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Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus.
J Immunol. 2016 06 15; 196(12):5014-23.JI

Abstract

Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate.

Authors+Show Affiliations

The Pirbright Institute, Surrey GU24 0NF, United Kingdom;The Pirbright Institute, Surrey GU24 0NF, United Kingdom;School of Veterinary Sciences, University of Bristol, Bristol BS40 5DU, United Kingdom;School of Veterinary Sciences, University of Bristol, Bristol BS40 5DU, United Kingdom;The Pirbright Institute, Surrey GU24 0NF, United Kingdom;The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom;Virology Department, Animal and Plant Health Agency, Weybridge, Surrey KT15 3NB, United Kingdom; and.Virology Department, Animal and Plant Health Agency, Weybridge, Surrey KT15 3NB, United Kingdom; and.School of Veterinary Sciences, University of Bristol, Bristol BS40 5DU, United Kingdom;Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.The Pirbright Institute, Surrey GU24 0NF, United Kingdom;The Pirbright Institute, Surrey GU24 0NF, United Kingdom; elma.tchilian@pirbright.ac.uk.

Pub Type(s)

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

Language

eng

PubMed ID

27183611

Citation

Morgan, Sophie B., et al. "Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged With Pandemic H1N1 Virus." Journal of Immunology (Baltimore, Md. : 1950), vol. 196, no. 12, 2016, pp. 5014-23.
Morgan SB, Hemmink JD, Porter E, et al. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus. J Immunol. 2016;196(12):5014-23.
Morgan, S. B., Hemmink, J. D., Porter, E., Harley, R., Shelton, H., Aramouni, M., Everett, H. E., Brookes, S. M., Bailey, M., Townsend, A. M., Charleston, B., & Tchilian, E. (2016). Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus. Journal of Immunology (Baltimore, Md. : 1950), 196(12), 5014-23. https://doi.org/10.4049/jimmunol.1502632
Morgan SB, et al. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged With Pandemic H1N1 Virus. J Immunol. 2016 06 15;196(12):5014-23. PubMed PMID: 27183611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus. AU - Morgan,Sophie B, AU - Hemmink,Johanneke D, AU - Porter,Emily, AU - Harley,Ross, AU - Shelton,Holly, AU - Aramouni,Mario, AU - Everett,Helen E, AU - Brookes,Sharon M, AU - Bailey,Michael, AU - Townsend,Alain M, AU - Charleston,Bryan, AU - Tchilian,Elma, Y1 - 2016/05/06/ PY - 2015/12/21/received PY - 2016/04/11/accepted PY - 2016/5/17/entrez PY - 2016/5/18/pubmed PY - 2017/8/2/medline SP - 5014 EP - 23 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 196 IS - 12 N2 - Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/27183611/Aerosol_Delivery_of_a_Candidate_Universal_Influenza_Vaccine_Reduces_Viral_Load_in_Pigs_Challenged_with_Pandemic_H1N1_Virus_ DB - PRIME DP - Unbound Medicine ER -