Evaluation of Murine Immune Responses to Improved Bivalent Vaccines against Rabies Virus and Ebola Viruses

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAID	VIROL-8

Authors

• A.B. Papaneri
• M. Willet
• C. Wirblich
• R.F. Johnson
• M.J. Schnell
• P.B. Jahrling

Abstract

Our recombinant rabies (RABV) vectored vaccine system is a reverse genetics system based on the SAD B19 RABV wildlife vaccine, which incorporates an ArgGlu change at amino acid 333 of RABV glycoprotein (G) that has been shown to greatly attenuate neurovirulence of RABV vaccine vectors in mice. This recombinant RABV vector (BNSP333) serves as a backbone for incorporation of foreign antigens from agents of interest to develop safe and effective bivalent vaccines. Recently, BNSP333 expressing the ebolavirus (EBOV) Zaire glycoprotein (ZGP) was proven efficacious in nonhuman primates. For developing a multivalent RABV and filovirus vaccine, we have constructed BNSP333-SGP, which expresses Sudan ebolavirus (SUDV) GP. We have also improved BNSP333-ZGP and BNSP333-SGP via codon-optimization, which increased GP incorporation on the virion surface. As expected, our results confirmed that all constructs are apathogenic and non-neuroinvasive in adult mice. We also analyzed the humoral immune response against SUDV GP, EBOV GP and RABV G and determined if the induced antibodies differ in isotype. Results indicate a robust multivalent antibody response, which is Th1-biased and likely not cross-protective for EBOV and SUDV. These data indicate that a multivalent vaccine against RABV and filoviruses is achievable, bolstering the marketability of this urgently needed vaccine.

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