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

被引:0
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作者
Mehendale, Sanjay [1 ]
Sahay, Seema [1 ]
Thakar, Madhuri [1 ]
Sahasrabuddhe, Sushant [1 ]
Kakade, Meghana [1 ]
Shete, Ashwini [1 ]
Shrotri, Aparna [2 ]
Spentzou, Aggeliki [3 ]
Tarragona, Tony [3 ]
Stevens, Gwynneth [4 ]
Kochhar, Sonali [5 ]
Excler, John Louis [6 ]
Fast, Pat [6 ]
Paranjape, Ramesh [1 ]
机构
[1] Natl AIDS Res Inst ICMR, Pune, Maharashtra, India
[2] Natl AIDS Res Inst, Int AIDS Vaccine Initiat, Pune, Maharashtra, India
[3] Univ London Imperial Coll Sci Technol & Med, HIL, Int AIDS Vaccine Initiat, London SW7 2AZ, England
[4] Int AIDS Vaccine Initiat, Johannesburg, South Africa
[5] Int AIDS Vaccine Initiat India Off, New Delhi, India
[6] Int AIDS Vaccine Initiat, Geneva, Switzerland
关键词
Adeno-associated; clinical trial; HIV candidate vaccine; Phase I; safety; tgAACO9; IMMUNODEFICIENCY-VIRUS; CANARYPOX VACCINE; AIDS; COMBINATION; PUNE; TRANSMISSION; PREVENTION; INFECTION; RESPONSES; CLINICS;
D O I
暂无
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 [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. Interpretation & conclusions: The trial was a benchmark in phase I clinical evaluation of RIV 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.
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页码:168 / 175
页数:8
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