PMID- 24523886
OWN - NLM
STAT- MEDLINE
DCOM- 20141028
LR  - 20220602
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - MVA vectors expressing conserved influenza proteins protect mice against lethal 
      challenge with H5N1, H9N2 and H7N1 viruses.
PG  - e88340
LID - 10.1371/journal.pone.0088340 [doi]
LID - e88340
AB  - BACKGROUND: The availability of a universal influenza vaccine able to induce 
      broad cross-reactive immune responses against diverse influenza viruses would 
      provide an alternative to currently available strain-specific vaccines. We 
      evaluated the ability of vectors based on modified vaccinia virus Ankara (MVA) 
      expressing conserved influenza proteins to protect mice against lethal challenge 
      with multiple influenza subtypes. METHODS: Mice were immunized with MVA vectors 
      expressing H5N1-derived nucleoprotein (NP), the stem region of hemagglutinin 
      (HA), matrix proteins 1 and 2 (M1 and M2), the viral polymerase basic protein 1 
      (PB1), or the HA stem fused to a quadrivalent matrix protein 2 extracellular 
      domain (M2e). Immunized mice were challenged with lethal doses of H5N1, H7N1 or 
      H9N2 virus and monitored for disease symptoms and weight loss. To investigate the 
      influence of previous exposure to influenza virus on protective immune responses 
      induced by conserved influenza proteins, mice were infected with pandemic H1N1 
      virus (H1N1pdm09) prior to immunization and subsequently challenged with H5N1 
      virus. Antibody and T cell responses were assessed by ELISA and flow cytometry, 
      respectively. RESULTS: MVA vectors expressing NP alone, or co-expressed with 
      other conserved influenza proteins, protected mice against lethal challenge with 
      H5N1, H7N1 or H9N2 virus. Pre-exposure to H1N1pdm09 increased protective efficacy 
      against lethal H5N1 challenge. None of the other conserved influenza proteins 
      provided significant levels of protection against lethal challenge. NP-expressing 
      vectors induced high numbers of influenza-specific CD4(+) and CD8(+) T cells and 
      high titer influenza-specific antibody responses. Higher influenza-specific 
      CD4(+) T cell responses and NP-specific CD8(+) T cell responses were associated 
      with increased protective efficacy. CONCLUSIONS: MVA vectors expressing influenza 
      NP protect mice against lethal challenge with H5N1, H7N1 and H9N2 viruses by a 
      mechanism involving influenza-specific CD4(+) and CD8(+) T cell responses.
FAU - Hessel, Annett
AU  - Hessel A
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Savidis-Dacho, Helga
AU  - Savidis-Dacho H
AD  - Pharmacology, Baxter Bioscience, Orth/Donau, Austria.
FAU - Coulibaly, Sogue
AU  - Coulibaly S
AD  - Pharmacology, Baxter Bioscience, Orth/Donau, Austria.
FAU - Portsmouth, Daniel
AU  - Portsmouth D
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Kreil, Thomas R
AU  - Kreil TR
AD  - Global Pathogen Safety, Baxter Bioscience, Vienna, Austria.
FAU - Crowe, Brian A
AU  - Crowe BA
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Schwendinger, Michael G
AU  - Schwendinger MG
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Pilz, Andreas
AU  - Pilz A
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Barrett, P Noel
AU  - Barrett PN
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Falkner, Falko G
AU  - Falkner FG
AD  - Biologicals R&D, Baxter Bioscience, Orth/Donau, Austria.
FAU - Schafer, Birgit
AU  - Schafer B
AD  - Vaccine R&D, Baxter Bioscience, Orth/Donau, Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140211
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Influenza Vaccines)
SB  - IM
MH  - Animals
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Influenza A Virus, H5N1 Subtype/*immunology
MH  - Influenza A Virus, H7N1 Subtype/*immunology
MH  - Influenza A Virus, H9N2 Subtype/*immunology
MH  - Influenza Vaccines/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Orthomyxoviridae Infections/*prevention & control/virology
MH  - T-Lymphocytes/immunology
MH  - Vaccinia virus/*immunology
PMC - PMC3921149
COIS- Competing Interests: AH, BS, HS-D, SC, DP, TRK, BAC, MGS, AP, PNB and FGF report 
      being employed by Baxter. HS-D, SC, TRK, BAC, MGS, PNB and FGF report having an 
      equity interest in the company. AH, BS, TRK, PNB and FGF report a submitted 
      patent on MVA vectors: "Recombinant viral vectors and methods for inducing a 
      heterosubtypic immune response to influenza A virses" WO 2012/106231; 
      PCT/US2012/023085. This does not alter the authors' adherence to all the PLOS ONE 
      policies on sharing data and materials.
EDAT- 2014/02/14 06:00
MHDA- 2014/10/29 06:00
PMCR- 2014/02/11
CRDT- 2014/02/14 06:00
PHST- 2013/09/06 00:00 [received]
PHST- 2014/01/12 00:00 [accepted]
PHST- 2014/02/14 06:00 [entrez]
PHST- 2014/02/14 06:00 [pubmed]
PHST- 2014/10/29 06:00 [medline]
PHST- 2014/02/11 00:00 [pmc-release]
AID - PONE-D-13-36718 [pii]
AID - 10.1371/journal.pone.0088340 [doi]
PST - epublish
SO  - PLoS One. 2014 Feb 11;9(2):e88340. doi: 10.1371/journal.pone.0088340. eCollection 
      2014.