Seroprevalence of HBV and HCV in primary hepatocellular carcinoma patients in Zimbabwe

BACKGROUND:Primary hepatocellular carcinoma (PHC) is one of the most common cancers in Zimbabwe. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are suspected to play a major role in causing this cancer. The objective of this study was to determine the seroprevalence of HBV and HCV in PHC at Parirenyatwa Referral Hospital in Zimbabwe. We evaluated the serological markers of the two viruses in patients with PHC using commercially available enzyme-linked immunosorbent kits. RESULTS: Out of the 60 patients with PHC, 48.3% were seropositive for HBV and 20.0% were seropositive for HCV. Co-infection by HCV and HBV was found in 8% of the patients. Only 13.3% of the health controls (blood donors) were positive for HBV. All the controls were negative for HCV. CONCLUSION: The high seropositivity of HBV and HCV in PHC in Zimbabwe suggested that the two viruses were a major cause of the cancer

Oral vaccination with a recombinant Salmonella vaccine vector provokes systemic HIV-1 subtype C Gag-specific CD4+ Th1 and Th2 cell immune responses in mice

<p>Abstract</p> <p>Background</p> <p>Recombinant <it>Salmonella </it>vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1). The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th) responses in mice after oral immunization with a live attenuated <it>Salmonella </it>vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart) with this recombinant <it>Salmonella</it>. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Mice vaccinated with the recombinant <it>Salmonella </it>elicited both HIV-1-specific Th1 (interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α)) and Th2 (interleukin-4 (IL-4) and interleukin-5 (IL-5)) cytokine responses. The vaccine induced 70 (IFN-γ) spot-forming units (SFUs)/10e6 splenocytes and 238 IL-4 SFUs/10e6 splenocytes. Splenocytes from vaccinated mice also produced high levels of Th1 and Th2 cytokines upon stimulation with a Gag CD4 peptide. The levels of IFN-γ, TNF-α, IL-4 and IL-5 were 7.5-, 29.1-, 26.2- and 89.3-fold above the background, respectively. Both HIV-1 Gag-specific IgG1 and IgG2a antibodies were detected in the sera of vaccinated mice.</p> <p>Conclusion</p> <p>The study highlights the potential of orally-delivered attenuated <it>Salmonella </it>as mucosal vaccine vectors for HIV-1 Subtype C Gag to induce Gag-specific CD4+ Th1 and Th2 cellular immune responses and antibodies which may be important characteristics required for protection against HIV-1 infection.</p

An oral recombinant Salmonella enterica serovar Typhimurium mutant elicits systemic antigen-specific CD8+ T cell cytokine responses in mice

<p>Abstract</p> <p>Background</p> <p>The induction of antigen-specific CD8+ T cell cytokine responses against an attenuated, oral recombinant <it>Salmonella enterica </it>serovar Typhimurium vaccine expressing a green fluorescent protein (GFP) model antigen was investigated. A GFP expression plasmid was constructed in which the <it>gfp </it>gene was fused in-frame with the 5' domain of the <it>Escherichia coli β</it>-galactosidase <it>α</it>-gene fragment with expression under the <it>lac </it>promoter. Groups of mice were orally immunized three times with the bacteria and systemic CD8+ T cell cytokine responses were evaluated.</p> <p>Results</p> <p>High level of the GFP model antigen was expressed by the recombinant <it>Salmonella </it>vaccine vector. Systemic GFP-specific CD8+ T cell cytokine (IFN-γ and IL-4) immune responses were detected after mice were orally vaccinated with the bacteria. It was shown that 226 net IFN-γ and 132 net IL-4 GFP-specific SFUs/10e6 splenocytes were formed in an ELISPOT assay. The level of IFN-γ produced by GFP peptide-stimulated cells was 65.2-fold above background (p < 0.05). The level of IL-4 produced by the cells was 10.4-fold above background (p < 0.05).</p> <p>Conclusion</p> <p>These results suggested that a high expressing recombinant <it>Salmonella </it>vaccine given orally to mice would elicit antigen-specific CD8+ T cell responses in the spleen. <it>Salmonella </it>bacteria may, therefore, be used as potential mucosal vaccine vectors.</p

The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen

Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG) that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP). Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206]) were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]). The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]). Mice primed with 10 7 CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10 6 splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge

Recombinant Salmonella enterica Serovar Typhimurium as a Vaccine Vector for HIV-1 Gag

The HIV/AIDS epidemic remains a global health problem, especially in Sub-Saharan Africa. An effective HIV-1 vaccine is therefore badly required to mitigate this ever-expanding problem. Since HIV-1 infects its host through the mucosal surface, a vaccine for the virus needs to trigger mucosal as well as systemic immune responses. Oral, attenuated recombinant Salmonella vaccines offer this potential of delivering HIV-1 antigens to both the mucosal and systemic compartments of the immune system. So far, a number of pre-clinical studies have been performed, in which HIV-1 Gag, a highly conserved viral antigen possessing both T- and B-cell epitopes, was successfully delivered by recombinant Salmonella vaccines and, in most cases, induced HIV-specific immune responses. In this review, the potential use of Salmonella enterica serovar Typhimurium as a live vaccine vector for HIV-1 Gag is explored

Recombinant Salmonella enterica serovar Typhimurium vaccine vector expressing green fluorescent protein as a model antigen or human immunodeficiency virus type 1 subtype C Gag

Includes bibliographical references (leaves 172-200)