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­Refined Semi-Lethal H5N1 Influenza Model Through Aerosolized Virus Infection in Macaques

35 Pages Posted: 3 Jul 2023 Publication Status: Published

See all articles by Masaru Kanekiyo

Masaru Kanekiyo

Government of the United States of America - Vaccine Research Center

Rebecca A. Gillespie

Government of the United States of America - Vaccine Research Center

Morgan Midgett

University of Pittsburgh - Center for Vaccine Research

Katherine J. O'Malley

University of Pittsburgh - Center for Vaccine Research

Connor Williams

University of Pittsburgh - Center for Vaccine Research

Syed M. Moin

Government of the United States of America - Vaccine Research Center

Megan Wallace

University of Pittsburgh - Department of Infectious Diseases and Microbiology

Luke Treaster

University of Pittsburgh - Division of Cardiothoracic Imaging

Kristine Cooper

University of Pittsburgh - Department of Biostatistics

Hubza Z. Syeda

Government of the United States of America - Vaccine Research Center

Gwenddolen Kettenburg

University of Pittsburgh - Department of Infectious Diseases and Microbiology

Hasala Rannulu

University of Pittsburgh - Center for Vaccine Research

Adebimpe Obadan

University of Georgia - Department of Population Health

Priscila M. S. Castanha

University of Pittsburgh - Department of Infectious Diseases and Microbiology

Jacqueline Corry

The Ohio State University

Mengying Xia

University of Pittsburgh - Center for Vaccine Research

Emily Olsen

University of Pittsburgh - Center for Vaccine Research

Daniel R. Perez

University of Georgia - Department of Population Health

Gabin Yun

University of Pittsburgh - Division of Cardiothoracic Imaging

Barney S. Graham

University of Pittsburgh - Center for Vaccine Research

Simon M. Barratt-Boyes

University of Pittsburgh - Department of Infectious Diseases and Microbiology

Douglas Reed

University of Pittsburgh - Center for Vaccine Research

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Abstract

Highly pathogenic avian influenza A (HPAI) H5N1 viruses can cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we refined a previously established model of lethal H5N1 infection in cynomolgus macaques and show that repeated vaccination of adjuvanted commercial quadrivalent influenza vaccine confers protection against lethality using the model. We determined that an inhaled aerosol virus dose of 5.1 log10 pfu induced a strong febrile response, acute respiratory distress, with 4 out of 6 naïve cynomolgus macaques succumbing between 4-6 days after challenge, establishing a semi-lethal severe influenza disease model for studying protective countermeasures. Macaques vaccinated with three doses of adjuvanted licensed seasonal quadrivalent influenza vaccine elicited neutralizing antibody response to H1N1 and to a lesser extent, H5N1. All 6 vaccinated macaques survived an inhaled dose of 5.7 log10 pfu (~4 LD50) H5N1 while 4 of 6 unvaccinated control macaques succumbed to lethal disease. Although vaccination did not protect against severe disease, vaccinees developed a significantly milder fever, reduced respiratory disease, and had lower viral load in bronchoalveolar lavage compared to controls. We anticipate that our macaque model will play a vital role in evaluating vaccines and antivirals against influenza pandemics.

Note:
Funding Information: This work was supported in part by the National Institutes of Health and the Leidos Foundation, contract number HHSN261201500003I; and Intramural Research Program of the Vaccine Research Center, NIAID, NIH.

Declaration of Interests: The authors declare no conflict of interest.

Ethical Approval Statement: All experiments were conducted in compliance with the Animal Welfare Act and other Federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996, and approved by the Institutional Animal Care and Use Committee. The facility where the study was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International.

Keywords: Influenza, nonhuman primate, NHP, H5N1, cynomolgus macaque, animal model, aerosol, vaccine, HPAI, pandemic

Suggested Citation

Kanekiyo, Masaru and Gillespie, Rebecca A. and Midgett, Morgan and O'Malley, Katherine J. and Williams, Connor and Moin, Syed M. and Wallace, Megan and Treaster, Luke and Cooper, Kristine and Syeda, Hubza Z. and Kettenburg, Gwenddolen and Rannulu, Hasala and Obadan, Adebimpe and Castanha, Priscila M. S. and Corry, Jacqueline and Xia, Mengying and Olsen, Emily and Perez, Daniel R. and Yun, Gabin and Graham, Barney S. and Barratt-Boyes, Simon M. and Administrator, Sneak Peek and Reed, Douglas, ­Refined Semi-Lethal H5N1 Influenza Model Through Aerosolized Virus Infection in Macaques. Available at SSRN: https://ssrn.com/abstract=4495665 or http://dx.doi.org/10.2139/ssrn.4495665
This version of the paper has not been formally peer reviewed.

Masaru Kanekiyo

Government of the United States of America - Vaccine Research Center ( email )

Rebecca A. Gillespie

Government of the United States of America - Vaccine Research Center ( email )

Morgan Midgett

University of Pittsburgh - Center for Vaccine Research ( email )

Katherine J. O'Malley

University of Pittsburgh - Center for Vaccine Research ( email )

Connor Williams

University of Pittsburgh - Center for Vaccine Research ( email )

Syed M. Moin

Government of the United States of America - Vaccine Research Center ( email )

Megan Wallace

University of Pittsburgh - Department of Infectious Diseases and Microbiology ( email )

Luke Treaster

University of Pittsburgh - Division of Cardiothoracic Imaging ( email )

Kristine Cooper

University of Pittsburgh - Department of Biostatistics ( email )

Hubza Z. Syeda

Government of the United States of America - Vaccine Research Center ( email )

Gwenddolen Kettenburg

University of Pittsburgh - Department of Infectious Diseases and Microbiology ( email )

Hasala Rannulu

University of Pittsburgh - Center for Vaccine Research ( email )

Adebimpe Obadan

University of Georgia - Department of Population Health ( email )

Priscila M. S. Castanha

University of Pittsburgh - Department of Infectious Diseases and Microbiology ( email )

Jacqueline Corry

The Ohio State University ( email )

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Mengying Xia

University of Pittsburgh - Center for Vaccine Research

Emily Olsen

University of Pittsburgh - Center for Vaccine Research ( email )

Daniel R. Perez

University of Georgia - Department of Population Health ( email )

Gabin Yun

University of Pittsburgh - Division of Cardiothoracic Imaging ( email )

Barney S. Graham

University of Pittsburgh - Center for Vaccine Research ( email )

Simon M. Barratt-Boyes

University of Pittsburgh - Department of Infectious Diseases and Microbiology ( email )

Douglas Reed (Contact Author)

University of Pittsburgh - Center for Vaccine Research ( email )

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