Abstract
Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a strong neutralizing antibody response against influenza virus. A complete protection was conferred to the immunized mice when challenged with a lethal dose of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as inert antigen in mice, since naturally inactivated over 20°C, mice immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also completely protected from a lethal challenge. Novirhabdoviruses platform are of particular interest as vaccines for mammals since they are cost effective to produce, relatively easy to generate and very effective to protect immunized animals.
Highlights
Regarding vaccination strategies against virus, vaccine approaches can be divided into two large groups: (i) Live vaccines, mainly consisting of live attenuated viruses and replicating recombinant virus vectors, and (ii) killed or subunit vaccines such as inactivated viruses, viruslike particles (VLP), DNA vaccines, recombinant proteins or subunit particles
Novirhabdovirus platforms offer numerous advantages: 1) they are easy and fast to construct, 2) they grow to high titer in fish cell lines, 3) they can incorporate a large panel of foreign antigens at their surface by adding the signal peptide and the transmembrane domain derived from the novirhabdovirus glycoprotein to the antigen of interest 4) they are self-adjuvanted and 5) they are naturally inactivated over 20°C and safe to use in mammals [11, 12]
The expression cassettes contain successively the signal peptide (SP) sequence derived from the Infectious Hematopoietic Necrosis Virus (IHNV) glycoprotein G gene, the coding sequence for the ectodomain and stalk from the influenza H1N1 A/PR/8/34 hemagglutinin (HA) and the transmembrane sequence (TM) from either IHNV or Viral Hemorrhagic Septicemia Virus (VHSV) G gene
Summary
Regarding vaccination strategies against virus, vaccine approaches can be divided into two large groups: (i) Live vaccines, mainly consisting of live attenuated viruses and replicating recombinant virus vectors, and (ii) killed or subunit vaccines such as inactivated viruses, viruslike particles (VLP), DNA vaccines, recombinant proteins or subunit particles. Efficient vaccine strategies do exist to prevent influenza infections; the segmented nature of the viral genome allowing potential reassortment with highly pathogenic strains and its ability to antigenically drift, confer to influenza virus the potential to rapidly emerge as new epidemic or pandemic strain, requiring the development of new vaccines. To thwart this and in order to provide an effective protection to populations, more effective influenza vaccines, greater production capacity, and faster throughput will be required [9]. We aimed to evaluate the potential of the novirhabdovirus platforms as recombinant vaccines against influenza infection in a mouse model
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
