title: Genetic Adjuvantation of Recombinant MVA with CD40L Potentiates CD8 T Cell Mediated Immunity.
abstract: Modified vaccinia Ankara (MVA) is a safe and promising viral vaccine vector that is currently investigated in several clinical and pre-clinical trials. In contrast to inactivated or sub-unit vaccines, MVA is able to induce strong humoral as well as cellular immune responses. In order to further improve its CD8 T cell inducing capacity, we genetically adjuvanted MVA with the coding sequence of murine CD40L, a member of the tumor necrosis factor superfamily. Immunization of mice with this new vector led to strongly enhanced primary and memory CD8 T cell responses. Concordant with the enhanced CD8 T cell response, we could detect stronger activation of dendritic cells and higher systemic levels of innate cytokines (including IL-12p70) early after immunization. Interestingly, acquisition of memory characteristics (i.e., IL-7R expression) was accelerated after immunization with MVA-CD40L in comparison to non-adjuvanted MVA. Furthermore, the generated cytotoxic T-lymphocytes (CTLs) also showed improved functionality as demonstrated by intracellular cytokine staining and in vivo killing activity. Importantly, the superior CTL response after a single MVA-CD40L immunization was able to protect B cell deficient mice against a fatal infection with ectromelia virus. Taken together, we show that genetic adjuvantation of MVA can change strength, quality, and functionality of innate and adaptive immune responses. These data should facilitate a rational vaccine design with a focus on rapid induction of large numbers of CD8 T cells able to protect against specific diseases.
authors.affiliation: Department of Research Immunology, Bavarian Nordic GmbH , Martinsried , Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Lauterbach
authors.forename: Juliane
authors.initials: J
authors.lastname: Pätzold
authors.forename: Ronny
authors.initials: R
authors.lastname: Kassub
authors.forename: Barbara
authors.initials: B
authors.lastname: Bathke
authors.forename: Kay
authors.initials: K
authors.lastname: Brinkmann
authors.forename: Paul
authors.initials: P
authors.lastname: Chaplin
authors.forename: Mark
authors.initials: M
authors.lastname: Suter
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hochrein
keywords: CD40L; CD8 T cells; T cell memory; co-stimulation; ectromelia virus; modified vaccinia Ankara; vaccination; viral vaccines