Safety and Immunogenicity of Influenza H9 Vaccine in Humans

A double-blind, single centre comparative study in which fourteen groups of 40 male and female adults >18 years of age will be randomly allocated to receive 1.7, 5, 15 or 45 µg quantities of whole virion (WV), Aluminium -adjuvanted WV(Al-WV), and virosomal (V) influenza A/Hong Kong/1073/99 (H9N2) vaccines by intramuscular injection into the deltoid muscle; or 5 or 15microg WV vaccine administered by intradermal injection. A second dose of the same vaccine containing the same quantity of antigen as in the first dose will be administered 21 days later. Subjects will be observed for local and systemic reactions for 30 minutes after each immunisation (day 0 and 21), and will be monitored for any reactions and other adverse events for 7 days after immunisation. Blood for immunogenicity studies will be obtained at day 0 (pre-immunisation), day-21 (+4 days), and at day-42 (i.e., 21 +4 days after the second immunization). Immunogenicity will be evaluated by haemagglutination inhibition, virus neutralization,, single radial haemolysis, neuraminidase inhibition and cellular mediated responses (in a subset of 5-10 subjects from each group).

Inclusion criteria

• Mentally competent adults, who have signed an informed consent form after having received a detailed explanation of the study protocol.
• Male or female subjects over 18 years who are either healthy or have a stable medical condition.
• Able to understand and comply with all study procedures and to complete study diaries
• Individuals who can be contacted throughout the study and are available for all study visits
• Females should either be using secure contraceptive precautions including a) the oral contraceptive pill, b) condom/barrier contraception c) partner has had a vasectomy, d) be surgically sterilised, or e) post- (defined as at least two years since the last menstrual period)

Exclusion criteria

• Any clinically significant concurrent illness or unstable medical condition including: malignant tumours, autoimmune illnesses (including rheumatoid arthritis), acute or progressive renal or hepatic pathology, chronic obstructive pulmonary disease requiring oxygen therapy, and any active neurological disorder.
• Individuals with a history of anaphylaxis or serious reactions to vaccines; hypersensitivity to eggs, chicken protein, chicken feathers, influenzal viral protein, neomycin or polymixin, or products containing mercury.
• Persons with known immunosuppressive disease or who use systemic immunosuppressive drugs or other drugs listed in section 8 of the British National Formulary (BNF) or chloroquine, gold or penicillamine or other drugs listed in section 10.1.3 of the BNF to suppress a chronic disease process, or have received in the last 6 months radiotherapy or chemotherapy.
• Subjects who are at high risk of developing illnesses of the immune system.
• Individuals who are taking immunostimulant therapy or interferon
• Individuals who have received blood products or immunoglobulins parenterally during the preceding three months.
• Women should not be pregnant or lactating.
• Women who refuse to use a reliable contraceptive method throughout the study
• Known or suspected drug abuse.
• Individuals who have received another vaccine or experimental (investigational) drug in the preceding 4 weeks.
• Individuals who have previously received H9N2 vaccine
• Unable to lead an independent life either physically or mentally
• Regularly drink more than 40 units of alcohol weekly
• Individuals who have had acute respiratory pathology or infections requiring systemic antibiotic or antiviral therapy during the preceding 7 days (chronic antibiotic therapy for prevention of urinary tract infections is acceptable).
• Individuals who had a temperature over 38 degrees C in the preceding 3 days.
• Individuals who, in the opinion of the investigator, have conditions that might complicate interpretation of the study results.