ABSTRACT
The drawbacks of conventional inactivated Foot and Mouth Disease (FMD) vaccine, such as escaping of the virus during manufacture processes prompted researchers to explore novel types of vaccine to overcome these disadvantages. Listeria ivanovii (LI) is an intracellular microorganism that possesses immune-stimulatory properties, making it appropriate for use as a live bacterial vaccine vector. The Foot and mouth disease virus (FMDV) VP1 protein is the most immunogenic part of FMDV capsid, it has most of the antigenic sites for viral neutralization. The expression of antigen gene cassette in vitro was confirmed by Western blot analysis. Mice were able to eliminate LIâ³actAplcB-vp1 from the liver and spleen within few days revealed a safety of the candidate vaccine. Two doses of LIâ³actAplcB-vp1 with 14 days of interval were injected into mice. High levels of specific IgG antibodies and CD8+ and CD4+ T cells secreted cytokines including IFN-γ, TNF-α and IL-2 against FMDV-VP1 were achieved. Based on the obtained results, LIâ³actAplcB-vp1 candidate vaccine utilizing Listeria ivanovii as a live vector-based vaccine could enhance a specific cellular and humoral immune responses against the inserted FMDV-vp1 heterologous genes. LIâ³actAplcB-vp1 candidate vaccine could be a modern tool to overcome the disadvantages of the traditional inactivated FMD vaccine.
Subject(s)
Capsid Proteins/immunology , Foot-and-Mouth Disease/prevention & control , Listeria/genetics , Viral Vaccines/immunology , Animals , Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Capsid Proteins/genetics , Cytokines/immunology , Female , Foot-and-Mouth Disease Virus , Immunoglobulin G/blood , Mice , Mice, Inbred C57BL , Vaccines, DNA/immunology , Vaccines, Live, Unattenuated/genetics , Vaccines, Live, Unattenuated/immunology , Viral Vaccines/geneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the drug resistance of HIV patients to the HIV-1 CRF01_AE and CRF07_BC strains in Sichuan province during 2010 to 2013.</p><p><b>METHODS</b>1.5 ml of plasma were collected from AIDS patients who had been receiving anti-retroviral treatment for over 6 months but still had a HIV-1 virus load of over 1 000 copies/ml from January 1, 2010 to December 31, 2013 in Sichuan province. Genetic analysis of the HIV-1 pol gene was performed using self-established method, and patients with a positive drug-resistant HIV-1 pol gene mutation were included. HIV-1 poly gene was successfully sequenced for a total of 1 213 patients. Drug resistance of different HIV-1 strains was compared with χ2 test or Fisher exact test.</p><p><b>RESULTS</b>558 cases (46.0%) of the 1 213 successfully sequenced patients were infected by HIV-1-strains with drug-resistant mutations, including 327 cases (58.6%) infected by CRF01_AE strain, 126 (22.6%) by CRF07_BC strain, 46 (8.2%) by CRF08_BC strain, 33 (5.9%) by B strain, 4 (0.7%) by C strain, 1 (0.2%) by CRF02_AG strain, and 21 (3.8%) by unidentified strains. Drug-resistant mutation analysis revealed that L33, F116, L74, Q151, and T69 resistance mutations occurred only in the CRF01_AE strain, while A71, K43, and Q58 resistance mutations occurred only in the CRF07_BC strain; in nuclear nucleoside reverse transcriptase inhibitors (NRTIs) and non nucleoside reverse transcriptase inhibitors (NNRTIs), CRF01_AE subtype strains showed highly resistant rate were higher than CRF07_BC, CRF08_BC and B subtype strains, with the differences were statistically significant (P<0.05).</p><p><b>CONCLUSION</b>The drug-resistant HIV-1 strains in Sichuan mainly included the CRF01_AE and CRF07_BC strains, which had different resistance mutations.</p>