2/87 Lineage). Dose will be 0.2ml FluMist intranasal spray (0.1mL per nostril). As the CodaVax‐H1N1 dose is 8‐times higher than the highest dose administered in the first clinical trial (UTN: U1111‐1191‐3515), the first 5 participants dosed with CodaVax‐H1N1 will be sentinel participants. CONDITION: Infection ‐ Studies of infection and infectious agents Influenza; ; Influenza ; This will be assessed by blood serum assay at day 6 and day 30 as compared to the blood serum assay at baseline (day 0 pre‐dose).[At Day 0 and Day 28‐35 after vaccination. ] INCLUSION CRITERIA: 1. Adult volunteers, aged 18 to 45 years (at the time of screening). a. In good general health in the opinion of the Medical Investigator or delegate, with no significant medical history and no clinically significant abnormal findings at screening. Participants with minor medical problems (for example, mild gastro‐oesophageal reflux), which are unlikely to interfere with participant safety, the study procedures and/or results, and are not excluded elsewhere in the protocol, may be included at the discretion of the Medical Investigator. Furthermore, medications which are unlikely to interfere with participant safety, study procedures and/or results, and which are not excluded elsewhere in the protocol, may be permitted at the discretion of the Medical Investigator. 2. Participants must use highly effective, double contraception from the Screening Visit and up to the Follow‐up Visit (Day 30). Double contraception is defined as a condom AND one other form of t PRIMARY OUTCOME: The primary outcome of this study is the assessment of the safety profile and tolerability of CodaVax‐H1N1 influenza vaccine compared to active and placebo controls when administered to healthy adults. This is a composite primary outcome and will be tested by clinical laboratory testing, physical examination, vital sign assessments, noting the frequency and types of adverse events. ; ; The expected adverse events related to influenza vaccines are runny nose, nasal congestion, sore throat, chills, loss of appetite, shivers, fatigue, headache, sweating, muscle pain, vomiting, diarrhoea, chest pain, shortness of breath, joint pain. The participant will be asked to record these on a diary for 6 days after the day of dosing and the site staff will also specifically query for these at each visit.[daily for 6 days post vaccination, at site visit on day 30 and as part of the 6 month follow‐up phone call.] SECONDARY OUTCOME: Geometric mean fold increase (GMFI) of anti‐A/Michigan/45/2015 (H1N1) HAI serum antibodies determined 30 days after each vaccination relative to baseline, for each treatment arm[At Day 30 after vaccination.] Geometric mean titres (GMT) of anti‐A/Michigan/45/2015 (H1N1) antibodies (HAI) at Day 0 and Day 30, for each treatment arm. This will be assessed by blood serum assay.[At Day 0 and Day 30 after vaccination.] GMFI within each treatment arm in salivary IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 6 and Day 30 compared to Day 0[At Day 6 and Day 30 after vaccination. ] GMFI within each treatment arm in serum IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0[At Day 30 after vaccination. ] GMFI within each treatment arm in serum IgG antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0[At Day 30 after vaccination. ] The percentage of participants within each treatment arm with a equals 2‐fold rise in salivary IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 6 and Day 30 compared to Day 0[At Day 6 and Day 30 after vaccination.] The percentage of participants within each treatment arm with a equals 2‐fold rise in serum IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0[At Day 30 after vaccination. ] The percentage of participants within each treatment arm with a equals 2‐fold rise in serum IgG antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0[At Day 30 after vaccination. ] The percentage of participants, regardless of sero‐status, within each treatment arm who experience an H1N1 MI/45/2015 specific sero‐response post dose between Day 0 and Day 28 to 35. Sero‐response is defined as a equals 4‐fold rise in HAI titre from baseline. This will be assessed by blood serum assay at day 6 and day 30 as compared to the blood serum assay at baseline (day 0 pre‐dose).[At Day 0 and Day 28‐35 after vaccination.] The percentage of sero‐susceptible participants within each treatment arm who experience an H1N1 MI/45/2015 specific sero‐response post dose between Day 0 and Day 28 to 35. Sero‐response is defined as a equals 4‐fold rise in HAI titre from baseline. Participants with a baseline HAI titre <10 (MI/45/2015) will be considered to be sero‐susceptible for H1N1.