tetano
Editor, Senior Moderator
J Virol. 2018 Nov 14. pii: JVI.00946-18. doi: 10.1128/JVI.00946-18. [Epub ahead of print]
[h=1]Elicitation of protective antibodies against 20 years of future H3N2 co-ciruculating influenza virus variants in ferrets preimmune to historical H3N2 influenza viruses.[/h] Allen JD[SUP]1[/SUP], Jang H[SUP]1[/SUP], DiNapoli J[SUP]2[/SUP], Kleanthous H[SUP]2[/SUP], Ross TM[SUP]3,[/SUP][SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The vast majority of people already have pre-existing immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically na?ve animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 COBRA HA based vaccines boosted pre-existing antibodies induced by wild-type H1N1 virus infections. These H1 COBRA HA antigens induced antibodies with HAI activity against multiple antigenically different H1N1 viral variants. In this study, ferrets, preimmune to historical H3N2 viruses, were vaccinated with virus-like particle (VLP) vaccines expressing either an HA from a wild-type H3 influenza virus or a COBRA H3 HA antigen (T6, T7, T10, or T11). The elicited antisera had the ability to neutralize virus infection against a panel of viruses representing vaccine strains selected by the World Health Organization (WHO), or a set of viral variants that co-circulated during the same time period. Preimmune animals vaccinated with H3 COBRA T10 HA antigen elicited sera with higher HAI antibody titers than antisera elicited by VLP vaccines with wild-type HA VLPs in preimmune ferrets. However, while the T11 COBRA vaccine did not elicit HAI activity, the elicited antibodies did neutralize antigenically distinct H3N2 influenza viruses. Overall, H3 COBRA-based HA vaccines were able to neutralize both historical H3 and comtemporary, as well as future H3N2 viruses with higher titers than vaccines with wild-type H3 HA antigens. This is the first report demonstrating the effectiveness of a broadly reactive H3N3 vaccine in a preimmune ferret model.IMPORTANCE Following influenza virus exposure, the host generates neutralizing anti-hemagglutinin antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, co-circulating strains. The goal of next generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular those that persist over multiple influenza seasons, without requiring an update to the vaccine. To mimic the human condition, COBRA HA virus-like particle vaccines were tested in ferrets that were previously exposed to historical H3N2 influenza viruses. In this model, these vaccines elicited broadly protective antibodies that neutralized co-circulating H3N2 influenza viruses isolated over a 20-year period. This is the first study to show the effectiveness of H3N3 COBRA HA vaccines in a host with pre-existing immunity to influenza.
PMID: 30429350 DOI: 10.1128/JVI.00946-18
[h=1]Elicitation of protective antibodies against 20 years of future H3N2 co-ciruculating influenza virus variants in ferrets preimmune to historical H3N2 influenza viruses.[/h] Allen JD[SUP]1[/SUP], Jang H[SUP]1[/SUP], DiNapoli J[SUP]2[/SUP], Kleanthous H[SUP]2[/SUP], Ross TM[SUP]3,[/SUP][SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The vast majority of people already have pre-existing immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically na?ve animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 COBRA HA based vaccines boosted pre-existing antibodies induced by wild-type H1N1 virus infections. These H1 COBRA HA antigens induced antibodies with HAI activity against multiple antigenically different H1N1 viral variants. In this study, ferrets, preimmune to historical H3N2 viruses, were vaccinated with virus-like particle (VLP) vaccines expressing either an HA from a wild-type H3 influenza virus or a COBRA H3 HA antigen (T6, T7, T10, or T11). The elicited antisera had the ability to neutralize virus infection against a panel of viruses representing vaccine strains selected by the World Health Organization (WHO), or a set of viral variants that co-circulated during the same time period. Preimmune animals vaccinated with H3 COBRA T10 HA antigen elicited sera with higher HAI antibody titers than antisera elicited by VLP vaccines with wild-type HA VLPs in preimmune ferrets. However, while the T11 COBRA vaccine did not elicit HAI activity, the elicited antibodies did neutralize antigenically distinct H3N2 influenza viruses. Overall, H3 COBRA-based HA vaccines were able to neutralize both historical H3 and comtemporary, as well as future H3N2 viruses with higher titers than vaccines with wild-type H3 HA antigens. This is the first report demonstrating the effectiveness of a broadly reactive H3N3 vaccine in a preimmune ferret model.IMPORTANCE Following influenza virus exposure, the host generates neutralizing anti-hemagglutinin antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, co-circulating strains. The goal of next generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular those that persist over multiple influenza seasons, without requiring an update to the vaccine. To mimic the human condition, COBRA HA virus-like particle vaccines were tested in ferrets that were previously exposed to historical H3N2 influenza viruses. In this model, these vaccines elicited broadly protective antibodies that neutralized co-circulating H3N2 influenza viruses isolated over a 20-year period. This is the first study to show the effectiveness of H3N3 COBRA HA vaccines in a host with pre-existing immunity to influenza.
PMID: 30429350 DOI: 10.1128/JVI.00946-18