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  • 1
    Online Resource
    Online Resource
    Distinct TLR adjuvants differentially stimulate systemic and local innate immune responses in nonhuman primates
    American Society of Hematology ; 2012
    In:  Blood Vol. 119, No. 9 ( 2012-03-01), p. 2044-2055
    Details
    In: Blood, American Society of Hematology, Vol. 119, No. 9 ( 2012-03-01), p. 2044-2055
    Abstract: TLR ligands (TLR-Ls) represent novel vaccine adjuvants, but their immunologic effects in humans remain poorly defined in vivo. In the present study, we analyzed the innate responses stimulated by different TLR-Ls in rhesus macaques. MPL (TLR4-L), R-848 (TLR7/8-L), or cytosine-phosphate-guanine oligodeoxynucleotide (TLR9-L) induced a rapid and robust expansion of blood neutrophils, with a concomitant reduction in PBMCs. Furthermore, all TLR-Ls induced rapid (3-8 hours) expansion of CD14+ monocytes, but only TLR7/8-L and TLR9-L mobilized the CD14+CD16+ and CD14dimCD16++ monocytes, and only TLR7/8-L and TLR9-L induced activation of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs), production of IP-10 and type-I IFN, and expression of type-I IFN–related and chemokine genes in the blood. In the draining lymph nodes (LNs), consistent with the effects in blood, all TLR-Ls induced expansion of CD14+ monocytes, but only TLR7/8-L and TLR9-L expanded the activated CD14+CD16+ cells. TLR4-L and TLR9-L differentially induced the expansion of mDCs and pDCs (1-3 days), but did not activate DCs. In contrast, TLR7/8-L did not induce DC expansion, but did activate mDCs. Finally, both TLR9-L and TLR7/8-L induced the expression of genes related to chemokines and type-I IFNs in LNs. Thus different TLR-Ls mediate distinct signatures of early innate responses both locally and systemically.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2011-10-388579
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 2
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    Vaccine Activation of the Nutrient Sensor GCN2 in Dendritic Cells Enhances Antigen Presentation
    American Association for the Advancement of Science (AAAS) ; 2014
    In:  Science Vol. 343, No. 6168 ( 2014-01-17), p. 313-317
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 343, No. 6168 ( 2014-01-17), p. 313-317
    Abstract: The yellow fever vaccine YF-17D is one of the most successful vaccines ever developed in humans. Despite its efficacy and widespread use in more than 600 million people, the mechanisms by which it stimulates protective immunity remain poorly understood. Recent studies using systems biology approaches in humans have revealed that YF-17D–induced early expression of general control nonderepressible 2 kinase (GCN2) in the blood strongly correlates with the magnitude of the later CD8 + T cell response. We demonstrate a key role for virus-induced GCN2 activation in programming dendritic cells to initiate autophagy and enhanced antigen presentation to both CD4 + and CD8 + T cells. These results reveal an unappreciated link between virus-induced integrated stress response in dendritic cells and the adaptive immune response.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1246829
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2014
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    SSG: 11
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  • 3
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    Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 7 ( 2016-02-16), p. 1853-1858
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 7 ( 2016-02-16), p. 1853-1858
    Abstract: The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4 + T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1519690113
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
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    SSG: 11
    SSG: 12
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  • 4
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    Systems vaccinology : its promise and challenge for HIV vaccine development
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Current Opinion in HIV and AIDS Vol. 7, No. 1 ( 2012-01), p. 24-31
    Details
    In: Current Opinion in HIV and AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 1 ( 2012-01), p. 24-31
    Type of Medium: Online Resource
    ISSN: 1746-630X
    URL: Article
    DOI: 10.1097/COH.0b013e32834dc37b
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 5
    Online Resource
    Online Resource
    Machine Learning for Predicting Vaccine Immunogenicity
    Institute for Operations Research and the Management Sciences (INFORMS) ; 2016
    In:  Interfaces Vol. 46, No. 5 ( 2016-10), p. 368-390
    Details
    In: Interfaces, Institute for Operations Research and the Management Sciences (INFORMS), Vol. 46, No. 5 ( 2016-10), p. 368-390
    Abstract: The ability to predict how different individuals will respond to vaccination and to understand what best protects individuals from infection greatly facilitates developing next-generation vaccines. It facilitates both the rapid design and evaluation of new and emerging vaccines and identifies individuals unlikely to be protected by vaccine. We describe a general-purpose machine-learning framework, DAMIP, for discovering gene signatures that can predict vaccine immunity and efficacy. DAMIP is a multiple-group, concurrent classifier that offers unique features not present in other models: a nonlinear data transformation to manage the curse of dimensionality and noise; a reserved-judgment region that handles fuzzy entities; and constraints on the allowed percentage of misclassifications. Using DAMIP, implemented results for yellow fever demonstrated that, for the first time, a vaccine’s ability to immunize a patient could be successfully predicted (with accuracy of greater than 90 percent) within one week after vaccination. A gene identified by DAMIP, EIF2AK4, decrypted a seven-decade-old mystery of vaccination. Results for flu vaccine demonstrated DAMIP’s applicability to both live-attenuated and inactivated vaccines. Results in a malaria study enabled targeted delivery to individual patients. Our project’s methods and findings permit highlighting and probabilistically prioritizing hypothesis design to enhance biological discovery. Moreover, they guide the rapid development of better vaccines to fight emerging infections, and improve monitoring for poor responses in the elderly, infants, or others with weakened immune systems. In addition, the project’s work should help with universal flu-vaccine design.
