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H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses.
Vaccine. 2008 Oct 03; 26(42):5393-9.V

Abstract

In this study, recombinant virus-like particles (VLPs) were evaluated as a candidate vaccine against emerging influenza viruses with pandemic potential. The VLPs are composed of the hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins of the H5N1 A/Indonesia/05/2005 (clade 2.1; [Indo/05]) virus, which were expressed using baculovirus in Spodoptera frugiperda (Sf9) cells. Ferrets received either 2 injections of the VLP vaccine at escalating doses (based on HA content), recombinant HA, or were mock vaccinated. Vaccinated ferrets were then challenged with either H5N1 Indo/05 or H5N1 A/Viet Nam 1203/2004 (VN/04) wild-type viruses. All ferrets that received the VLP vaccine survived regardless of the VLP dose or challenge strain, whereas seven of eight mock vaccinated ferrets died. The VLP vaccine induced HAI antibodies against the homologous H5N1 clade 2.1 strain, as well as heterologous strains from H5N1 clades 1, 2.2, and 2.3. The magnitude of the HAI titers correlated with VLP dose. Neutralizing antibody responses against the Indo/05 and VN/04 strains showed a similar pattern. Affinity of the anti-HA antibodies raised by the H5N1 Indo/05 VLPs had a higher association rate to the homologous clade 2.1 HA than to the clade 1 (VN/04) HA; however, once bound, antibodies had similar slow disassociation rates. These results provide support for continued development of the H5N1 VLPs as a candidate vaccine against pandemic influenza. Exploration of immunologic correlates of protection for H5N1 vaccines beyond HAI and neutralizing antibody responses is warranted.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Mahmood K
Novavax, Inc., Rockville, MD, USA.
Bright RA
No affiliation info available
Mytle N
No affiliation info available
Carter DM
No affiliation info available
Crevar CJ
No affiliation info available
Achenbach JE
No affiliation info available
Heaton PM
No affiliation info available
Tumpey TM
No affiliation info available
Ross TM
No affiliation info available

MeSH

AnimalsAntibodies, ViralBaculoviridaeCross ReactionsFerretsHemagglutination Inhibition TestsHemagglutinin Glycoproteins, Influenza VirusInfluenza A Virus, H5N1 SubtypeInfluenza VaccinesNeuraminidaseNeutralization TestsOrthomyxoviridae Infections

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18706956

Citation

Mahmood, Kutubuddin, et al. "H5N1 VLP Vaccine Induced Protection in Ferrets Against Lethal Challenge With Highly Pathogenic H5N1 Influenza Viruses." Vaccine, vol. 26, no. 42, 2008, pp. 5393-9.
Mahmood K, Bright RA, Mytle N, et al. H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses. Vaccine. 2008;26(42):5393-9.
Mahmood, K., Bright, R. A., Mytle, N., Carter, D. M., Crevar, C. J., Achenbach, J. E., Heaton, P. M., Tumpey, T. M., & Ross, T. M. (2008). H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses. Vaccine, 26(42), 5393-9. https://doi.org/10.1016/j.vaccine.2008.07.084
Mahmood K, et al. H5N1 VLP Vaccine Induced Protection in Ferrets Against Lethal Challenge With Highly Pathogenic H5N1 Influenza Viruses. Vaccine. 2008 Oct 3;26(42):5393-9. PubMed PMID: 18706956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses. AU - Mahmood,Kutubuddin, AU - Bright,Rick A, AU - Mytle,Nutan, AU - Carter,Donald M, AU - Crevar,Corey J, AU - Achenbach,Jenna E, AU - Heaton,Penny M, AU - Tumpey,Terrence M, AU - Ross,Ted M, Y1 - 2008/08/14/ PY - 2008/05/25/received PY - 2008/07/24/revised PY - 2008/07/29/accepted PY - 2008/8/19/pubmed PY - 2008/11/19/medline PY - 2008/8/19/entrez SP - 5393 EP - 9 JF - Vaccine JO - Vaccine VL - 26 IS - 42 N2 - In this study, recombinant virus-like particles (VLPs) were evaluated as a candidate vaccine against emerging influenza viruses with pandemic potential. The VLPs are composed of the hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins of the H5N1 A/Indonesia/05/2005 (clade 2.1; [Indo/05]) virus, which were expressed using baculovirus in Spodoptera frugiperda (Sf9) cells. Ferrets received either 2 injections of the VLP vaccine at escalating doses (based on HA content), recombinant HA, or were mock vaccinated. Vaccinated ferrets were then challenged with either H5N1 Indo/05 or H5N1 A/Viet Nam 1203/2004 (VN/04) wild-type viruses. All ferrets that received the VLP vaccine survived regardless of the VLP dose or challenge strain, whereas seven of eight mock vaccinated ferrets died. The VLP vaccine induced HAI antibodies against the homologous H5N1 clade 2.1 strain, as well as heterologous strains from H5N1 clades 1, 2.2, and 2.3. The magnitude of the HAI titers correlated with VLP dose. Neutralizing antibody responses against the Indo/05 and VN/04 strains showed a similar pattern. Affinity of the anti-HA antibodies raised by the H5N1 Indo/05 VLPs had a higher association rate to the homologous clade 2.1 HA than to the clade 1 (VN/04) HA; however, once bound, antibodies had similar slow disassociation rates. These results provide support for continued development of the H5N1 VLPs as a candidate vaccine against pandemic influenza. Exploration of immunologic correlates of protection for H5N1 vaccines beyond HAI and neutralizing antibody responses is warranted. SN - 0264-410X UR - https://www.unboundmedicine.com/medline/citation/18706956/H5N1_VLP_vaccine_induced_protection_in_ferrets_against_lethal_challenge_with_highly_pathogenic_H5N1_influenza_viruses_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓60]

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