Intra- and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials.

The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences.

Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa.

Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.

Methodology/principal Findings: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months.

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

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].

A Phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C-modified vaccinia Ankara virus vaccine candidate in Indian volunteers.

A recombinant modified vaccinia Ankara virus vaccine candidate (TBC-M4) expressing HIV-1 subtype C env, gag, tat-rev, and nef-RT genes was tested in a randomized, double-blind, dose escalation Phase I trial in 32 HIV-uninfected healthy volunteers who received three intramuscular injections of TBC-M4 at 0, 1, and 6 months of 5 x 10(7) plaque-forming units (pfu) (low dosage, LD) (n = 12) or 2.5 x 10(8) pfu (high dosage, HD) (n = 12) or placebo (n = 8). Local and systemic reactogenicity was experienced by approximately 67% and 83% of vaccine recipients, respectively.

Evaluation and recommendations on good clinical laboratory practice guidelines for phase I-III clinical trials.

Marcella Sarzotti-Kelsoe and colleagues harmonize various approaches to Good Clinical Laboratory Practice for clinical trials into a single set of recommendations.

Concordant proficiency in measurement of T-cell immunity in human immunodeficiency virus vaccine clinical trials by peripheral blood mononuclear cell and enzyme-linked immunospot assays in laboratories from three continents.

The gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay is used routinely to evaluate the potency of human immunodeficiency virus (HIV) vaccine candidates and other vaccine candidates. In order to compare candidates and pool data from multiple trial laboratories, validated standardized methods must be applied across laboratories. Proficiency panels are a key part of a comprehensive quality assurance program to monitor inter- and intralaboratory performance, as well as assay performance, over time.

Clinical performance of an in-house real-time RT-PCR assay using a fluorogenic LUX primer for quantitation of human immunodeficiency virus type-1 (HIV-1).

The South African National Antiretroviral Treatment Guideline recommends the use of HIV viral load assays for routine monitoring of HIV-1 positive patients on Highly Active Antiretroviral Therapy (HAART). Approved commercial HIV-1 viral load assays are expensive for developing countries where a large number of patients are treated in the public sector. The evaluation of an in-house HIV-1 viral load assay (LUX assay) is described using 458 plasma specimens.

Fluorogenic LUX primer for quantitation of HIV-1 by real-time RT-PCR.

Measurement of HIV-1 viral load in plasma is an important marker of disease progression and efficacy of antiretroviral therapy. Real-time polymerase chain reaction (PCR) offers an opportunity to develop more affordable alternative viral load assays. This article reports on the development of a novel real-time reverse-transcriptase (RT)-PCR assay for quantitation of HIV-1 RNA copies.

Dried blood spots improve access to HIV diagnosis and care for infants in low-resource settings.

Effective health care delivery to the majority of perinatally exposed infants worldwide, including those enrolled in prevention of mother-to-child transmission programs, is hampered by lack of access to an HIV diagnosis in infancy. Dried blood spot collection from young infants for centralized HIV polymerase chain reaction (PCR) testing is attainable in low-resource settings, provided PCR methodology suitable for routine laboratory service is available. The accuracy of the Roche Amplicor HIV-1 DNA test version 1.

Affordable diagnosis of human immunodeficiency virus infection in infants by p24 antigen detection.

The expense of PCR testing limits diagnosis of HIV infection in infancy in low resource settings. The ultrasensitive p24 antigen assay has been proposed as an accurate substitute; however, its ability to detect different HIV viral subtypes remains to be determined. A sensitivity of 98.