    Type of Medium: Online Resource
    ISSN: 0092-2102 , 1526-551X
    URL: Article
    DOI: 10.1287/inte.2016.0862
    Language: English
    Publisher: Institute for Operations Research and the Management Sciences (INFORMS)
    Publication Date: 2016
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    SSG: 24,1
    SSG: 3,2
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  • 6
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    Immunity to viruses: learning from successful human vaccines
    Wiley ; 2013
    In:  Immunological Reviews Vol. 255, No. 1 ( 2013-09), p. 243-255
    Details
    In: Immunological Reviews, Wiley, Vol. 255, No. 1 ( 2013-09), p. 243-255
    Abstract: For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using ‘model antigens’, such as chicken egg ovalbumin or nitrophenyl haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights about the mechanisms of immune regulation, but their relevance to humans has been questioned. In another universe, vaccinologists have relied on human clinical trials to assess vaccine efficacy, but have done little to take advantage of such trials for studying the nature of immune responses to vaccination. The human model provides a nexus between these two universes, and recent studies have begun to use this model to study the molecular profile of innate and adaptive responses to vaccination. Such ‘systems vaccinology’ studies are beginning to provide mechanistic insights about innate and adaptive immunity in humans. Here, we present an overview of such studies, with particular examples from studies with the yellow fever and the seasonal influenza vaccines. Vaccination with the yellow fever vaccine causes a systemic acute viral infection and thus provides an attractive model to study innate and adaptive responses to a primary viral challenge. Vaccination with the live attenuated influenza vaccine causes a localized acute viral infection in mucosal tissues and induces a recall response, since most vaccinees have had prior exposure to influenza, and thus provides a unique opportunity to study innate and antigen‐specific memory responses in mucosal tissues and in the blood. Vaccination with the inactivated influenza vaccine offers a model to study immune responses to an inactivated immunogen. Studies with these and other vaccines are beginning to reunite the estranged fields of immunology and vaccinology, yielding unexpected insights about mechanisms of viral immunity. Vaccines that have been proven to be of immense benefit in saving lives offer us a new fringe benefit: lessons in viral immunology.
    Type of Medium: Online Resource
    ISSN: 0105-2896 , 1600-065X
    URL: Issue
    URL: Article
    DOI: 10.1111/imr.2013.255.issue-1
    DOI: 10.1111/imr.12099
    Language: English
    Publisher: Wiley
    Publication Date: 2013
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    SSG: 12
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  • 7
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    Systems vaccinology: learning to compute the behavior of vaccine induced immunity
    Wiley ; 2012
    In:  WIREs Systems Biology and Medicine Vol. 4, No. 2 ( 2012-03), p. 193-205
    Details
    In: WIREs Systems Biology and Medicine, Wiley, Vol. 4, No. 2 ( 2012-03), p. 193-205
    Abstract: The goal of systems biology is to access and integrate information about the parts (e.g., genes, proteins, cells) of a biological system with a view to computing and predicting the behavior of the system. The past decade has witnessed technological revolutions in the capacity to make high throughput measurements about the behavior of genes, proteins, and cells. Such technologies are widely used in biological research and in medicine, such as toward prognosis and therapy response prediction in cancer patients. More recently, systems biology is being applied to vaccinology, with the goal of: (1) understanding the mechanisms by which vaccines stimulate protective immunity, and (2) predicting the immunogenicity or efficacy of vaccines. Here, we review the recent advances in this area, and highlight the biological and computational challenges posed. WIREs Syst Biol Med 2012, 4:193–205. doi: 10.1002/wsbm.163 This article is categorized under: Models of Systems Properties and Processes 〉 Cellular Models
    Type of Medium: Online Resource
    ISSN: 1939-5094 , 1939-005X
    URL: Issue
    URL: Article
    DOI: 10.1002/wsbm.v4.2
    DOI: 10.1002/wsbm.163
    Language: English
    Publisher: Wiley
    Publication Date: 2012
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  • 8
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    Gene profiling of Chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis
    Wiley ; 2012
    In:  Arthritis & Rheumatism Vol. 64, No. 11 ( 2012-11), p. 3553-3563
    Details
    In: Arthritis & Rheumatism, Wiley, Vol. 64, No. 11 ( 2012-11), p. 3553-3563
    Type of Medium: Online Resource
    ISSN: 0004-3591
    URL: Article
    DOI: 10.1002/art.34631
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2754614-7
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  • 9
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    Systems Vaccinology
    Elsevier BV ; 2010
    In:  Immunity Vol. 33, No. 4 ( 2010-10), p. 516-529
    Details
    In: Immunity, Elsevier BV, Vol. 33, No. 4 ( 2010-10), p. 516-529
    Type of Medium: Online Resource
    ISSN: 1074-7613
    URL: Article
    DOI: 10.1016/j.immuni.2010.10.006
    RVK:
    XA 48754.8
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 2001966-X
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  • 10
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    Systems vaccinology: Enabling rational vaccine design with systems biological approaches
    Elsevier BV ; 2015
    In:  Vaccine Vol. 33, No. 40 ( 2015-09), p. 5294-5301
    Details
    In: Vaccine, Elsevier BV, Vol. 33, No. 40 ( 2015-09), p. 5294-5301
    Type of Medium: Online Resource
    ISSN: 0264-410X
    URL: Article
    DOI: 10.1016/j.vaccine.2015.03.072
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 1468474-3
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