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  • 1
    Online Resource
    Online Resource
    Genetic and infectious regulators of baseline and acute immunity across ancestrally distinct human populations
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 1_Supplement ( 2020-05-01), p. 225.1-225.1
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 225.1-225.1
    Abstract: Studies have identified genetic, viral, and immunological associations with the quality of anti-influenza immunity and/or influenza disease severity, however, there has not been an integrative analysis of these factors, both at baseline and during acute infection. Using samples from healthy or flu infected human cohorts across 5 countries, we found that herpesviruses (HVs) have unique and interactive effects on cytokine levels specific to anatomic location during flu infection. Similar cytokine associations were also observed in healthy controls. Additionally, HV infection is also associated with decreased flu severity and virus shedding, and increased antibody titers. Associations between cytokine levels and flu severity were consistent in cohorts of similar ancestral and environmental backgrounds, however unique correlates were observed in populations from distinct backgrounds. Further, we identified ~100 variants in immune related genes either enriched in or absent from a given ancestral population, a portion of which are eQTLs at baseline, supporting the potential of host genetics to impact immune variation. Ongoing work focuses on assessing which SNPs are eQTLs in response to bacterial and viral TLR agonists. Ancestry informative marker PCA values and eQTLs will be included in the statistical models to account for the collective effects of infectious, biological, and genetic factors. These results will provide insight into which factors predominantly affect a given immune measure and how this contributes to immune competence and variation across distinct populations. Understanding these interactions will have implications for other infectious diseases, autoimmunity, clinical study design, and immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.204.Supp.225.1
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-03-17)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-03-17)
    Abstract: Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT]  〈  10), low (GMT = 28.3), or high (GMT  〉  761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus. Ferrets were then challenged with the wild-type virus and disease severity and immunologic parameters were studied. The severity of infection and symptom profile were inversely associated with pre-challenge HAI titers in a dose-dependent manner. A vaccinated ferret with no detectable HAI-antibodies but high flu-specific IgG-antibody titers mounted rapid functional antibodies after infection and experienced milder disease compared to other ferrets in the group. Compared to naïve ferrets, all vaccinated ferrets showed improved cellular immunity in the lungs and peripheral blood. High number of IFNγ + CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep44727
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 3
    Online Resource
    Online Resource
    H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines
    Springer Science and Business Media LLC ; 2017
    In:  npj Vaccines Vol. 2, No. 1 ( 2017-06-08)
    Details
    In: npj Vaccines, Springer Science and Business Media LLC, Vol. 2, No. 1 ( 2017-06-08)
    Abstract: Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine.
    Type of Medium: Online Resource
    ISSN: 2059-0105
    URL: Article
    DOI: 10.1038/s41541-017-0017-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2882262-6
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  • 4
    Online Resource
    Online Resource
    Impact of Adjuvants on the Immunogenicity and Efficacy of Split-Virion H7N9 Vaccine in Ferrets
    Oxford University Press (OUP) ; 2015
    In:  Journal of Infectious Diseases Vol. 212, No. 4 ( 2015-08-15), p. 542-551
    Details
    In: Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 212, No. 4 ( 2015-08-15), p. 542-551
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiv099
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 1473843-0
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  • 5
    Online Resource
    Online Resource
    Herpesvirus co-infection alters immune responses to human influenza virus infection.
    The American Association of Immunologists ; 2018
    In:  The Journal of Immunology Vol. 200, No. 1_Supplement ( 2018-05-01), p. 166.3-166.3
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 166.3-166.3
    Abstract: Herpesviruses (HVs) cause lifelong infections, and the majority of humans are infected with at least one; whether co-infection with HVs is beneficial or detrimental to the host is a current debate. We sought to determine if co-infection with HVs alters the magnitude or quality of the immune response to influenza infection, and, if so, the extent to which each virus affects illness outcome. We used a longitudinal study of naturally acquired influenza virus infection and linear regression modeling to determine differences in influenza viral load and shedding, cytokine levels, and severity scores, while taking into account the effects of confounding variables. Our results show co-infection with HVs does not significantly affect influenza virus kinetics or clearance, but Cytomegalovirus is associated with decreased symptom severity and increased antibody titers. Furthermore, co-infection alters cytokine levels involved in each step of the immune response. Changes in plasma and nasal wash cytokines were predominately associated with Herpes simplex virus 1/2 and Epstein-Barr virus co-infection, respectively. The cytokines most affected by HV serostatus in the plasma and nasal wash are MIP1b (adj. R2 = 0.3073) and RANTES (adj. R2 = 0.3604), respectively. The strongest effects on cytokine levels are associated with HV interactions and are primarily found in the plasma. In the nasal wash, co-infection mostly results in decreased levels of cytokines, including those implicated in immunopathology during influenza infection (e.g. IL1, MIP1, TNF-α, IL6). Understanding host-virus interactions during co-infection and how that relationship impacts disease severity can ultimately be used for better prognosis and/or prophylactic measures.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.200.Supp.166.3
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2018
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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