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RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines

Chang, W L William ; Deere, Jesse D ; Kieu, Hung T ; Castillo, Luis D ; Machmach, Kawthar ; Shen, Xiaoying ; Tomaras, Georgia D ; Shacklett, Barbara L ; Barry, Peter A ; Hartigan-O'Connor, Dennis J ; Sparger, Ellen E

Scientific reports, 2020-08, Vol.10 (1), p.14056-14056, Article 14056 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines
Autor: Chang, W L William ; Deere, Jesse D ; Kieu, Hung T ; Castillo, Luis D ; Machmach, Kawthar ; Shen, Xiaoying ; Tomaras, Georgia D ; Shacklett, Barbara L ; Barry, Peter A ; Hartigan-O'Connor, Dennis J ; Sparger, Ellen E
Assuntos: Adjuvants, Immunologic - pharmacology ; Animals ; Antibodies, Viral - biosynthesis ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Combined vaccines ; Cytomegalovirus - immunology ; Cytomegalovirus - isolation & purification ; Flagellin ; Gag protein ; Gene Products, gag - immunology ; Humans ; Immune clearance ; Immune response ; Immunity, Innate ; Immunogenicity ; Inflammation ; Interferon-gamma - metabolism ; Macaca mulatta ; Major histocompatibility complex ; Primates ; Simian Immunodeficiency Virus - immunology ; Simian Immunodeficiency Virus - isolation & purification ; TLR5 protein ; Toll-like receptors ; Vaccine efficacy ; Vaccines ; Viral Load ; Viral Vaccines - immunology ; Viremia
É parte de: Scientific reports, 2020-08, Vol.10 (1), p.14056-14056, Article 14056
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Rhesus cytomegalovirus (RhCMV) strain 68-1-vectored simian immunodeficiency virus (RhCMV/SIV) vaccines are associated with complete clearance of pathogenic SIV challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type RhCMV. This report presents the first investigation of RhCMV/SIV vaccines in RhCMV-seronegative macaques lacking anti-vector immunity. Fifty percent of rhesus macaques (RM) vaccinated with a combined RhCMV-Gag, -Env, and -Retanef (RTN) vaccine controlled pathogenic SIV challenge despite high peak viremia. However, kinetics of viral load control by vaccinated RM were considerably delayed compared to previous reports. Impact of a TLR5 agonist (flagellin; FliC) on vaccine efficacy and immunogenicity was also examined. An altered vaccine regimen containing an SIV Gag-FliC fusion antigen instead of Gag was significantly less immunogenic and resulted in reduced protection. Notably, RhCMV-Gag and RhCMV-Env vaccines elicited anti-Gag and anti-Env antibodies in RhCMV-seronegative RM, an unexpected contrast to vaccination of RhCMV-seropositive RM. These findings confirm that RhCMV-vectored SIV vaccines significantly protect against SIV pathogenesis. However, pre-existing vector immunity and a pro-inflammatory vaccine adjuvant may influence RhCMV/SIV vaccine immunogenicity and efficacy. Future investigation of the impact of pre-existing anti-vector immune responses on protective immunity conferred by this vaccine platform is warranted.
Editor: England: Nature Publishing Group
Idioma: Inglês

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RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines

Chang, W L William ; Deere, Jesse D ; Kieu, Hung T ; Castillo, Luis D ; Machmach, Kawthar ; Shen, Xiaoying ; Tomaras, Georgia D ; Shacklett, Barbara L ; Barry, Peter A ; Hartigan-O'Connor, Dennis J ; Sparger, Ellen E

England: Nature Publishing Group

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