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  1. Article: Assessing vaccine-mediated protection in an ultra-low dose

    Plumlee, C R / Barrett, H W / Shao, D E / Lien, K A / Cross, L M / Cohen, S B / Edlefsen, P T / Urdahl, K B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Despite widespread immunization with Bacille-Calmette-Guerin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack ... ...

    Abstract Despite widespread immunization with Bacille-Calmette-Guerin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack of a robust animal model to assess vaccine efficacy has hindered our ability to prioritize candidates for human clinical trials. Here we use a murine ultra-low dose (ULD)
    Language English
    Publishing date 2023-06-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.22.533820
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

    Hertz, T / Logan, M.G / Rolland, M / Magaret, C.A / Rademeyer, C / Fiore-Gartland, A / Edlefsen, P.T / DeCamp, A / Ahmed, H / Ngandu, N / Larsen, B.B / Frahm, N / Marais, J / Thebus, R / Geraghty, D / Hural, J / Corey, L / Kublin, J / Gray, G /
    McElrath, M.J / Mullins, J.I / Gilbert, P.B / Williamson, C

    Vaccine. 2016 Nov. 11, v. 34, no. 47

    2016  

    Abstract: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated ... ...

    Abstract The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic.A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert.There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively.This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
    Keywords Human immunodeficiency virus 1 ; alleles ; amino acids ; epitopes ; gene frequency ; immune response ; placebos ; vaccines ; viruses
    Language English
    Dates of publication 2016-1111
    Size p. 5792-5801.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2016.09.054
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1930: Show issues Location:
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  3. Article ; Online: A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial.

    Hertz, T / Logan, M G / Rolland, M / Magaret, C A / Rademeyer, C / Fiore-Gartland, A / Edlefsen, P T / DeCamp, A / Ahmed, H / Ngandu, N / Larsen, B B / Frahm, N / Marais, J / Thebus, R / Geraghty, D / Hural, J / Corey, L / Kublin, J / Gray, G /
    McElrath, M J / Mullins, J I / Gilbert, P B / Williamson, C

    Vaccine

    2016  Volume 34, Issue 47, Page(s) 5792–5801

    Abstract: Introduction: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here ... ...

    Abstract Introduction: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic.
    Materials and methods: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert.
    Results: There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively.
    Discussion: This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
    MeSH term(s) AIDS Vaccines/administration & dosage ; AIDS Vaccines/immunology ; Adenoviridae ; Cohort Studies ; Double-Blind Method ; Epitopes/genetics ; Epitopes/immunology ; Female ; Gene Frequency ; HIV Infections/prevention & control ; HIV-1/immunology ; HLA-A2 Antigen/genetics ; HLA-A2 Antigen/immunology ; Humans ; Immunity, Active ; Male ; Sample Size ; Vaccination Coverage ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/immunology ; gag Gene Products, Human Immunodeficiency Virus/genetics ; gag Gene Products, Human Immunodeficiency Virus/immunology ; nef Gene Products, Human Immunodeficiency Virus/genetics ; nef Gene Products, Human Immunodeficiency Virus/immunology ; pol Gene Products, Human Immunodeficiency Virus/genetics ; pol Gene Products, Human Immunodeficiency Virus/immunology
    Chemical Substances AIDS Vaccines ; Epitopes ; HLA-A*02:01 antigen ; HLA-A2 Antigen ; Vaccines, Synthetic ; gag Gene Products, Human Immunodeficiency Virus ; nef Gene Products, Human Immunodeficiency Virus ; pol Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2016-10-15
    Publishing country Netherlands
    Document type Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2016.09.054
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1930: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 458: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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