title: Cross-protective immunity against multiple influenza virus subtypes by a novel modified vaccinia Ankara (MVA) vectored vaccine in mice.
abstract: Development of an influenza vaccine that provides cross-protective immunity remains a challenge. Candidate vaccines based on a recombinant modified vaccinia Ankara (MVA) viral vector expressing antigens from influenza (MVA/Flu) viruses were constructed. A vaccine candidate, designated MVA/HA1/C13L/NP, that expresses the hemagglutinin from pandemic H1N1 (A/California/04/09) and the nucleoprotein (NP) from highly pathogenic H5N1 (A/Vietnam/1203/04) fused to a secretory signal sequence from vaccinia virus was highly protective. The vaccine elicited strong antibody titers to homologous H1N1 viruses while cross-reactive antibodies to heterologous viruses were not detectable. In mice, this MVA/HA1/C13L/NP vaccine conferred complete protection against lethal challenge with A/Vietnam/1203/04 (H5N1), A/Norway/3487-2/09 (pandemic H1N1) or A/Influenza/Puerto Rico/8/34 (seasonal H1N1) and partial protection (57.1%) against challenge with seasonal H3N2 virus (A/Aichi/68). The protective efficacy of the vaccine was not affected by pre-existing immunity to vaccinia. Our findings highlight MVA as suitable vector to express multiple influenza antigens that could afford broad cross-protective immunity against multiple subtypes of influenza virus.
authors: Inviragen, Inc., 6502 Odana Rd, Madison, WI 53719, USA. jbrewoo@inviragen.com
authors: Joseph N
authors: JN
authors: Brewoo
authors: Tim D
authors: TD
authors: Powell
authors: Jeremy C
authors: JC
authors: Jones
authors: Nancy A
authors: NA
authors: Gundlach
authors: Ginger R
authors: GR
authors: Young
authors: Haiyan
authors: H
authors: Chu
authors: Subash C
authors: SC
authors: Das
authors: Charalambos D
authors: CD
authors: Partidos
authors: Dan T
authors: DT
authors: Stinchcomb
authors: Jorge E
authors: JE
authors: Osorio
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D005822:Genetic Vectors; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D006388:Hemagglutinins; D007252:Influenza Vaccines
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