Vaccine-Associated Enhanced Respiratory Disease following Influenza Virus Infection in Ferrets Recapitulates the Model in Pigs

Kimble, J. Brian; Wymore Brand, Meghan; Kaplan, Bryan S.; Gauger, Phillip; Coyle, Elizabeth M.; Chilcote, Katarina; Khurana, Surender; Vincent, Amy L.

doi:10.1128/jvi.01725-21

Title: Vaccine-Associated Enhanced Respiratory Disease following Influenza Virus Infection in Ferrets Recapitulates the Model in Pigs

Journal Article · Wed Mar 09 00:00:00 EST 2022 · Journal of Virology

DOI:https://doi.org/10.1128/jvi.01725-21· OSTI ID:1982977

Kimble, J. Brian ^[1]; Wymore Brand, Meghan ^[1]; Kaplan, Bryan S. ^[1];

^[2]; Coyle, Elizabeth M. ^[3]; Chilcote, Katarina ^[3]; Khurana, Surender ^[3];

^[1]

US Dept. of Agriculture (USDA-ARS)., Ames, IA (United States)
Iowa State Univ., Ames, IA (United States)
Food and Drug Administration (FDA), Silver Spring, MD (United States)

Influenza A virus (IAV) causes respiratory disease in swine and humans. Vaccines are used to prevent influenza illness in both populations but must be frequently updated due to rapidly evolving strains. Mismatch between the circulating strains and the strains contained in vaccines may cause loss of efficacy. Whole inactivated virus (WIV) vaccines with adjuvant, utilized by the swine industry, are effective against antigenically similar viruses; however, vaccine-associated enhanced respiratory disease (VAERD) may happen when the WIV is antigenically mismatched with the infecting virus. VAERD is a repeatable model in pigs, but had yet to be experimentally demonstrated in other mammalian species. We recapitulated VAERD in ferrets, a standard benchmark animal model for studying human influenza infection, in a direct comparison to VAERD in pigs. Both species were vaccinated with WIV with oil-in-water adjuvant containing a d -1 H1N2 (1B.2.2) derived from the pre-2009 human seasonal lineage, then challenged with a 2009 pandemic H1N1 (H1N1pdm09, 1A.3.3.2) 5 weeks after vaccination. Nonvaccinated and challenged groups showed typical signs of influenza disease, but the mismatched vaccinated and challenged pigs and ferrets showed elevated clinical signs, despite similar viral loads. VAERD-affected pigs exhibited a 2-fold increase in lung lesions, while VAERDaffected ferrets showed a 4-fold increase. Similar to pigs, antibodies from VAERD-affected ferrets preferentially bound to the HA2 domain of the H1N1pdm09 challenge strain. These results indicate that VAERD is not limited to pigs, as demonstrated here in ferrets, and the need to consider VAERD when evaluating new vaccine platforms and strategies.

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Research Organization:: Oak Ridge Associated Universities (ORAU), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; USDA

