Investigating a Vaccine Against COVID-19

A phase 2/3 study to determine the efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in healthy UK volunteers.

There will be 12 study groups and it is anticipated that a total of 12,390 volunteers will be enrolled. Groups 1, 7 \& 9 are adults aged 56-69 years; groups 2, 8 \& 10 are adults 70 years and over; groups 4, 5 \& 6 are adults aged 18-55 years; group 11 is adults aged 18-55 years who have previously received a ChAdOx vectored vaccine; group 12 is HIV positive adults aged 18-55 years.

The vaccine will be administered intramuscularly into the deltoid of the non-dominant arm (preferably).

All subjects will undergo follow-up for a total of 1 year post last vaccination. Additional visits or procedures may be performed at the discretion of the investigators, e.g., further medical history and physical examination, or additional blood tests and other investigations if clinically relevant

Eligibility Criteria:
Inclusion Criteria:

* Adults aged 18 - 55 years (groups 4, 5, 6 and 11)
* Adults aged 56-69 years (groups 1, 7, and 9)
* Adults aged 70 years and older (groups 2, 8, and 10)
* 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 and access all medical records when relevant to study procedures.
* For females of childbearing potential only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination.
* Agreement to refrain from blood donation during the course of the study.
* Provide written informed consent.

Additional Inclusion criteria to Group 12 (HIV sub-study):

* HIV positive
* Receiving antiretroviral therapy
* Undetectable HIV viral load
* CD4\>350 cells/mL

Exclusion Criteria:

• Participation in COVID-19 prophylactic drug trials for the duration of the study.

Note: Participation in COVID-19 treatment trials is allowed in the event of hospitalisation due to COVID-19. The COV002 study team should be informed as soon as possible.

• Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study.

Note: Disclosure of serostatus post enrolment may accidently unblind participants to group allocation. Participation in COV002 can only be allowed if volunteers are kept blinded to their serology results from local/national serological surveys

* Receipt of any vaccine (licensed or investigational) other than the study intervention within 30 days before and after each study vaccination, with the exception of the licensed seasonal influenza vaccination and the licensed pneumococcal vaccination. Participants will be encouraged to receive these vaccinations at least 7 days before or after their study vaccine.
* Prior or planned receipt of an investigational or licensed vaccine or product likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). This exclusion criteria will not apply to group 11, as recruitment will be targeted at those volunteers who previously received a ChAdOx1 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 (except group 12, where HIV infected participants are allowed); asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤14 days)
* History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY
* Any history of angioedema.
* Any history of anaphylaxis.
* Pregnancy, lactation or willingness/intention to become pregnant during the study.
* Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
* History of serious psychiatric condition likely to affect participation in the study.
* Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
* Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban)
* Suspected or known current alcohol or drug dependency.
* Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
* Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed)
* History of laboratory confirmed COVID-19 (except groups 5d, 5e, 5f, 9, 10 and 11).
* Seropositivity to SARS-CoV-2 before enrolment (except groups 5d, 5e, 5f, 9, 10 and 11)
* NB: volunteers with previous NAAT positive results are also allowed in groups 9, 10 and 11

Additional Exclusion criteria to Groups 4, 6, 9 and 10

* History of allergic disease or reactions likely to be exacerbated by Paracetamol
* Note: Caution should be taken when recommending paracetamol to adults who already take paracetamol chronically

Re-vaccination exclusion criteria (two-dose groups only)

* Anaphylactic reaction following administration of vaccine
* Pregnancy. An exception to this will be prior to receipt of a booster dose at extra visit B. If a pregnant woman has discussed vaccination with their usual clinician (e.g. GP) and chooses to receive a COVID-19 vaccination, this may be administered by the trial team as part of extra visit B. (Protocol 19.0) or as part of the provision of treatment to controls.
* Any AE that in the opinion of the Investigator may affect the safety of the participant or the interpretation of the study results