tetano
Editor, Senior Moderator
Mol Ther
. 2022 Jan 6;S1525-0016(22)00011-9.
doi: 10.1016/j.ymthe.2022.01.011. Online ahead of print.
A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice
Carly M Bliss[SUP] 1 [/SUP], Alec W Freyn[SUP] 1 [/SUP], Tom G Caniels[SUP] 1 [/SUP], Victor H Leyva-Grado[SUP] 1 [/SUP], Raffael Nachbagauer[SUP] 1 [/SUP], Weina Sun[SUP] 1 [/SUP], Gene S Tan[SUP] 2 [/SUP], Virginia L Gillespie[SUP] 3 [/SUP], Meagan McMahon[SUP] 1 [/SUP], Florian Krammer[SUP] 4 [/SUP], Adrian Vs Hill[SUP] 5 [/SUP], Peter Palese[SUP] 1 [/SUP], Lynda Coughlan[SUP] 6 [/SUP]
Affiliations
Abstract
Conventional influenza vaccines fail to confer broad protection against diverse influenza A viruses with pandemic potential. Efforts to develop a universal influenza virus vaccine include refocusing immunity towards the highly conserved stalk domain of the influenza virus surface glycoprotein, hemagglutinin (HA). We constructed a non-replicating adenoviral (Ad) vector, encoding a secreted form of H1 HA, to evaluate HA stalk-focused immunity. The Ad5_H1 vaccine was tested in mice for its ability to elicit broad, cross-reactive protection against homologous, heterologous and heterosubtypic lethal challenge, in a single-shot immunization regimen. Ad5_H1 elicited hemagglutination inhibition (HI[SUP]+[/SUP]) active antibodies (Abs), which conferred 100% sterilizing protection from homologous H1N1 challenge. Furthermore, Ad5_H1 rapidly induced H1 stalk-specific Abs with Fc-mediated effector function activity, in addition to stimulating both CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] stalk-specific T cell responses. This phenotype of immunity provided 100% protection from lethal challenge with a head-mismatched, reassortant influenza virus bearing a chimeric HA, cH6/1, in a stalk-mediated manner. Most importantly, 100% protection from mortality following lethal challenge with a heterosubtypic avian influenza virus, H5N1, was observed following a single immunization with Ad5_H1. In conclusion, Ad-based influenza vaccines can elicit significant breadth of protection in naïve animals and could be considered for pandemic preparedness and stockpiling.
. 2022 Jan 6;S1525-0016(22)00011-9.
doi: 10.1016/j.ymthe.2022.01.011. Online ahead of print.
A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice
Carly M Bliss[SUP] 1 [/SUP], Alec W Freyn[SUP] 1 [/SUP], Tom G Caniels[SUP] 1 [/SUP], Victor H Leyva-Grado[SUP] 1 [/SUP], Raffael Nachbagauer[SUP] 1 [/SUP], Weina Sun[SUP] 1 [/SUP], Gene S Tan[SUP] 2 [/SUP], Virginia L Gillespie[SUP] 3 [/SUP], Meagan McMahon[SUP] 1 [/SUP], Florian Krammer[SUP] 4 [/SUP], Adrian Vs Hill[SUP] 5 [/SUP], Peter Palese[SUP] 1 [/SUP], Lynda Coughlan[SUP] 6 [/SUP]
Affiliations
- PMID: 34999208
- DOI: 10.1016/j.ymthe.2022.01.011
Abstract
Conventional influenza vaccines fail to confer broad protection against diverse influenza A viruses with pandemic potential. Efforts to develop a universal influenza virus vaccine include refocusing immunity towards the highly conserved stalk domain of the influenza virus surface glycoprotein, hemagglutinin (HA). We constructed a non-replicating adenoviral (Ad) vector, encoding a secreted form of H1 HA, to evaluate HA stalk-focused immunity. The Ad5_H1 vaccine was tested in mice for its ability to elicit broad, cross-reactive protection against homologous, heterologous and heterosubtypic lethal challenge, in a single-shot immunization regimen. Ad5_H1 elicited hemagglutination inhibition (HI[SUP]+[/SUP]) active antibodies (Abs), which conferred 100% sterilizing protection from homologous H1N1 challenge. Furthermore, Ad5_H1 rapidly induced H1 stalk-specific Abs with Fc-mediated effector function activity, in addition to stimulating both CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] stalk-specific T cell responses. This phenotype of immunity provided 100% protection from lethal challenge with a head-mismatched, reassortant influenza virus bearing a chimeric HA, cH6/1, in a stalk-mediated manner. Most importantly, 100% protection from mortality following lethal challenge with a heterosubtypic avian influenza virus, H5N1, was observed following a single immunization with Ad5_H1. In conclusion, Ad-based influenza vaccines can elicit significant breadth of protection in naïve animals and could be considered for pandemic preparedness and stockpiling.