T and B cell memory responses in 2012 filovirus outbreak survivors

From 2011 to the present, there have been four confirmed filovirus outbreaks with a fifth case involving a single patient. Four outbreaks/cases were attributed to the Ebolavirus genus, with Marburgvirus responsible for one. With the high lethality rates seen in these outbreaks (generally ~40-90%), and the potentially dramatic disease sequelae, filovirus outbreaks can devastate local communities and present great health risks for affected regions. These issues obviate the need for effective vaccines and therapeutics to limit and manage future outbreaks. In 2012 alone, three outbreaks occurred in Uganda - two of Sudan virus and one Marburg virus. We collected PBMC and serum samples from survivors from each outbreak to evaluate the presence of immune memory and its composition. Serum antibodies displayed broad specificity to Marburg virus and Sudan virus glycoprotein in addition to other proteins. Virtually all serum samples displayed neutralizing activity. PBMCs stimulated with viral and recombinant antigen were evaluated by flow cytometry for functional parameters as well as level of antigen-responsive T cells. Cytokines in the supernatants of these cultures were determined by multiplex ELISA. Cytokine responses were largely pro-inflammatory produced predominantly by CD4 T cells. Establishing immune memory parameters and the nature thereof gives us targets for vaccine development and opens avenues for development of immune-based therapeutics.