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Enhancing the Efficacy of Adenovirus-5 Vectored Ebola Virus Vaccines

Ebola Monoclonal Antibody CountermeasuresThe U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Virology Division, Pathogenesis and Immunology Branch has been tasked by the Defense Threat Reduction Agency to investigate a potential for enhanced efficacy adenovirus-5 vectored Ebola Virus (EBOV) vaccines.

One vaccine will express the glycoprotein (GP) of Ebola Virus (EBOV) and the other will express a multimerized CD40 Ligand (CD40L)/EBOV GP antigen.

CD40L functions in a role that provides crucial information between cell types to generate productive immune responses.  The cognate receptor for CD40L and CD40 is expressed by antigen-presenting cells.

CD40L, therefore, can be utilized to direct an antigen of interest to a specific cell type (i.e. antigen-presenting cells).  As antigen-presenting cells are pivotal initiators of immune responses, targeting an antigen of interest specifically to them – by virtue of CD40L – presents a means of efficient antigen delivery that can elicit robust immune responses.

Furthermore, the biology behind CD40L and CD40 interactions results in a phenomenon known as cross-presentation, which increases the breadth of T cell responses that can be derived from vaccination. Multimerized formulations of CD40L-EBOV GP are essential as CD40 expression on antigen-presenting cells is best engaged by multiple CD40L molecules.

Current Ebola EBOV vaccines utilize the GP of EBOV to elicit immune responses.  The goal is to evaluate the relative potency of EBOV GP vaccination in an Adenovirus-5 (Ad5) vector compared to an identically vectored EBOV GP that utilizes CD40L targeting.

A contractor is sought to provide USAMRIID with two batches of vaccine in an Ad5 vector.  One shall express EBOV GP and the other shall express a multimerized construct of CD40L/EBOV GP.  Each batch will need to be sufficient to vaccinate 300 mice at a dose of 1×108 infectious units (IU) per mouse.

The anticipated period of performance of the contract is a base year with four option years, beginning in July 2017.

Solicitation Number: W81XWH17T0117. The response deadline is Jun 05, 2017 10:00 am Eastern.


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