title: Safety & immunogenicity of tgAAC09, a recombinant adeno-associated virus type 2 HIV-1 subtype C vaccine in India.
abstract: 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 [3x10(9), 3x10(10) and 3x10(11) 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-gamma 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.
  
  
  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.
authors: National AIDS Research Institute (ICMR), Pune, India. smehendale@nariindia.org
authors: Sanjay
authors: S
authors: Mehendale
authors: Seema
authors: S
authors: Sahay
authors: Madhuri
authors: M
authors: Thakar
authors: Sushant
authors: S
authors: Sahasrabuddhe
authors: Meghana
authors: M
authors: Kakade
authors: Ashwini
authors: A
authors: Shete
authors: Aparna
authors: A
authors: Shrotri
authors: Aggeliki
authors: A
authors: Spentzou
authors: Tony
authors: T
authors: Tarragona
authors: Gwynneth
authors: G
authors: Stevens
authors: Sonali
authors: S
authors: Kochhar
authors: John Louis
authors: JL
authors: Excler
authors: Pat
authors: P
authors: Fast
authors: Ramesh
authors: R
authors: Paranjape
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D000229:Dependovirus / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007194:India; D008297:Male; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D014614:Vaccines, Synthetic