The multidimensional legal nature of personal genomic sequence data: A South African perspective.

This article provides a comprehensive analysis of the various dimensions in South African law applicable to personal genomic sequence data. This analysis includes property rights, personality rights, and intellectual property rights. Importantly, the under-investigated question of whether personal genomic sequence data are capable of being owned is investigated and answered affirmatively.

Broad, high-magnitude and multifunctional CD4+ and CD8+ T-cell responses elicited by a DNA and modified vaccinia Ankara vaccine containing human immunodeficiency virus type 1 subtype C genes in baboons.

Candidate human immunodeficiency virus (HIV) vaccine regimens based on DNA boosted with recombinant modified vaccinia Ankara (MVA) have been in development for some time, and there is evidence for improved immunogenicity of newly developed constructs. This study describes immune responses to candidate DNA and MVA vaccines expressing multiple genes (gag, RT, tat, nef and env) from HIV-1 subtype C in chacma baboons (Papio ursinus). The vaccine regimen induced (i) strong T-cell responses, with a median of 4103 spot forming units per 10(6) peripheral blood mononuclear cells by gamma interferon (IFN-gamma) ELISPOT, (ii) broad T-cell responses targeting all five vaccine-expressed genes, with a median of 12 peptides targeted per animal and without any single protein dominating the response, (iii) balanced CD4(+) and CD8(+) responses, which produced both IFN-gamma and interleukin (IL)-2, including IL-2-only responses not detected by the ELISPOT assay, (iv) vaccine memory, which persisted 1 year after immunization and could be boosted further, despite strong anti-vector responses, and (v) mucosal T-cell responses in iliac and mesenteric lymph nodes in two animals tested.

HIV-1 subtype C Pr55gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine.

A DNA vaccine expressing human immunodeficiency virus type 1 (HIV-1) southern African subtype C Gag (pTHGag) and a recombinant baculovirus Pr55gag virus-like particle prepared using a subtype C Pr55gag protein (Gag VLP) was tested in a prime-boost inoculation regimen in Chacma baboons. The response of five baboons to Gag peptides in a gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay after three pTHGag immunizations ranged from 100 to 515 spot-forming units (s.f.

A multigene HIV type 1 subtype C modified vaccinia Ankara (MVA) vaccine efficiently boosts immune responses to a DNA vaccine in mice.

Heterologous prime-boost vaccine strategies have generated high frequencies of antigen-specific T cells in preclinical and clinical trials of candidate HIV vaccines. We have developed a DNA (SAAVI DNA-C) and MVA (SAAVI MVA-C) vaccine based on HIV-1 subtype C for testing in clinical trials. Both vaccines contain five subtype C genes: gag, reverse transcriptase, tat, and nef, expressed as a polyprotein, and a truncated env (gp150).

Construction, characterization, and immunogenicity of a multigene modified vaccinia Ankara (MVA) vaccine based on HIV type 1 subtype C.

Candidate vaccines composed of a DNA construct to prime the immune system, followed by modified vaccinia Ankara (MVA) containing matching genes as a booster vaccination, have produced encouraging immune responses in human volunteers. This study presents the detailed construction and characterization of a recombinant MVA that will be tested in combination with a DNA vaccine in Phase I clinical trials in South Africa and the United States. To match recently transmitted viruses in the southern African region and to maximize epitope coverage, the vaccines were constructed to contain five HIV-1 subtype C genes, namely gag, reverse transcriptase, tat, and nef (grttn), expressed as a polyprotein, and a truncated env (gp150).

HIV type 1 subtype C gag and nef diversity in Southern Africa.

Several HIV-1 subtype C-specific gag- and/or nef-based vaccines are currently intended for clinical trial in southern Africa. Here we provide sequences of 64 gag and 45 nef genes sampled in Malawi, Zambia, Zimbabwe, and South Africa and assess the degree of southern African HIV-1 diversity that will confront these vaccines. Whereas reasonable phylogenetic evidence exists for geographical clustering of subtype C gag and nef sequences from various other parts of the world, there is little evidence of similar population founder effects in the southern African epidemic.

Design and preclinical evaluation of a multigene human immunodeficiency virus type 1 subtype C DNA vaccine for clinical trial.

In this study, the design and preclinical development of a multigene human immunodeficiency virus type 1 (HIV-1) subtype C DNA vaccine are described, developed as part of the South African AIDS Vaccine Initiative (SAAVI). Genetic variation remains a major obstacle in the development of an HIV-1 vaccine and recent strategies have focused on constructing vaccines based on the subtypes dominant in the developing world, where the epidemic is most severe. The vaccine, SAAVI DNA-C, contains an equimolar mixture of two plasmids, pTHr.

Heterosexual transmission of multiple highly conserved viral variants in HIV-1 subtype C-infected seronegative women.

Viral population diversity was assessed in samples collected from five HIV-infected women who were RNA positive and antibody negative. Similar to studies in men, highly conserved viral variants were detected (mean nucleotide diversity of 0.11% for p17p24, 0.

Human immunodeficiency virus type 1 subtype C Gag virus-like particle boost substantially improves the immune response to a subtype C gag DNA vaccine in mice.

Human immunodeficiency virus type 1 (HIV-1) subtype C is the predominant HIV in southern Africa, and is the target of a number of recent vaccine candidates. It has been proposed that a heterologous prime/boost vaccination strategy may result in stronger, broader and more prolonged immune responses. Since HIV-1 Gag Pr55 polyprotein can assemble into virus-like particles (VLPs) which have been shown to induce a strong cellular immune response in animals, we showed that a typical southern African subtype C Pr55 protein expressed in insect cells via recombinant baculovirus could form VLPs.

Construction and characterisation of a candidate HIV-1 subtype C DNA vaccine for South Africa.

A candidate DNA vaccine pTHgagC expressing the immunodeficiency virus-1 (HIV-1) gag gene from South African isolate Du422 was constructed and characterised. The isolate was selected on the basis of being the closest to the South African subtype C consensus sequence. Sequence analysis of cytotoxic T lymphocyte (CTL) epitopes showed that HIV subtype C-infected individuals have CTL responses to a number of epitopes present in the vaccine, but also revealed a more limited presence of subtype A- and any B-derived epitopes.

Characterization and selection of HIV-1 subtype C isolates for use in vaccine development.

HIV-1 genetic diversity among circulating strains presents a major challenge for HIV-1 vaccine development, particularly for developing countries where less sequence information is available. To identify representative viruses for inclusion in candidate vaccines targeted for South Africa, we applied an efficient sequence survey strategy to samples from recently and chronically infected persons residing in potential vaccine trial sites. All 111 sequences were subtype C, including 30 partial gag, 26 partial pol, 27 V2-V3 env, and 28 V5-partial gp41 sequences.