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Recombinant H5 hemagglutinin adjuvanted with nanoemulsion protects ferrets against pathogenic avian influenza virus challenge.
Vaccine. 2019 03 14; 37(12):1591-1600.V

Abstract

BACKGROUND

Highly pathogenic H5N1 influenza viruses remain a pandemic risk to the world population. Although vaccines are the best solution to prevent this threat, a more effective vaccine for H5 strains of influenza has yet to be developed. All existing vaccines target only serum antibody against influenza as the primary outcome, while mucosal immunity has not been addressed. To address these shortcomings we have used an effective mucosal adjuvant system to produce a prototype vaccine that provides antibody, cellular and mucosal immunity to multiple serotypes of H5.

METHODS

Plant-derived recombinant H5 (rH5) antigen was mixed with a novel nanoemulsion NE01 adjuvant. The rH5-NE01 vaccine was administered intranasally to CD-1 mice and ferrets. Immunogenicity of this immunization was evaluated through rH5-specific antibody and cellular immune responses. Hemagglutination inhibition (HI) and virus neutralization (VN) assays were performed. Protection against H5N1 virus challenge was evaluated in ferrets.

RESULTS

Intranasal immunization with rH5-NE01vaccine induced high titers (>106) of rH5-specific IgG in mice. In mice and ferrets this vaccine also achieved titers of ≥40 for both HI and VN. Additionally, the levels of rH5-specific IgA were significantly increased in bronchial secretions in these animals. The rH5-NE01 vaccine enhanced rH5-specific cellular immune responses including IFN-γ and IL-17. Ten-day survival post challenge was 100% in ferrets that received rH5-NE01compared to 12.5% in the PBS group. Furthermore, this vaccine prevented weight loss and increases in body temperature after H5N1 challenge as compared to the controls. Moreover, H5N1 virus in nasal wash of rH5-NE01-vaccinated ferrets was significantly decreased compared to controls.

CONCLUSION

Intranasal immunization with rH5 antigen formulated with NE01 adjuvant elicited strong, broad and balanced immune responses that effectively protect against H5N1 influenza virus infection in the ferret model. The ease of formulation of rH5-NE01 makes this novel combination a promising mucosal vaccine candidate for pandemic influenza.

Authors+Show Affiliations

University of Michigan, Michigan Nanotechnology Institute for Medicine and Biological Sciences (M-NIMBs), Ann Arbor, MI, United States. Electronic address: shidasui@umich.edu.BlueWillow Biologic, Ann Arbor, MI, United States.University of Michigan, Michigan Nanotechnology Institute for Medicine and Biological Sciences (M-NIMBs), Ann Arbor, MI, United States.University of Michigan, Michigan Nanotechnology Institute for Medicine and Biological Sciences (M-NIMBs), Ann Arbor, MI, United States.BlueWillow Biologic, Ann Arbor, MI, United States.Fraunhofer USA Center for Molecular Biotechnology (FhCMB), Newark, DE, United States.Fraunhofer USA Center for Molecular Biotechnology (FhCMB), Newark, DE, United States.Fraunhofer USA Center for Molecular Biotechnology (FhCMB), Newark, DE, United States.BlueWillow Biologic, Ann Arbor, MI, United States.University of Michigan, Michigan Nanotechnology Institute for Medicine and Biological Sciences (M-NIMBs), Ann Arbor, MI, United States.