Grant/Contract Number:: AC05-06OR23100

OSTI ID:: 1982977

Journal Information:: Journal of Virology, Vol. 96, Issue 5; ISSN 0022-538X

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

An optimized enzyme-linked lectin assay to measure influenza A virus neuraminidase inhibition antibody titers in human sera Couzens, Laura; Gao, Jin; Westgeest, Kim Journal of Virological Methods, Vol. 210 https://doi.org/10.1016/j.jviromet.2014.09.003	journal	December 2014
Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections Kaplan, Bryan S.; Kimble, J. Brian; Chang, Jennifer Journal of Virology, Vol. 94, Issue 16 https://doi.org/10.1128/JVI.01009-20	journal	July 2020
Gene Expression Analysis of Host Innate Immune Responses during Lethal H5N1 Infection in Ferrets Cameron, Cheryl M.; Cameron, Mark J.; Bermejo-Martin, Jesus F. Journal of Virology, Vol. 82, Issue 22 https://doi.org/10.1128/JVI.00691-08	journal	November 2008
A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial Nachbagauer, Raffael; Feser, Jodi; Naficy, Abdollah Nature Medicine, Vol. 27, Issue 1 https://doi.org/10.1038/s41591-020-1118-7	journal	December 2020
Assessment of the Efficacy of Commercially Available and Candidate Vaccines against a Pandemic H1N1 2009 Virus Kobinger, Gary P.; Meunier, Isabelle; Patel, Ami The Journal of Infectious Diseases, Vol. 201, Issue 7 https://doi.org/10.1086/651171	journal	April 2010
Infection enhancement of influenza A H1 subtype viruses in macrophage-like P388D1 cells by cross-reactive antibodies Ochiai, H.; Kurokawa, M.; Kuroki, Y. Journal of Medical Virology, Vol. 30, Issue 4 https://doi.org/10.1002/jmv.1890300406	journal	April 1990
The type of adjuvant in whole inactivated influenza a virus vaccines impacts vaccine-associated enhanced respiratory disease Souza, Carine K.; Rajão, Daniela S.; Sandbulte, Matthew R. Vaccine, Vol. 36, Issue 41 https://doi.org/10.1016/j.vaccine.2018.08.072	journal	October 2018
Vaccine-associated enhanced respiratory disease is influenced by haemagglutinin and neuraminidase in whole inactivated influenza virus vaccines Rajão, Daniela S.; Chen, Hongjun; Perez, Daniel R. Journal of General Virology, Vol. 97, Issue 7 https://doi.org/10.1099/jgv.0.000468	journal	July 2016
Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus Gauger, Phillip C.; Vincent, Amy L.; Loving, Crystal L. Vaccine, Vol. 29, Issue 15 https://doi.org/10.1016/j.vaccine.2011.01.082	journal	March 2011
Human antibody repertoire after VSV-Ebola vaccination identifies novel targets and virus-neutralizing IgM antibodies Khurana, Surender; Fuentes, Sandra; Coyle, Elizabeth M. Nature Medicine, Vol. 22, Issue 12 https://doi.org/10.1038/nm.4201	journal	October 2016
Efficacy of inactivated swine influenza virus vaccines against the 2009 A/H1N1 influenza virus in pigs Vincent, Amy L.; Ciacci-Zanella, Janice R.; Lorusso, Alessio Vaccine, Vol. 28, Issue 15 https://doi.org/10.1016/j.vaccine.2010.01.049	journal	March 2010
Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia Nature Medicine, Vol. 17, Issue 2 https://doi.org/10.1038/nm.2262	journal	December 2010
Vaccination of pigs with a DNA construct expressing an influenza virus M2–nucleoprotein fusion protein exacerbates disease after challenge with influenza A virus Heinen, Paul P.; Rijsewijk, Frans A.; de Boer-Luijtze, Els A. Journal of General Virology, Vol. 83, Issue 8 https://doi.org/10.1099/0022-1317-83-8-1851	journal	August 2002
Live Attenuated Influenza Vaccine Provides Superior Protection from Heterologous Infection in Pigs with Maternal Antibodies without Inducing Vaccine-Associated Enhanced Respiratory Disease Vincent, Amy L.; Ma, Wenjun; Lager, Kelly M. Journal of Virology, Vol. 86, Issue 19 https://doi.org/10.1128/JVI.01439-12	journal	October 2012
Infection enhancement of influenza A NWS virus in primary murine macrophages by anti-hemagglutinin monoclonal antibody Ochiai, Hiroshi; Kurokawa, Masahiko; Matsui, Shoko Journal of Medical Virology, Vol. 36, Issue 3 https://doi.org/10.1002/jmv.1890360312	journal	March 1992
Transmissibility of Variant Influenza From Swine to Humans: A Modeling Approach Wong, Karen K.; Gambhir, Manoj; Finelli, Lyn Clinical Infectious Diseases, Vol. 57, Issue suppl_1 https://doi.org/10.1093/cid/cit303	journal	July 2013
