DNA immunization site determines the level of gene expression and the magnitude, but not the type of the induced immune response
Petkov S., Starodubova E., Latanova A., Kilpeläinen A., Latyshev O., Svirskis S., Wahren B., Chiodi F., Gordejchuk I. V., Isaguliants M.
PLoS ONE
Vol.13, Issue6, Num.e0197902
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1371/journal.pone.0197902
Аннотация:
Optimization of DNA vaccine delivery improves the potency of the immune response and is crucial to clinical success. Here, we inquired how such optimization impacts the magnitude of the response, its specificity and type. BALB/c mice were DNA-immunized with two model immunogens, HIV-1 protease and reverse transcriptase by intramuscular or intradermal injections with electroporation. DNA immunogens were co-delivered with DNA encoding luciferase. Delivery and expression were monitored by in vivo bioluminescence imaging (BLI). The endpoint immune responses were assessed by IFN-γ/IL-2 FluoroSpot, multiparametric flow cytometry and antibody ELISA. Expression and immunogenicity were compared in relation to the delivery route. Regardless of the route, protease generated mainly IFN-γ, and reverse transcriptase, IL-2 and antibody response. BLI of mice immunized with protease- or reverse transcriptase/reporter plasmid mixtures, demonstrated significant loss of luminescence over time. The rate of
Ключевые слова:
gamma interferon; interleukin 2; RNA directed DNA polymerase; cytokine; DNA vaccine; epitope; Human immunodeficiency virus proteinase; p16 protease, Human immunodeficiency virus 1; virus antibody; animal cell; animal tissue; antibody response; Article; bioluminescence; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; DNA immunization; enzyme linked immunosorbent assay; female; flow cytometry; gene expression profiling; immunogenicity; in vitro study; in vivo study; limit of quantitation; mouse; nonhuman; animal; Bagg albino mouse; gene expression; genetics; immunization; immunology; intracellular space; metabolism; muscle; skin; Animals; Antibodies, Viral; Cytokines; Epitopes; Female; Gene Expression; HIV Protease; Immunization; Intracellular Space; Mice; Mice, Inbred BALB C; Muscles; Skin; Vaccines, DNA
Язык текста: Английский
ISSN: 1932-6203
Petkov S.
Starodubova E.
Latanova A.
Kilpeläinen A.
Latyshev O.
Svirskis S.
Wahren B.
Chiodi F.
Gordejchuk I. V. Il`ya Vladimirovich 1984-
Isaguliants M.
Петков С.
Стародубова Е.
Латанова А.
Килпелäинен А.
Латyшев О.
Свирскис С.
Wахрен Б.
Чиоди Ф.
Гордейчук И. В. Илья Владимирович 1984-
Исагулианц М.
DNA immunization site determines the level of gene expression and the magnitude, but not the type of the induced immune response
Текст визуальный непосредственный
PLoS ONE
Vol.13, Issue6 Num.e0197902
2018
Статья
gamma interferon interleukin 2 RNA directed DNA polymerase cytokine DNA vaccine epitope Human immunodeficiency virus proteinase p16 protease, Human immunodeficiency virus 1 virus antibody animal cell animal tissue antibody response Article bioluminescence CD4+ T lymphocyte CD8+ T lymphocyte controlled study DNA immunization enzyme linked immunosorbent assay female flow cytometry gene expression profiling immunogenicity in vitro study in vivo study limit of quantitation mouse nonhuman animal Bagg albino mouse gene expression genetics immunization immunology intracellular space metabolism muscle skin Animals Antibodies, Viral Cytokines Epitopes Female Gene Expression HIV Protease Immunization Intracellular Space Mice Mice, Inbred BALB C Muscles Skin Vaccines, DNA
Optimization of DNA vaccine delivery improves the potency of the immune response and is crucial to clinical success. Here, we inquired how such optimization impacts the magnitude of the response, its specificity and type. BALB/c mice were DNA-immunized with two model immunogens, HIV-1 protease and reverse transcriptase by intramuscular or intradermal injections with electroporation. DNA immunogens were co-delivered with DNA encoding luciferase. Delivery and expression were monitored by in vivo bioluminescence imaging (BLI). The endpoint immune responses were assessed by IFN-γ/IL-2 FluoroSpot, multiparametric flow cytometry and antibody ELISA. Expression and immunogenicity were compared in relation to the delivery route. Regardless of the route, protease generated mainly IFN-γ, and reverse transcriptase, IL-2 and antibody response. BLI of mice immunized with protease- or reverse transcriptase/reporter plasmid mixtures, demonstrated significant loss of luminescence over time. The rate of