EuroNeut41: Safety & Immunogenicity of Immunisations With HIV Vaccine

Inclusion criteria

• Women aged between 18 and 55 years on the day of screening
• Available for a maximal study duration of 12/13 months from the inclusion
• Willing and able to give written informed consent
• At low risk of HIV infection 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 HIV negative partner
• not had unprotected sex with someone from a region where HIV is more common (e.g Sub-Saharan African, Caribbean, South East Asia) outside a relationship with a regular known HIV negative partner
• Negative HIV 1/2 antibody/antigen test at screening
• If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; use of condoms incorporating spermicide if using these; physiological or anatomical sterility) from 14 days prior to the first vaccination until 6 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination and blood pregnancy test at screening and final follow up.
• Agree, to abstain from medications or other agents that are applied via the nasal route from 24 hours prior to each nasal vaccine dosing through to the safety assessment 1week later
• Agree to abstain from donating blood during their participation in the trial
• Registered with GP and medical history available for 12 months before dosing
• Satisfactory response received from General Practitioner relating to medical history before randomization.

Exclusion criteria

• Pregnant or lactating, or planning to get pregnant within the next year
• Positive alcohol test
• Positive drugs of abuse test
• Clinically relevant abnormality on history or examination:

• central nervous system disorder or disease, including
• history of grand-mal epilepsy
• cranial nerve palsies
• severe eczema
• severe epistaxis requiring surgical intervention or blood transfusion
• clinically significant liver disease
• clinically significant haematological, metabolic, gastrointestinal, renal, psychiatric or cardio-pulmonary disorders
• ongoing infection;
• autoimmune disease, immunodeficiency or use of immunosuppressive agents in preceding 3 months prior to dosing
• using inhaled cortico-steroids and intranasal medications
• Known or suspected history of clinically relevant nasal surgery, injury, nasal polyps or cleft palate, or a condition likely to require regular intranasal medication, which in the opinion of the investigator might interfere with intranasal vaccine administration
• Known hypersensitivity to any component of the vaccine formulations used in this trial or have severe or multiple allergies
• History of severe local or general reaction to vaccination defined as

• local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
• general: fever > 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
• Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of scheduled study vaccine dosing
• Receipt of an experimental vaccine containing HIV envelope proteins at any time in the past
• Receipt of blood products or immunoglobin within 4 months of screening
• Participation in another trial of a medicinal product, completed less than 90 days prior to Visit 2 and planned participation in another clinical trial during the present trial
• HIV 1/2 antibody/antigen positive or indeterminate on screening
• Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
• Clinically significant routine laboratory parameters.
• Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
• Unlikely to comply with protocol
• History of drug or alcohol abuse or regular using of drugs, or who test positive in drugs of abuse and alcohol test at screening or admission
• Has a condition, or is on regular medication (other than paracetamol, multivitamin, E45, or over the counter remedies) which in the opinion of the investigator is not suitable for participation in the study
• Any local vaginal, cervical or gynaecological condition which may interfere with collection or interpretation of data collected through vaginal samples.
• Using any Intra Uterine Contraceptive Device; as there is a risk of dislodging, displacing or removing the device when pulling or removing Softcup used for vaginal sampling.
• Clinically significant abnormality on ECG performed at the screening visit
• Any condition that, in the investigator's opinion, compromises the volunteer's ability to meet protocol requirements or to complete the study.