Grant: Operating Grant: Innovative Biomedical and Clinical HIV/AIDS Research
Institut de recherches cliniques de Montréal
$248,700.00
Examining the role of plasmacytoid dendritic cells in the control of HIV infection using humanized mice
FY 2016-17
Summary
Increasing evidence suggests that the first immune responses, also termed innate immunity, are key determinants of the outcome of HIV infection. Modulation of innate immunity, thus has the potential to constitute a powerful effector strategy to complement traditional approaches to HIV prevention and therapy. However, a better understanding of the contribution of specific components of the host innate response to early HIV control is a critical prerequisite for the use of innate immunity in vaccine or therapy design. This proposal focuses on plasmacytoid Dendritic Cells (pDCs), a critical cellular component of our innate immune system that is activated early on during HIV infection and that is thought to mediate potent antiviral activities. However, these pDCs are quantitatively and functionally affected in HIV infection. CDX-301 is a form of a factor naturally produced by humans, which induces an expansion of immune cell precursors as well as of pDCs. CDX-301 is currently in clinical development for cancer immunotherapy and as a vaccine adjuvant. In this project, we will study the role of pDCs during early HIV infection by testing whether their expansion by CDX-301 can mediate potent immune responses that could contribute to HIV control. Towards this goal, we will use mouse that are transplanted with a human immune system. These so called humanized (hu) mice are susceptible to HIV infection and recapitulate most of the characteristics of HIV-induced disease. Specifically, we will analyze the effect of CDX-301-mediated pDC expansion on HIV infection and development of disease in hu mice. Furthermore, we will characterize the immune responses induced by CDX-301-mediated pDC expansion and their effects on HIV infection. Ultimately, understanding how CDX-301 and pDCs can mediate control of HIV infection following virus transmission will offer unique opportunities for the development of improved or novel preventive and therapeutic strategies against HIV infection
Department
Program
Operating Grant: Innovative Biomedical and Clinical HIV/AIDS Research
Location
Quebec, Canada
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
350795
Name
Cohen Eric A
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Infection and Immunity
Theme2
Biomedical
Prcname2
Innovative Biomedical and Clinical HIV/AIDS Research
Projecttitle
Examining the role of plasmacytoid dendritic cells in the control of HIV infection using humanized mice
Programtype2
Operating Grants
Orgnameinp2
Institut de recherches cliniques de Montréal
Cihramount2
$248,700
Cihrequipment2
$0
Programname2
Operating Grant: Innovative Biomedical and Clinical HIV/AIDS Research
Keyworddelim
Biology Of Early Hiv Infection; Dendritic Cells; Flow Cytometry; Flt3 Ligand; Hiv Replication And Spread; Hiv-1 Pathogenesis; Hiv/Aids; Humanized Mouse Models; Innate Immunity; Protective Immune Reponses
Abstract
Increasing evidence suggests that the first immune responses, also termed innate immunity, are key determinants of the outcome of HIV infection. Modulation of innate immunity, thus has the potential to constitute a powerful effector strategy to complement traditional approaches to HIV prevention and therapy. However, a better understanding of the contribution of specific components of the host innate response to early HIV control is a critical prerequisite for the use of innate immunity in vaccine or therapy design. This proposal focuses on plasmacytoid Dendritic Cells (pDCs), a critical cellular component of our innate immune system that is activated early on during HIV infection and that is thought to mediate potent antiviral activities. However, these pDCs are quantitatively and functionally affected in HIV infection. CDX-301 is a form of a factor naturally produced by humans, which induces an expansion of immune cell precursors as well as of pDCs. CDX-301 is currently in clinical development for cancer immunotherapy and as a vaccine adjuvant. In this project, we will study the role of pDCs during early HIV infection by testing whether their expansion by CDX-301 can mediate potent immune responses that could contribute to HIV control. Towards this goal, we will use mouse that are transplanted with a human immune system. These so called humanized (hu) mice are susceptible to HIV infection and recapitulate most of the characteristics of HIV-induced disease. Specifically, we will analyze the effect of CDX-301-mediated pDC expansion on HIV infection and development of disease in hu mice. Furthermore, we will characterize the immune responses induced by CDX-301-mediated pDC expansion and their effects on HIV infection. Ultimately, understanding how CDX-301 and pDCs can mediate control of HIV infection following virus transmission will offer unique opportunities for the development of improved or novel preventive and therapeutic strategies against HIV infection
Competitiondate
201606
Approvedterm2
1 yr 6 mths
Pinamesdelim
Cohen, Eric A; Haddad, Elie
Approvedterm
1 an 6 mois
Cihrcontribution2
~ $248,700~ $0~
