Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP as an Intranasal Ebola Vaccine

Ebola virus (EBOV) hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. EBOV is transmitted by contact with body fluids from infected individuals including droplets or aerosols. Aerosolized EBOV could also be exploited for intentional virus spread. Therefore, vaccines that protect against mucosal and systemic exposure are needed.

The NIH/NIAID has developed recombinant human parainfluenza virus type 1 (rHPIV1) bearing a stabilized attenuating mutation in the P/C gene to express the membrane-anchored form of EBOV glycoprotein GP as an intranasal (IN) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or a chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were substituted with those of the HPIV1 F protein in an effort to increase packaging into the vector particle and enhance immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1. All vectors replicated to high titers in vitro and had stable GP expression. Viruses were attenuated and replicated at low titers in the respiratory tract of African green monkeys. Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity. Overall, the candidate expressing full-length GP from the Pre-N position was the most immunogenic.

This invention relates to an attenuated and immunogenic IN vaccine candidate expected to be well tolerated in humans and is available for clinical evaluation.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404, as well as for further development and evaluation under a research collaboration.