Safety & immunogenicity of tgAAC09, a recombinant adeno-associated virus type 2 HIV-1 subtype C vaccine in India.
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BACKGROUND & OBJECTIVES: 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 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. (+info)
Serum hyaluronan and collagen IV as non-invasive markers of liver fibrosis in patients from an endemic area for schistosomiasis mansoni: a field-based study in Brazil.
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Role of Toll-like receptor 4 and human defensin 5 in primary endocervical epithelial cells.
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BACKGROUND: Endocervical epithelial cells play early roles in the defense of upper female genital tract to pathogens. Toll-like receptors (TLRs) and human defensins (HD) have recently been identified as fundamental components of the innate immune responses to bacterial pathogens. We aimed to use in vitro model of human primary endocervical epithelial cells (HPECs) to investigate their roles in innate immune response of the endocervix. METHODS: TLR4 expression and distribution in HPECs and endocervix were investigated by immunofluorescence (IF). Cultured HPECs were divided into lipopolysaccharide (LPS) group which were treated by LPS for 0, 24 and 48 hours, and control group without treatment. At each time point, the levels of HD5, IL-6 and TNF-alpha in supernants were determined by ELISA. TLR4 and HD5 expressions of cells were detected by Western blotting simultaneously. HD5 expression pattern was also compared between the HeLa cell line and HPECs. RESULTS: Endocervix tissue surface and HPECs expressed TLR4. After incubated with LPS, HPECs expressed significantly higher levels of TLR4 than control group, especially after 24 hours (P < 0.01), however decreased after 48 hours with a similar level of TLR4 expression compared with control group. LPS could upregulate the secretion of HD5, IL-6 and TNF-alpha in a time-dependent manner (24 hours: P < 0.05; 48 hours: P < 0.01, compared with control group). Intracellular HD5 expression levels decreased over time. HD5 expression patterns in HPECs were different from HeLa cell line. CONCLUSIONS: To respond to LPS stimulation, HPECs may function in the mucosal immune defense through TLR4 activation and HD5 secretion. HPEC is considered a significant model for immunological study. (+info)
Induction of a cross-reactive CD8(+) T cell response following foot-and-mouth disease virus vaccination.
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A randomized trial of ex vivo CD40L activation of a dendritic cell vaccine in colorectal cancer patients: tumor-specific immune responses are associated with improved survival.
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