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A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets.
Vaccine. 2011 Apr 05; 29(16):3043-54.V

Abstract

Pandemic outbreaks of influenza are caused by the emergence of a pathogenic and transmissible virus to which the human population is immunologically naïve. Recent outbreaks of highly pathogenic avian influenza (HPAI) of the H5N1 subtype are of particular concern because of the high mortality rate (60% case fatality rate) and novel subtype. In order to develop a vaccine that elicits broadly reactive antibody responses against emerging H5N1 isolates, we utilized a novel antigen design technique termed computationally optimized broadly reactive antigen (COBRA). The COBRA HA sequence was based upon HA amino acid sequences from clade 2 H5N1 human infections and the expressed protein retained the ability to bind the receptor, as well as mediate particle fusion. Non-infectious recombinant VLP vaccines using the COBRA HA were purified from a mammalian expression system. Mice and ferrets vaccinated with COBRA HA H5N1 VLPs had protective levels of HAI antibodies to a representative isolates from each subclade of clade 2. Furthermore, VLP vaccinated animals were completely protected from a lethal challenge of the clade 2.2 H5N1 virus A/Whooper Swan/Mongolia/244/2005. This is the first report describing the use of COBRA-based antigen design. The COBRA HA H5N1 VLP vaccine elicited broadly reactive antibodies and is an effective influenza vaccine against HPAI virus.

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Authors+Show Affiliations

Giles BM
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Ross TM
No affiliation info available

MeSH

AnimalsAntibodies, ViralAntibody FormationAntigens, ViralComputational BiologyComputer-Aided DesignDogsDrug DesignFemaleFerretsHEK293 CellsHemagglutination Inhibition TestsHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H5N1 SubtypeInfluenza VaccinesMiceMice, Inbred BALB COrthomyxoviridae InfectionsTransfectionViral Plaque Assay

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21320540

Citation

Giles, Brendan M., and Ted M. Ross. "A Computationally Optimized Broadly Reactive Antigen (COBRA) Based H5N1 VLP Vaccine Elicits Broadly Reactive Antibodies in Mice and Ferrets." Vaccine, vol. 29, no. 16, 2011, pp. 3043-54.
Giles BM, Ross TM. A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine. 2011;29(16):3043-54.
Giles, B. M., & Ross, T. M. (2011). A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine, 29(16), 3043-54. https://doi.org/10.1016/j.vaccine.2011.01.100
Giles BM, Ross TM. A Computationally Optimized Broadly Reactive Antigen (COBRA) Based H5N1 VLP Vaccine Elicits Broadly Reactive Antibodies in Mice and Ferrets. Vaccine. 2011 Apr 5;29(16):3043-54. PubMed PMID: 21320540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. AU - Giles,Brendan M, AU - Ross,Ted M, Y1 - 2011/02/12/ PY - 2010/11/30/received PY - 2011/01/25/revised PY - 2011/01/29/accepted PY - 2011/2/16/entrez PY - 2011/2/16/pubmed PY - 2011/9/9/medline SP - 3043 EP - 54 JF - Vaccine JO - Vaccine VL - 29 IS - 16 N2 - Pandemic outbreaks of influenza are caused by the emergence of a pathogenic and transmissible virus to which the human population is immunologically naïve. Recent outbreaks of highly pathogenic avian influenza (HPAI) of the H5N1 subtype are of particular concern because of the high mortality rate (60% case fatality rate) and novel subtype. In order to develop a vaccine that elicits broadly reactive antibody responses against emerging H5N1 isolates, we utilized a novel antigen design technique termed computationally optimized broadly reactive antigen (COBRA). The COBRA HA sequence was based upon HA amino acid sequences from clade 2 H5N1 human infections and the expressed protein retained the ability to bind the receptor, as well as mediate particle fusion. Non-infectious recombinant VLP vaccines using the COBRA HA were purified from a mammalian expression system. Mice and ferrets vaccinated with COBRA HA H5N1 VLPs had protective levels of HAI antibodies to a representative isolates from each subclade of clade 2. Furthermore, VLP vaccinated animals were completely protected from a lethal challenge of the clade 2.2 H5N1 virus A/Whooper Swan/Mongolia/244/2005. This is the first report describing the use of COBRA-based antigen design. The COBRA HA H5N1 VLP vaccine elicited broadly reactive antibodies and is an effective influenza vaccine against HPAI virus. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/21320540/A_computationally_optimized_broadly_reactive_antigen__COBRA__based_H5N1_VLP_vaccine_elicits_broadly_reactive_antibodies_in_mice_and_ferrets_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(11)00172-1 DB - PRIME DP - Unbound Medicine ER -