The global antigenic diversity of swine influenza A viruses Lewis, Nicola S.; Russell, Colin A.; Langat, Pinky eLife, Vol. 5 https://doi.org/10.7554/eLife.12217	journal	April 2016
Vaccine-Induced Anti-HA2 Antibodies Promote Virus Fusion and Enhance Influenza Virus Respiratory Disease Khurana, Surender; Loving, Crystal L.; Manischewitz, Jody Science Translational Medicine, Vol. 5, Issue 200 https://doi.org/10.1126/scitranslmed.3006366	journal	August 2013
High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza To, Kelvin K. W.; Zhang, Anna J. X.; Hung, Ivan F. N. Clinical and Vaccine Immunology, Vol. 19, Issue 7 https://doi.org/10.1128/CVI.00081-12	journal	May 2012
Viral-Induced Enhanced Disease Illness Smatti, Maria K.; Al Thani, Asmaa A.; Yassine, Hadi M. Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.02991	journal	December 2018
Adjuvanted influenza vaccines Tregoning, John S.; Russell, Ryan F.; Kinnear, Ekaterina Human Vaccines & Immunotherapeutics, Vol. 14, Issue 3 https://doi.org/10.1080/21645515.2017.1415684	journal	January 2018
Severity of Clinical Disease and Pathology in Ferrets Experimentally Infected with Influenza Viruses Is Influenced by Inoculum Volume Moore, Ian N.; Lamirande, Elaine W.; Paskel, Myeisha Journal of Virology, Vol. 88, Issue 23 https://doi.org/10.1128/JVI.02341-14	journal	December 2014
Regional patterns of genetic diversity in swine influenza A viruses in the United States from 2010 to 2016 Walia, Rasna R.; Anderson, Tavis K.; Vincent, Amy L. Influenza and Other Respiratory Viruses, Vol. 13, Issue 3 https://doi.org/10.1111/irv.12559	journal	January 2019
Enhancement of the Infectivity of Arboviruses by Specific Antisera Produced in Domestic Fowls Hawkes, Ra Australian Journal of Experimental Biology and Medical Science, Vol. 42, Issue 4 https://doi.org/10.1038/icb.1964.44	journal	August 1964
Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into Swine in the United States, 2009 to 2014 Nelson, Martha I.; Stratton, Jered; Killian, Mary Lea Journal of Virology, Vol. 89, Issue 12 https://doi.org/10.1128/JVI.00459-15	journal	April 2015
Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans Khurana, Surender; Hahn, Megan; Coyle, Elizabeth M. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11296-5	journal	July 2019
ISU FLUture: a veterinary diagnostic laboratory web-based platform to monitor the temporal genetic patterns of Influenza A virus in swine Zeller, Michael A.; Anderson, Tavis K.; Walia, Rasna W. BMC Bioinformatics, Vol. 19, Issue 1 https://doi.org/10.1186/s12859-018-2408-7	journal	November 2018
Vaccine-Associated Enhanced Respiratory Disease Does Not Interfere with the Adaptive Immune Response Following Challenge with Pandemic A/H1N1 2009 Gauger, Phillip C.; Loving, Crystal L.; Lager, Kelly M. Viral Immunology, Vol. 26, Issue 5 https://doi.org/10.1089/vim.2013.0018	journal	October 2013
Failure of protection and enhanced pneumonia with a US H1N2 swine influenza virus in pigs vaccinated with an inactivated classical swine H1N1 vaccine Vincent, Amy L.; Lager, Kelly M.; Janke, Bruce H. Veterinary Microbiology, Vol. 126, Issue 4 https://doi.org/10.1016/j.vetmic.2007.07.011	journal	January 2008
MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines Khurana, Surender; Verma, Nitin; Yewdell, Jonathan W. Science Translational Medicine, Vol. 3, Issue 85 https://doi.org/10.1126/scitranslmed.3002336	journal	June 2011
Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada Skowronski, Danuta M.; De Serres, Gaston; Crowcroft, Natasha S. PLoS Medicine, Vol. 7, Issue 4 https://doi.org/10.1371/journal.pmed.1000258	journal	April 2010
Human Infections With Influenza A(H3N2) Variant Virus in the United States, 2011-2012 Epperson, S.; Jhung, M.; Richards, S. Clinical Infectious Diseases, Vol. 57, Issue suppl 1 https://doi.org/10.1093/cid/cit272	journal	June 2013
Efficacy in Pigs of Inactivated and Live Attenuated Influenza Virus Vaccines against Infection and Transmission of an Emerging H3N2 Similar to the 2011-2012 H3N2v Loving, C. L.; Lager, K. M.; Vincent, A. L. Journal of Virology, Vol. 87, Issue 17 https://doi.org/10.1128/JVI.01038-13	journal	July 2013
Influenza A virus hemagglutinin protein subunit vaccine elicits vaccine-associated enhanced respiratory disease in pigs Rajão, Daniela S.; Loving, Crystal L.; Gauger, Phillip C. Vaccine, Vol. 32, Issue 40 https://doi.org/10.1016/j.vaccine.2014.07.059	journal	September 2014
