Investigating Immunisation Strategies of DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses (UKHVCSpoke003)

Inclusion Criteria:

1. Man or woman aged between 18 and 45 years on the day of screening
2. Available for follow-up for the duration of the study (up to ~10 months from enrolment)

3. At low risk of HIV and willing to remain so for the duration of the study defined as:

   • no history of injecting drug use in the previous ten years
   • no gonorrhoea or syphilis in the last six months
   • no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
   • no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
   • no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
4. Willing to undergo an HIV test
5. Willing to undergo a genital infection screen if indicated by sexual history
6. If heterosexually active female, using an effective method of contraception with partner other than an IUCD/IUS (combined oral contraceptive pill; injectable or implanted contraceptive; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
7. If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
8. Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
9. Registered with a general practitioner (GP) for at least the past three months
10. Satisfactory response received from GP before randomisation
11. Willing and able to give written informed consent

Exclusion Criteria:

1. Pregnant or lactating
2. Presence of an IUCD (intrauterine contraceptive device)/IUS (intrauterine system)

3. Clinically relevant abnormality on history or examination including

   • history of grand-mal epilepsy, seizure disorder or any history of prior seizure
   • severe eczema
   • liver disease with inadequate hepatic function
   • any skin condition which may interfere with the trial assessment on the injection site
   • haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
   • uncontrolled infection; toxic shock syndrome; autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months
4. Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents

5. History of severe local or general reaction to vaccination defined as

   1. local: extensive, indurated redness and swelling involving the major circumference of the arm, not resolving within 72 hours
   2. general: fever >= 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
6. Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment
7. Receipt of an experimental vaccine containing HIV antigens at any time in the past
8. Receipt of blood products or immunoglobin within 4 months of screening
9. Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment
10. HIV 1 or 2 positive or indeterminate on screening
11. Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
12. Grade 1 or above routine laboratory parameters. Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia
13. Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
14. Unlikely to comply with protocol