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2023 FDA Science Forum

Evaluation of the role of Type I IFN response in the protective immunity induced by live attenuated Leishmania parasite vaccines

Download the Poster (PDF; 0.83 MB)
Authors:
Poster Author(s)
Sepahpour, Telly, FDA/CBER/OBRR; Ismail, Nevien, FDA/CBER/OBRR; Alshaweesh, Jalal, Nagasaki University, Japan; Hamano, Shinjiro, Nagasaki University, Japan; Gannavaram, Sreenivas, FDA/CBER/OBRR; Dey, Ranadhir, FDA/CBER/OBRR; Nakhasi, Hira, FDA/CBER/OBRR.
Center:
Contributing Office
Center for Biologics Evaluation and Research

Abstract

Poster Abstract

Background:

Leishmaniasis is a vector borne disease caused by the various strains of Leishmania parasites and is endemic across the world including the United States. The disease is transmitted to humans through the bite of infected sandfly and blood transfusions. Currently, there are no FDA-approved anti-leishmania vaccines or donor screening assays, while treatment options are limited.

Purpose:

We aim to elucidate the role of type I IFN response in protection following immunization with live attenuated leishmania parasites. Previous studies in parasitic and viral pathogenesis established that type I interferons (IFNs) adversely impact adaptive immunity.

Methods:

RNA isolated from the inoculation site in C57Bl/6 mice and Human PBMCs (n=4) following infection with wildtype LmWT or LmCen-/- was analyzed by the NanoString Platform 4.0 to identify Differentially Expressed Genes. Flow Cytometry analysis was conducted on cells isolated from lymph node and spleens of C57Bl/6 mice that were immunized with LmCen-/- and challenged with virulent L. donovani. Cytokines (IFN-alpha/beta, IL-2, IL-4, IFN-gamma, IL-10) from these cells were detected via ELISA.

Results:

Our results show that immunization with LmCen-/- induces signature transcriptomic patterns that differentiates it from the wildtype infection. The induction of a protective Th1 response as indicated by a strong IFN-gamma, IL-2 and TNF production and a reduced IL-10 was coincident with a decline in the type-I IFN response as measured by IFN-alpha/IFN-beta in the LmCen-/- immunized mice indicating that type-I IFN and Th1 responses are negatively correlated.

Conclusion:

Application of transcriptomic analysis to LmCen-/- vaccine candidate identified signature transcriptomic patterns between the immunization and the infection environments specifically IRF-7 and IRF-3 that regulate type-I IFN responses. The adaptive immune response to immunization showed an upregulation of IL-2, TNF and INF-gamma, hallmarks of a Th1 response with a concomitant reduction in the type-I IFN response suggesting that downregulation of type-I IFN response is critical to inducing protective immunity.

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2023 Science Forum Poster Thumbnail – Evaluation of the role of Type I IFN response in the protective immunity induced by live attenuated Leishmania parasite vaccines

Download the Poster (PDF; 0.83 MB)

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