tetano
Editor, Senior Moderator
J Virol
. 2022 Jan 5;JVI0172521.
doi: 10.1128/JVI.01725-21. Online ahead of print.
Vaccine-associated enhanced respiratory disease following influenza virus infection in ferrets recapitulates the model in pigs
J Brian Kimble[SUP] 1 [/SUP], Meghan Wymore Brand[SUP] 1 [/SUP], Bryan S Kaplan[SUP] 1 [/SUP], Phillip Gauger[SUP] 2 [/SUP], Elizabeth M Coyle[SUP] 3 [/SUP], Katarina Chilcote[SUP] 3 [/SUP], Surender Khurana[SUP] 3 [/SUP], Amy L Vincent[SUP] 1 [/SUP]
Affiliations
Abstract
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 strains contained in vaccines may cause loss in 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 δ-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) five 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 VAERD affected 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 VAERD is not limited to pigs, as demonstrated here in ferrets, and the need to consider VAERD when evaluating new vaccine platforms and strategies. Importance We demonstrated the susceptibility of ferrets, a laboratory model species for human influenza A virus research, to vaccine associated enhanced respiratory disease (VAERD) using an experimental model previously demonstrated in pigs. Ferrets developed clinical characteristics of VAERD very similar to that in pigs. The hemagglutinin (HA) stalk is a potential vaccine target to develop more efficacious, broadly reactive influenza vaccine platforms and strategies. However, non-neutralizing antibodies directed towards a conserved epitope on the HA stalk induced by an oil-in-water adjuvanted whole influenza virus vaccine were previously shown in VAERD-affected pigs and were also identified here in VAERD-affected ferrets. The induction of VAERD in ferrets highlights the potential risk of mismatched influenza vaccines to humans and the need to consider VAERD when designing and evaluating vaccine strategies.
. 2022 Jan 5;JVI0172521.
doi: 10.1128/JVI.01725-21. Online ahead of print.
Vaccine-associated enhanced respiratory disease following influenza virus infection in ferrets recapitulates the model in pigs
J Brian Kimble[SUP] 1 [/SUP], Meghan Wymore Brand[SUP] 1 [/SUP], Bryan S Kaplan[SUP] 1 [/SUP], Phillip Gauger[SUP] 2 [/SUP], Elizabeth M Coyle[SUP] 3 [/SUP], Katarina Chilcote[SUP] 3 [/SUP], Surender Khurana[SUP] 3 [/SUP], Amy L Vincent[SUP] 1 [/SUP]
Affiliations
- PMID: 34985999
- DOI: 10.1128/JVI.01725-21
Abstract
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 strains contained in vaccines may cause loss in 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 δ-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) five 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 VAERD affected 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 VAERD is not limited to pigs, as demonstrated here in ferrets, and the need to consider VAERD when evaluating new vaccine platforms and strategies. Importance We demonstrated the susceptibility of ferrets, a laboratory model species for human influenza A virus research, to vaccine associated enhanced respiratory disease (VAERD) using an experimental model previously demonstrated in pigs. Ferrets developed clinical characteristics of VAERD very similar to that in pigs. The hemagglutinin (HA) stalk is a potential vaccine target to develop more efficacious, broadly reactive influenza vaccine platforms and strategies. However, non-neutralizing antibodies directed towards a conserved epitope on the HA stalk induced by an oil-in-water adjuvanted whole influenza virus vaccine were previously shown in VAERD-affected pigs and were also identified here in VAERD-affected ferrets. The induction of VAERD in ferrets highlights the potential risk of mismatched influenza vaccines to humans and the need to consider VAERD when designing and evaluating vaccine strategies.