A direct contact pig influenza challenge model for assessing protective efficacy of monoclonal antibodies

Frontiers in Immunology

Immunology

Alejandro Núñez¹  Fabian Z. X. Lean¹  Basudev Paudyal²  Elma Tchilian²  Adam McNee²  Ronan MacLoughlin³  Philip J. Santangelo⁴  Daryll Vanover⁴  Alain Townsend⁵  Pramila Rijal⁵ 

[1] Department of Pathology, Animal and Plant Health Agency (APHA)-Weybridge, Addlestone, United Kingdom;Host Responses, The Pirbright Institute, Pirbright, United Kingdom;Research and Development, Science and Emerging Technologies, Aerogen Ltd, Galway, Ireland;Wallace H. Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA, United States;Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;

关键词: influenza;    pig;    aerosol delivery;    contact challenge;    transmission;    nasal shedding;    2-12C monoclonal antibody;   

DOI  :  10.3389/fimmu.2023.1229051

 received in 2023-06-28, accepted in 2023-10-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

Monoclonal antibodies (mAbs) can be used to complement immunization for the therapy of influenza virus infection. We have established the pig, a natural large animal host for influenza A, with many physiological, immunological, and anatomical similarities to humans, as an appropriate model for testing mAbs. We have evaluated the protective efficacy of the strongly neutralizing human anti-hemagglutinin mAb, 2-12C in the pig influenza model. Intravenous administration of recombinant 2-12C reduced virus load and lung pathology, however, it did not prevent virus nasal shedding and, consequently, transmission. This may be because the pigs were directly infected intranasally with a high dose of the H1N1pdm09 virus. To address this, we developed a contact challenge model in which the animals were given 2-12C and one day later co-housed with donor pigs previously infected intra-nasally with H1N1pdm09. 2-12C pre-treatment completely prevented infection. We also administered a lower dose of 2-12C by aerosol to the respiratory tract, but this did not prevent shedding in the direct challenge model, although it abolished lung infection. We propose that the direct contact challenge model of pig influenza may be useful for evaluating candidate mAbs and emerging delivery platforms prior to clinical trials.

【 授权许可】

Unknown   
Copyright © 2023 McNee, Vanover, Rijal, Paudyal, Lean, MacLoughlin, Núñez, Townsend, Santangelo and Tchilian