Pub Type(s)

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

Language

eng

PubMed ID

30795941

Citation

Wang, Su He, et al. "Recombinant H5 Hemagglutinin Adjuvanted With Nanoemulsion Protects Ferrets Against Pathogenic Avian Influenza Virus Challenge." Vaccine, vol. 37, no. 12, 2019, pp. 1591-1600.
Wang SH, Smith D, Cao Z, et al. Recombinant H5 hemagglutinin adjuvanted with nanoemulsion protects ferrets against pathogenic avian influenza virus challenge. Vaccine. 2019;37(12):1591-1600.
Wang, S. H., Smith, D., Cao, Z., Chen, J., Acosta, H., Chichester, J. A., Yusibov, V., Streatfield, S. J., Fattom, A., & Baker, J. R. (2019). Recombinant H5 hemagglutinin adjuvanted with nanoemulsion protects ferrets against pathogenic avian influenza virus challenge. Vaccine, 37(12), 1591-1600. https://doi.org/10.1016/j.vaccine.2019.02.002
Wang SH, et al. Recombinant H5 Hemagglutinin Adjuvanted With Nanoemulsion Protects Ferrets Against Pathogenic Avian Influenza Virus Challenge. Vaccine. 2019 03 14;37(12):1591-1600. PubMed PMID: 30795941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant H5 hemagglutinin adjuvanted with nanoemulsion protects ferrets against pathogenic avian influenza virus challenge. AU - Wang,Su He, AU - Smith,Douglas, AU - Cao,Zhengyi, AU - Chen,Jesse, AU - Acosta,Hugo, AU - Chichester,Jessica A, AU - Yusibov,Vidadi, AU - Streatfield,Stephen J, AU - Fattom,Ali, AU - Baker,James R,Jr Y1 - 2019/02/19/ PY - 2018/09/25/received PY - 2019/01/31/revised PY - 2019/02/02/accepted PY - 2019/2/24/pubmed PY - 2020/7/1/medline PY - 2019/2/24/entrez KW - Ferrets KW - H5N1 KW - Mice KW - Nanoemulsion KW - Vaccine SP - 1591 EP - 1600 JF - Vaccine JO - Vaccine VL - 37 IS - 12 N2 - BACKGROUND: Highly pathogenic H5N1 influenza viruses remain a pandemic risk to the world population. Although vaccines are the best solution to prevent this threat, a more effective vaccine for H5 strains of influenza has yet to be developed. All existing vaccines target only serum antibody against influenza as the primary outcome, while mucosal immunity has not been addressed. To address these shortcomings we have used an effective mucosal adjuvant system to produce a prototype vaccine that provides antibody, cellular and mucosal immunity to multiple serotypes of H5. METHODS: Plant-derived recombinant H5 (rH5) antigen was mixed with a novel nanoemulsion NE01 adjuvant. The rH5-NE01 vaccine was administered intranasally to CD-1 mice and ferrets. Immunogenicity of this immunization was evaluated through rH5-specific antibody and cellular immune responses. Hemagglutination inhibition (HI) and virus neutralization (VN) assays were performed. Protection against H5N1 virus challenge was evaluated in ferrets. RESULTS: Intranasal immunization with rH5-NE01vaccine induced high titers (>106) of rH5-specific IgG in mice. In mice and ferrets this vaccine also achieved titers of ≥40 for both HI and VN. Additionally, the levels of rH5-specific IgA were significantly increased in bronchial secretions in these animals. The rH5-NE01 vaccine enhanced rH5-specific cellular immune responses including IFN-γ and IL-17. Ten-day survival post challenge was 100% in ferrets that received rH5-NE01compared to 12.5% in the PBS group. Furthermore, this vaccine prevented weight loss and increases in body temperature after H5N1 challenge as compared to the controls. Moreover, H5N1 virus in nasal wash of rH5-NE01-vaccinated ferrets was significantly decreased compared to controls. CONCLUSION: Intranasal immunization with rH5 antigen formulated with NE01 adjuvant elicited strong, broad and balanced immune responses that effectively protect against H5N1 influenza virus infection in the ferret model. The ease of formulation of rH5-NE01 makes this novel combination a promising mucosal vaccine candidate for pandemic influenza. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/30795941/Recombinant_H5_hemagglutinin_adjuvanted_with_nanoemulsion_protects_ferrets_against_pathogenic_avian_influenza_virus_challenge_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(19)30168-9 DB - PRIME DP - Unbound Medicine ER -