Safety & immunogenicity of tgAAC09, a recombinant adeno-associated virus type 2 HIV-1 subtype C vaccine in India.

Background & objective: A phase 1 trial of adeno-associated virus based HIV-1 subtype C vaccine (tgAAC09) was conducted at two sites in Germany and Belgium and one site in India. This paper reports the safety and immunogenicity of tgAAC09 in healthy adult Indian volunteers. Methods: Between January 2005 and December 2006, 30 consenting volunteers were enrolled in the placebo controlled double-blind dose-escalation trial [3x109, 3x1010 and 3x1011 DNase resistant particles (DRPs)/ml]. Single injection of the candidate vaccine was administered to ten volunteers randomized in 8:2 ratio in vaccine and placebo arms at each dosage level. Results: The mean age of study volunteers (16 men and 14 women) was 34 yr. Six local reactogenicity events and 14 systemic reactogenicity events like malaise, fever, headache and myalgia were reported, both were dose-dependent. The difference between the adverse events reported by vaccine and placebo recipients (79 and 67%) was not significant. A modest IFN-γ ELISPOT response [248 spot forming units (SFU)/million cells] was detected in one volunteer from high dose group and low response (56 and 75 SFU/million cells) in two volunteers in low and mid-dose groups. A post-vaccination dose-dependent increase was observed in anti AAV2 neutralizing titres. None of the volunteers showed a positive antibody response to HIV-1. Interpretation & conclusions: The trial was a benchmark in phase I clinical evaluation of HIV candidate vaccines in India. The vaccine was generally well tolerated and raised no safety concerns. The vaccine was found to be weakly immunogenic. It is essential to understand the role of pre-existing immunity against vectors and significance of evaluation in a prime-boost strategy.

Preparedness for AIDS vaccine trials in India.

India bears a heavy disease burden of HIV/AIDS infected and affected people. A safe, effective and accessible preventive AIDS vaccine, used along with other preventive interventions, is urgently needed to stem the epidemic. This review highlights the extensive preparedness activities undertaken from 2002 by the International AIDS Vaccine Initiative (IAVI), its Indian government and non government partners with the Indian scientific, political, media and community stakeholders and the capacity building process, before the conduct of the first ever AIDS vaccine trials in India in early 2005. Issues addressed included mistrust of clinical research due to past history of some unethical trials, transparency, community involvement, stigma and discrimination, provision for care and treatment of participants, informed consent, gender considerations, approval process, and operational aspects. The strong political support along with preparedness activities led to the successful conduct of AIDS vaccine trials enrolling equitably healthy women and men from all sections of society. This has paved the way for future vaccine trials in the country.