study to compare the immunogenicity and safety of two hiv preventive vaccinations in healthy volunteers

Conditions: HIV Infections

Summary: the purpose of the trial is to evaluate the effect upon immune system of two regimens of preventive hiv vaccination in healthy adult volunteers. volunteers will be vaccinated by dna-c and nyvac-c vaccines, and the immune changes will be assessed, as well as safety of the vaccines. volunteers will be followed during 72 weeks.

methods: randomised phase i/ii international trial with a parallel group design, open to participants and investigators but blind to laboratory personnel, in healthy volunteers. vaccines strategies: 70 volunteers will receive 3 dna-c vaccinations and 1 nyvac-c vaccination; 70 volunteers will receive 2 dna-c vaccinations and 2 nyvac-c vaccination. dna-c: 2x2ml intra muscular in right and left vastus lateralis; nyvac-c: 1 ml intramuscular in non-dominant deltoid. main outcome: 1. the presence of cd8/cd4+ t cell responses defined according to internationally agreed criteria for evaluation of ifngamma elispot assays: * in response to env plus at least one of the gag, pol, nef peptide pools, * at weeks 26 or 28; 2. the safety parameters. secondary outcomes: * cellular responses, * antibody responses, * all grade 1 and 2 adverse events, * all events including those considered unrelated. sample size: 140 volunteers enrollment period: 9 months patient's participation duration: 78 weeks study duration: 27 months

Eligibility criteria:
inclusion criteria: * age between 18 and 55 years on the day of screening * available for follow-up for the duration of the study (78 weeks from screening) * able to give written informed consent * at low risk of hiv and willing to remain so for the duration of the study low risk of hiv infection 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 * willing to undergo a hiv test * willing to undergo a genital infection screen * if heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; iucd; 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 * 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 * for french volunteers only : * subjects registered in french health ministry computerised file and authorised to participate in a clinical trial * subjects covered by health insurance * subjects included in the anrs vaccine research network of volunteers exclusion criteria: * pregnant or lactating * clinically relevant abnormality on history or examination including history of grand-mal epilepsy; severe eczema; allergy to eggs or gentamicin; severe allergic diseases; liver disease with inadequate hepatic function; haematological, metabolic or gastrointestinal disorders; uncontrolled infection; autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months * receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment * receipt of blood products or immunoglobin within 4 months of screening * participation in another trial of a medicinal product, completed less than 30 days prior to enrolment * history of severe local or general reaction to vaccination defined as * local: extensive, indurated redness and swelling involving most of the anterolateral thigh or the major circumference of the arm, not resolving within 72 hours * general: fever \>= 39.5oc within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours * hiv 1/2 positive or indeterminate on screening * positive for hepatitis b surface antigen, hepatitis c antibody or serology indicating active syphilis requiring treatment * positive for dna/ana antibodies at titre considered clinically relevant by immunology laboratory * grade 1 or above routine laboratory parameters (see section 4.1.4 \& appendix 4 for definitions) note of clarification 18th april 2008: hyperbilirubinemia has to be considered as an exclusion criterion only when confirmed to be conjugated bilirubinemia * unlikely to comply with protocol

Keywords: aids vaccines vaccines, dna hiv preventive vaccine hiv seronegativity