Polyfunctional CD4 T cell responses to a set of pathogenic arenaviruses provide broad population coverageReport as inadecuate




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Immunome Research

, 6:4

First Online: 17 May 2010Received: 09 February 2010Accepted: 17 May 2010

Abstract

BackgroundSeveral arenaviruses cause severe hemorrhagic fever and aseptic meningitis in humans for which no licensed vaccines are available. A major obstacle for vaccine development is pathogen heterogeneity within the Arenaviridae family. Evidence in animal models and humans indicate that T cell and antibody-mediated immunity play important roles in controlling arenavirus infection and replication. Because CD4 T cells are needed for optimal CD8 T cell responses and to provide cognate help for B cells, knowledge of epitopes recognized by CD4 T cells is critical to the development of an effective vaccine strategy against arenaviruses. Thus, the goal of the present study was to define and characterize CD4 T cell responses from a broad repertoire of pathogenic arenaviruses including lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses and to provide determinants with the potential to be incorporated into a multivalent vaccine strategy.

ResultsBy inoculating HLA-DRB1*0101 transgenic mice with a panel of recombinant vaccinia viruses, each expressing a single arenavirus antigen, we identified 37 human HLA-DRB1*0101-restricted CD4 T cell epitopes from the 7 antigenically distinct arenaviruses. We showed that the arenavirus-specific CD4 T cell epitopes are capable of eliciting T cells with a propensity to provide help and protection through CD40L and polyfunctional cytokine expression. Importantly, we demonstrated that the set of identified CD4 T cell epitopes provides broad, non-ethnically biased population coverage of all 7 arenavirus species targeted by our studies.

ConclusionsThe identification of CD4 T cell epitopes, with promiscuous binding properties, derived from 7 different arenavirus species will aid in the development of a T cell-based vaccine strategy with the potential to target a broad range of ethnicities within the general population and to protect against both Old and New World arenavirus infection.

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Author: Maya F Kotturi - Jason Botten - Matt Maybeno - John Sidney - Jean Glenn - Huynh-Hoa Bui - Carla Oseroff - Shane Crotty -

Source: https://link.springer.com/



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