This will be a randomised observational phase 1 study in 48 healthy volunteers aged 18-50. The study is assessing safety and immunogenicity of viral vectored vaccines ChAdOx1 NP+M1 and MVA NP+M1 in heterologous prime-boost regimens. A crossover design will allow comparison of the two vaccines. Volunteers will be divided into 4 groups (n=12 in each group). Groups will be recruited simultaneously to control for seasonal changes in influenza. This is because at certain times of year there is likely to be a higher naturally acquired T cell response to influenza than at other times due to circulating influenza virus in the community.

The study has been extended to include 2 additional groups (group 5 & 6), each containing 12 healthy adults aged 50 years or above. Group 5 will receive ChAdOx 1 NP+M1 on day 0, and group 6 will receive this with an additional boost of MVA-NP+M1 8 weeks later.

Inclusion Criteria for Groups 1-4

The volunteer must satisfy all the following criteria to be eligible for the study:

• Healthy adults aged 18 to 50 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
• For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of vaccination
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent

Exclusion Criteria for Groups 1-4

The volunteer may not enter the study if any of the following apply:

• Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
• Previous receipt of any recombinant adenoviral or recombinant MVA vectored vaccine
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled/topical steroids are allowed)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
• Any history of anaphylaxis in reaction to vaccination
• History of cancer (except basal cell carcinoma and cervical carcinoma in situ)
• History of serious psychiatric condition
• Any chronic illness requiring on-going or awaiting hospital specialist supervision, other than minor surgical procedures and follow up of surgery over 6 months prior to screening
• Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
• Seropositive for hepatitis B surface (HBsAg) or hepatitis C virus (antibodies to HCV)
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• Any other significant disease, disorder or finding (including blood test results), which, in the opinion of the Investigators, would either put the volunteer at risk because of participation in the study, or may influence the result of the study
• No response / confirmation from GP regarding previous medical history

Inclusion Criteria for Groups 5-6

The volunteer must satisfy all the following criteria to be eligible for the study:

• Healthy adults aged 50 or over, no upper age limit
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
• For women of child bearing potential only, willingness to practice continuous effective contraception (i.e. hormonal contraception, intrauterine device or barrier contraception) during the study and a negative urinary pregnancy test on the day(s) of vaccination
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent

Exclusion Criteria for Groups 5-6

The volunteer may not enter the study if any of the following apply:

• Participation in another research study involving an investigational product in the 30 days preceding enrolment, or plans to participate during the study period
• Previous receipt of a vaccine or plans to receive any vaccinations during the study that would interfere with the interpretation of the results of the trial
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled/topical steroids including eye drops and nasal spray/intra-articular steroid injections are allowed)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine including eggs or Kathon (a biocide added to body washes, conditioners, liquid soaps, shampoos and wipes as a preservative)
• Any history of anaphylaxis in reaction to vaccination
• History of treatment for cancer within the preceding six months (except basal cell carcinoma and cervical carcinoma in situ)
• History of serious psychiatric condition
• Any chronic illness requiring on-going or awaiting hospital specialist supervision, other than minor surgical procedures and follow up of surgery over 6 months prior to screening
• Suspected or known injecting drug abuse within the last 5 years
• Alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
• Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (antibodies to HCV) or HIV
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• Any other significant disease, disorder or finding (including blood test results), which, in the opinion of the Investigators, would either put the volunteer at risk because of participation in the study, or may influence the result of the study
• No response / confirmation from GP regarding previous medical history