tetano
Editor, Senior Moderator
Front Microbiol. 2019 Jul 16;10:1630. doi: 10.3389/fmicb.2019.01630. eCollection 2019.
[h=1]Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses.[/h] Xie X[SUP]1[/SUP], Zhao C[SUP]1[/SUP], He Q[SUP]1[/SUP], Qiu T[SUP]1[/SUP], Yuan S[SUP]1[/SUP], Ding L[SUP]1[/SUP], Liu L[SUP]1[/SUP], Jiang L[SUP]1[/SUP], Wang J[SUP]1[/SUP], Zhang L[SUP]1[/SUP], Zhang C[SUP]2[/SUP], Wang X[SUP]2[/SUP], Zhou D[SUP]2[/SUP], Zhang X[SUP]1[/SUP], Xu J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Given that continuing antigenic shift and drift of influenza A viruses result in the escape from previous vaccine-induced immune protection, a universal influenza vaccine has been actively sought. However, there were very few vaccines capable of eliciting cross-group ant-influenza immunity. Here, we designed two novel composite immunogens containing highly conserved T-cell epitopes of six influenza A virus internal antigens, and expressed them in DNA, recombinant adenovirus-based (AdC68) and recombinant vaccinia vectors, respectively, to formulate three vaccine forms. The introduction of the two immunogens via a DNA priming and viral vectored vaccine boosting modality afforded cross-group protection from both PR8 and H7N9 influenza virus challenges in mice. Both respiratory residential and systemic T cells contributed to the protective efficacy. Intranasal but not intramuscular administration of AdC68 based vaccine was capable of raising both T cell subpopulations to confer a full protection from lethal PR8 and H7N9 challenges, and blocking the lymphatic egress of T cells during challenges attenuated the protection. Thus, by targeting highly conserved internal viral epitopes to efficiently generate both respiratory and systemic memory T cells, the sequential vaccination strategy reported here represented a new promising candidate for the development of T-cell based universal influenza vaccines.
[h=4]KEYWORDS:[/h] CD8+ T cell epitope; consensus sequence; cross-protection; lung residential T cells; universal influenza vaccine
PMID: 31379782 PMCID: PMC6647892 DOI: 10.3389/fmicb.2019.01630
[h=1]Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses.[/h] Xie X[SUP]1[/SUP], Zhao C[SUP]1[/SUP], He Q[SUP]1[/SUP], Qiu T[SUP]1[/SUP], Yuan S[SUP]1[/SUP], Ding L[SUP]1[/SUP], Liu L[SUP]1[/SUP], Jiang L[SUP]1[/SUP], Wang J[SUP]1[/SUP], Zhang L[SUP]1[/SUP], Zhang C[SUP]2[/SUP], Wang X[SUP]2[/SUP], Zhou D[SUP]2[/SUP], Zhang X[SUP]1[/SUP], Xu J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Given that continuing antigenic shift and drift of influenza A viruses result in the escape from previous vaccine-induced immune protection, a universal influenza vaccine has been actively sought. However, there were very few vaccines capable of eliciting cross-group ant-influenza immunity. Here, we designed two novel composite immunogens containing highly conserved T-cell epitopes of six influenza A virus internal antigens, and expressed them in DNA, recombinant adenovirus-based (AdC68) and recombinant vaccinia vectors, respectively, to formulate three vaccine forms. The introduction of the two immunogens via a DNA priming and viral vectored vaccine boosting modality afforded cross-group protection from both PR8 and H7N9 influenza virus challenges in mice. Both respiratory residential and systemic T cells contributed to the protective efficacy. Intranasal but not intramuscular administration of AdC68 based vaccine was capable of raising both T cell subpopulations to confer a full protection from lethal PR8 and H7N9 challenges, and blocking the lymphatic egress of T cells during challenges attenuated the protection. Thus, by targeting highly conserved internal viral epitopes to efficiently generate both respiratory and systemic memory T cells, the sequential vaccination strategy reported here represented a new promising candidate for the development of T-cell based universal influenza vaccines.
[h=4]KEYWORDS:[/h] CD8+ T cell epitope; consensus sequence; cross-protection; lung residential T cells; universal influenza vaccine
PMID: 31379782 PMCID: PMC6647892 DOI: 10.3389/fmicb.2019.01630