Matches in SemOpenAlex for { <https://semopenalex.org/work/W2135294077> ?p ?o ?g. }
- W2135294077 endingPage "3410" @default.
- W2135294077 startingPage "3392" @default.
- W2135294077 abstract "A modified vaccinia virus Ankara poxvirus vector expressing the HIV-1 Env, Gag, Pol, and Nef antigens from clade B (MVA-B) is currently being tested in clinical trials. To improve its immunogenicity, we have generated and characterized the immune profile of MVA-B containing a deletion of the vaccinia viral gene N2L, which codes for an inhibitor of IRF3 (MVA-B ΔN2L). Deletion of N2L had no effect on virus growth kinetics or on the expression of HIV-1 antigens; hence, the N2 protein is not essential for MVA replication. The innate immune responses triggered by MVA-B ΔN2L revealed an increase in beta interferon, proinflammatory cytokines, and chemokines. Mouse prime-boost protocols showed that MVA-B ΔN2L improves the magnitude and polyfunctionality of HIV-1-specific CD4(+) and CD8(+) T cell adaptive and memory immune responses, with most of the HIV-1 responses mediated by CD8(+) T cells. In the memory phase, HIV-1-specific CD8(+) T cells with an effector phenotype were predominant and in a higher percentage with MVA-B ΔN2L than with MVA-B. In both immunization groups, CD4(+) and CD8(+) T cell responses were directed mainly against Env. Furthermore, MVA-B ΔN2L in the memory phase enhanced levels of antibody against Env. For the vector immune responses, MVA-B ΔN2L induced a greater magnitude and polyfunctionality of VACV-specific CD8(+) T memory cells than MVA-B, with an effector phenotype. These results revealed the immunomodulatory role of N2L, whose deletion enhanced the innate immunity and improved the magnitude and quality of HIV-1-specific T cell adaptive and memory immune responses. These findings are relevant for the optimization of poxvirus vectors as vaccines.On the basis of the limited efficacy of the RV144 phase III clinical trial, new optimized poxvirus vectors as vaccines against HIV/AIDS are needed. Here we have generated and characterized a new HIV/AIDS vaccine candidate on the basis of the poxvirus MVA vector expressing HIV-1 Env, Gag, Pol, and Nef antigens (MVA-B) and containing a deletion in the vaccinia virus N2L gene. Our findings revealed the immunomodulatory role of N2L and proved that its deletion from the MVA-B vector triggered an enhanced innate immune response in human macrophages and monocyte-derived dendritic cells. Furthermore, in immunized mice, MVA-B ΔN2L induced improvements in the magnitude and quality of adaptive and memory HIV-1-specific CD4(+) and CD8(+) T cell immune responses, together with an increase in the memory phase of levels of antibody against Env. Thus, the selective deletion of the N2L viral immunomodulatory gene is important for the optimization of MVA vectors as HIV-1 vaccines." @default.
- W2135294077 created "2016-06-24" @default.
- W2135294077 creator A5007117539 @default.
- W2135294077 creator A5030229109 @default.
- W2135294077 creator A5030712042 @default.
- W2135294077 creator A5088143385 @default.
- W2135294077 date "2014-03-15" @default.
- W2135294077 modified "2023-10-13" @default.
- W2135294077 title "Deletion of the Vaccinia Virus N2L Gene Encoding an Inhibitor of IRF3 Improves the Immunogenicity of Modified Vaccinia Virus Ankara Expressing HIV-1 Antigens" @default.
- W2135294077 cites W1520445572 @default.
- W2135294077 cites W1624931691 @default.
- W2135294077 cites W1906664533 @default.
- W2135294077 cites W1945834141 @default.
- W2135294077 cites W1964407118 @default.
- W2135294077 cites W1966903309 @default.
- W2135294077 cites W1969045843 @default.
- W2135294077 cites W1972487217 @default.
- W2135294077 cites W1974433492 @default.
- W2135294077 cites W1977840008 @default.
- W2135294077 cites W1980221962 @default.
- W2135294077 cites W1981480494 @default.
- W2135294077 cites W1984471158 @default.
- W2135294077 cites W1985611744 @default.
- W2135294077 cites W1986059049 @default.
- W2135294077 cites W1990521726 @default.
- W2135294077 cites W1992974476 @default.
- W2135294077 cites W1995300440 @default.
- W2135294077 cites W1996383787 @default.
- W2135294077 cites W2002386257 @default.
- W2135294077 cites W2005018860 @default.
- W2135294077 cites W2005663597 @default.
- W2135294077 cites W2008767788 @default.
- W2135294077 cites W2012298213 @default.
- W2135294077 cites W2014694744 @default.
- W2135294077 cites W2017161741 @default.
- W2135294077 cites W2019923555 @default.
- W2135294077 cites W2023832375 @default.
- W2135294077 cites W2024230991 @default.
- W2135294077 cites W2024364763 @default.
- W2135294077 cites W2026526751 @default.
- W2135294077 cites W2029717255 @default.
- W2135294077 cites W2032141002 @default.
- W2135294077 cites W2032640750 @default.
- W2135294077 cites W2034863440 @default.
- W2135294077 cites W2035167377 @default.
- W2135294077 cites W2036693151 @default.
- W2135294077 cites W2036728549 @default.
- W2135294077 cites W2040878504 @default.
- W2135294077 cites W2047018553 @default.
- W2135294077 cites W2048955142 @default.
- W2135294077 cites W2049788879 @default.
- W2135294077 cites W2051300784 @default.
- W2135294077 cites W2056222019 @default.
- W2135294077 cites W2056718686 @default.
- W2135294077 cites W2056856535 @default.
- W2135294077 cites W2057111361 @default.
- W2135294077 cites W2059505299 @default.
- W2135294077 cites W2062282746 @default.
- W2135294077 cites W2073008794 @default.
- W2135294077 cites W2073372936 @default.
- W2135294077 cites W2075340091 @default.
- W2135294077 cites W2075345074 @default.
- W2135294077 cites W2075928204 @default.
- W2135294077 cites W2076148928 @default.
- W2135294077 cites W2077865764 @default.
- W2135294077 cites W2079084862 @default.
- W2135294077 cites W2080667758 @default.
- W2135294077 cites W2084808899 @default.
- W2135294077 cites W2092627204 @default.
- W2135294077 cites W2093645417 @default.
- W2135294077 cites W2094538816 @default.
- W2135294077 cites W2095662784 @default.
- W2135294077 cites W2096904495 @default.
- W2135294077 cites W2097016524 @default.
- W2135294077 cites W2105323221 @default.
- W2135294077 cites W2107683840 @default.
- W2135294077 cites W2109491705 @default.
- W2135294077 cites W2113847305 @default.
- W2135294077 cites W2116971967 @default.
- W2135294077 cites W2126666403 @default.
- W2135294077 cites W2127265596 @default.
- W2135294077 cites W2131674674 @default.
- W2135294077 cites W2132792285 @default.
- W2135294077 cites W2137766449 @default.
- W2135294077 cites W2140483605 @default.
- W2135294077 cites W2143421242 @default.
- W2135294077 cites W2144575453 @default.
- W2135294077 cites W2145243874 @default.
- W2135294077 cites W2145410013 @default.
- W2135294077 cites W2146671000 @default.
- W2135294077 cites W2146962869 @default.
- W2135294077 cites W2149024166 @default.
- W2135294077 cites W2151026229 @default.
- W2135294077 cites W2152048324 @default.
- W2135294077 cites W2152713507 @default.
- W2135294077 cites W2155345670 @default.
- W2135294077 cites W2156164378 @default.
- W2135294077 cites W2156310736 @default.