Enrollments were suspended due to delta-V2 Env unavailability, following the EMA/CHMP/BWP/534898/2008 guideline, not allowing the use of a retest date

This Phase I study was directed at evaluating the safety profile and the immunogenicity of the vaccination with recombinant HIV-1 Tat and V2-deleted Env (delta-V2 Env) proteins administered in association in healthy, immunologically competent adults, compared to delta-V2 Env or Tat alone.

Since the inexorable spreading of HIV pandemic is unabated, the urgency of designing an effective, safe, inexpensive and easily administrable vaccine to protect people from HIV and/or AIDS is an absolute priority. Considering the array of functions sequentially exerted by the regulatory and the structural gene products in supporting the setting of a primary HIV infection, it is expected that vaccines combining early and late viral products (combined vaccines) should be superior to the single antigens approaches since they target multiple viral proteins which are necessary at different key steps of the virus life cycle, including cell-to-cell virus transmission and systemic virus propagation. A combined vaccine strategy based on the early regulatory protein Tat in association with the late structural protein Env modified to increase its immunogenicity (delta-V2Env) has been evaluated in pre-clinical studies in both small animals and monkeys. The results of these studies indicated that the combination of Tat with delta-V2Env is superior in inducing specific immune responses against both Tat and delta-V2Env antigens and in protecting or containing virus replication more efficiently than vaccination with the single antigens alone, confirming that these proteins represent optimal co-antigens for a combined vaccine strategy.

This study was a multicentric, open label, randomized phase I trial, directed to qualify the safety and the immunogenicity of the vaccine based on the association of HIV-1 biologically active Tat and oligomeric ΔV2 Env proteins in healthy, immunologically competent adult volunteers, compared to the single compounds. Tat and delta-V2 Env proteins either in association or as single compounds were administered by a prime-boost regimen, consisting of 3 intradermal priming doses followed by 2 intramuscular boosting injections. Of note, phase I trials have already been successfully conducted with the 2 single components, at the doses proposed in this trial, in healthy individuals.

Inclusion Criteria:

1. Age: 18 to 55 years;
2. Negative blood pregnancy test for women of childbearing potential at screening evaluation (a urine dipstick test will be repeated just before each vaccination), and use of an acceptable mean of contraception by both men and women, since one month prior to immunization (only for women) and until at least 6 months after the last immunization;
3. Blood pressure, heart rate and ECG within normal ranges or with mild alterations acknowledged as non clinically significant by the site clinician;
4. Haematological and biochemical parameters within the clinical site normal ranges or with mild alterations acknowledged by the site clinician as non clinically significant;
5. Normal urine dipstick with esterase and nitrite;
6. Normal thyroid function;
7. Negative for HIV infection and for anti-Tat antibodies;
8. Good physical and mental health status;
9. Availability for the planned study duration;
10. Signed informed consent.

Exclusion Criteria:

1. Concomitant neoplastic diseases;
2. History of malignant neoplastic diseases;
3. History of encephalopathy, neuropathy or unstable CNS pathology, immunodeficiency, autoimmune disease, angina or cardiac arrhythmias, or any other clinically significant medical problems;
4. History of anaphylaxis or serious adverse reactions to vaccines as well as serum IgE levels exceeding 1,000 U.I./mL;
5. History of serious allergic reaction to any substance, requiring hospitalization or emergency medical care;
6. Chest radiography showing evidence of active or acute cardiac or pulmonary disease;
7. Any unstable cardiovascular disease;
8. Active syphilis by TPHA and RPR tests [NOTE: If the serology is documented to be a false positive or due to an adequately treated infection, the volunteer is eligible];
9. Active tuberculosis by cutaneous TB diagnostic test [NOTE: Volunteers with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring specific therapy are eligible];
10. Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol. Persons with psychotic disorders, major affective disorders or suicidal ideation are specifically excluded;
11. Current use of psychotropic drugs;
12. Drug and/or alcohol abuse;
13. Current or prior therapy with immunomodulators or immunosuppressive drugs and anticoagulant drugs within 30 days prior to study medication administration;
14. Live attenuated vaccines within 60 days prior to study entry [NOTE: Medically indicated sub-unit or killed vaccines (e.g, influenza, pneumococcal, hepatitis A and B) are not exclusionary, but should be given at least 4 weeks away from anti-HIV immunizations];
15. Use of investigational agents within 90 days prior to study entry;
16. Participation in another experimental protocol within 6 months prior to pre-study screening;
17. Prior receipt of HIV vaccine in a previous HIV vaccine trial;
18. Receipt of blood products or immunoglobulin in the past 6 months;
19. Pregnant or lactating women.