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Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin.
PLoS One. 2011 Mar 28; 6(3):e18314.Plos

Abstract

Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 10(7) virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses.

Authors+Show Affiliations

Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America. weaver.eric@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21464940

Citation

Weaver, Eric A., et al. "Protection Against Divergent Influenza H1N1 Virus By a Centralized Influenza Hemagglutinin." PloS One, vol. 6, no. 3, 2011, pp. e18314.
Weaver EA, Rubrum AM, Webby RJ, et al. Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin. PLoS One. 2011;6(3):e18314.
Weaver, E. A., Rubrum, A. M., Webby, R. J., & Barry, M. A. (2011). Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin. PloS One, 6(3), e18314. https://doi.org/10.1371/journal.pone.0018314
Weaver EA, et al. Protection Against Divergent Influenza H1N1 Virus By a Centralized Influenza Hemagglutinin. PLoS One. 2011 Mar 28;6(3):e18314. PubMed PMID: 21464940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin. AU - Weaver,Eric A, AU - Rubrum,Adam M, AU - Webby,Richard J, AU - Barry,Michael A, Y1 - 2011/03/28/ PY - 2010/12/29/received PY - 2011/02/24/accepted PY - 2011/4/6/entrez PY - 2011/4/6/pubmed PY - 2011/7/19/medline SP - e18314 EP - e18314 JF - PloS one JO - PLoS One VL - 6 IS - 3 N2 - Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 10(7) virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21464940/Protection_against_divergent_influenza_H1N1_virus_by_a_centralized_influenza_hemagglutinin_ L2 - https://dx.plos.org/10.1371/journal.pone.0018314 DB - PRIME DP - Unbound Medicine ER -