Comparison of the Pathogenicity of Two US Porcine Reproductive and Respiratory Syndrome Virus Isolates with that of the Lelystad Virus Halbur, P. G.; Paul, P. S.; Frey, M. L. Veterinary Pathology, Vol. 32, Issue 6 https://doi.org/10.1177/030098589503200606	journal	November 1995
Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk Skowronski, Danuta M.; Hamelin, Marie-Eve; De Serres, Gaston PLoS ONE, Vol. 9, Issue 1 https://doi.org/10.1371/journal.pone.0086555	journal	January 2014
Outbreak of Variant Influenza A(H3N2) Virus in the United States Jhung, M. A.; Epperson, S.; Biggerstaff, M. Clinical Infectious Diseases, Vol. 57, Issue 12 https://doi.org/10.1093/cid/cit649	journal	September 2013
Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics Winarski, Katie L.; Tang, Juanjie; Klenow, Laura Proceedings of the National Academy of Sciences, Vol. 116, Issue 30 https://doi.org/10.1073/pnas.1821317116	journal	July 2019
Kinetics of Lung Lesion Development and Pro-Inflammatory Cytokine Response in Pigs With Vaccine-Associated Enhanced Respiratory Disease Induced by Challenge With Pandemic (2009) A/H1N1 Influenza Virus Gauger, P. C.; Vincent, A. L.; Loving, C. L. Veterinary Pathology, Vol. 49, Issue 6 https://doi.org/10.1177/0300985812439724	journal	March 2012
Swine influenza matrix 2 (M2) protein contributes to protection against infection with different H1 swine influenza virus (SIV) isolates Kitikoon, Pravina; Vincent, Amy L.; Janke, Bruce H. Vaccine, Vol. 28, Issue 2 https://doi.org/10.1016/j.vaccine.2009.09.130	journal	December 2009
Influenza imprinting in childhood and the influence on vaccine response later in life Kelvin, Alyson A.; Zambon, Maria Eurosurveillance, Vol. 24, Issue 48 https://doi.org/10.2807/1560-7917.ES.2019.24.48.1900720	journal	November 2019
Association Between Seasonal Influenza Vaccination in 2008–2009 and Pandemic Influenza A (H1N1) 2009 Infection Among School Students From Kobe, Japan, April–June 2009 Tsuchihashi, Yuuki; Sunagawa, Tomimasa; Yahata, Yuichiro Clinical Infectious Diseases, Vol. 54, Issue 3 https://doi.org/10.1093/cid/cir787	journal	November 2011
Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States Vincent, Amy L.; Lager, Kelly M.; Ma, Wenjun Veterinary Microbiology, Vol. 118, Issue 3-4 https://doi.org/10.1016/j.vetmic.2006.07.017	journal	December 2006
Antibody-mediated growth of influenza A NWS virus in macrophagelike cell line P388D1 Ochiai, H.; Kurokawa, M.; Hayashi, K. Journal of Virology, Vol. 62, Issue 1 https://doi.org/10.1128/JVI.62.1.20-26.1988	journal	January 1988
Respiratory Syncytial Virus Disease in Infants Despite Prior Administration of Antigenic Inactivated Vaccine12 Kim, Hyun Wha; Canchola, Jose G.; Brandt, Carl D. American Journal of Epidemiology, Vol. 89, Issue 4 https://doi.org/10.1093/oxfordjournals.aje.a120955	journal	April 1969
Age at Vaccination and Timing of Infection Do Not Alter Vaccine-Associated Enhanced Respiratory Disease in Influenza A Virus-Infected Pigs Souza, Carine K.; Rajão, Daniela S.; Loving, Crystal L. Clinical and Vaccine Immunology, Vol. 23, Issue 6 https://doi.org/10.1128/CVI.00563-15	journal	June 2016
Eight-plasmid system for rapid generation of influenza virus vaccines Hoffmann, E. Vaccine, Vol. 20, Issue 25-26 https://doi.org/10.1016/S0264-410X(02)00268-2	journal	August 2002
A Simple Method of Estimating Fifty per cent Endpoints12 Reed, L. J.; Muench, H. American Journal of Epidemiology, Vol. 27, Issue 3 https://doi.org/10.1093/oxfordjournals.aje.a118408	journal	May 1938
Primary Influenza A Virus Infection Induces Cross-Reactive Antibodies thatEnhance Uptake of Virus into Fc Receptor-Bearing Cells Gotoff, R.; Tamura, M.; Janus, J. Journal of Infectious Diseases, Vol. 169, Issue 1 https://doi.org/10.1093/infdis/169.1.200	journal	January 1994
Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease Gauger, Phillip C.; Loving, Crystal L.; Khurana, Surender Virology, Vol. 471-473 https://doi.org/10.1016/j.virol.2014.10.003	journal	December 2014

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Title: Vaccine-Associated Enhanced Respiratory Disease following Influenza Virus Infection in Ferrets Recapitulates the Model in Pigs

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