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Published on: December 1, 2017
A protective measles virus-derived vaccine inducing long-lasting immune responses against influenza A virus H7N9
Cindy Hörner1,2, Anna H Fiedler1,2, Bianca S Bodmer1,3
1Section 4/3: Product Testing of IVMPs, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.
Abstract:
A novel Influenza A virus (subtype H7N9) emerged in spring 2013 and caused considerable mortality in zoonotically infected patients. To be prepared for potential pandemics, broadly effective and safe vaccines are crucial. Recombinant measles virus (MeV) encoding antigens of foreign pathogens constitutes a promising vector platform to generate novel vaccines. To characterize the efficacy of H7N9 antigens in a prototypic vaccine platform technology, we generated MeVs encoding either neuraminidase (N9) or hemagglutinin (H7). Moraten vaccine strain-derived vaccine candidates were rescued; they replicated with efficiency comparable to that of the measles vaccine, robustly expressed H7 and N9, and were genetically stable over 10 passages. Immunization of MeV-susceptible mice triggered the production of antibodies against H7 and N9, including hemagglutination-inhibiting and neutralizing antibodies induced by MVvac2-H7(P) and neuraminidase-inhibiting antibodies by MVvac2-N9(P). Vaccinated mice also developed long-lasting H7- and N9-specific T cells. Both MVvac2-H7(P) and MVvac2-N9(P)-vaccinated mice were protected from lethal H7N9 challenge.
Insights
This study demonstrates that a novel vaccine using a measles virus (MeV) vector effectively protects mice against lethal H7N9 influenza. The recombinant MeV vaccines expressing H7 or N9 antigens induced robust immune responses and long-lasting protection.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Novel Influenza A virus (H7N9) emerged in 2013, causing significant mortality.
- Broadly effective and safe vaccines are critical for pandemic preparedness.
- Recombinant measles virus (MeV) is a promising vaccine vector platform.
Purpose of the Study:
- To evaluate the efficacy of H7N9 antigens within a recombinant MeV vaccine platform.
- To characterize the immunogenicity and protective capabilities of these novel vaccine candidates.
Main Methods:
- Generated recombinant MeV vectors encoding H7 (hemagglutinin) or N9 (neuraminidase) antigens.
- Assessed vaccine replication, expression, and genetic stability in vitro.
- Immunized mice with MeV-H7 or MeV-N9 vaccine candidates.
- Evaluated antibody and T cell responses, and protection against lethal H7N9 challenge.
Main Results:
- Recombinant MeV vaccines (MVvac2-H7(P) and MVvac2-N9(P)) expressed H7 and N9 robustly and were genetically stable.
- Immunization induced H7- and N9-specific antibodies, including hemagglutination-inhibiting, neutralizing, and neuraminidase-inhibiting antibodies.
- Vaccinated mice developed long-lasting H7- and N9-specific T cell responses.
- Both vaccine candidates conferred complete protection against lethal H7N9 challenge.
Conclusions:
- Recombinant MeV vectors are effective platforms for delivering H7N9 antigens.
- These vaccines elicit protective immune responses against H7N9 influenza.
- This platform holds promise for developing broadly effective pandemic vaccines.
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