tetano
Editor, Senior Moderator
Vaccine. 2015 Dec 23. pii: S0264-410X(15)01836-8. doi: 10.1016/j.vaccine.2015.12.039. [Epub ahead of print]
[h=1]Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell-dependent, cross-clade protection against H5N1 influenza virus in mice.[/h] Zhang J[SUP]1[/SUP], Zhang Z[SUP]1[/SUP], Fan HY[SUP]1[/SUP], Zhang J[SUP]2[/SUP], Zhang J[SUP]1[/SUP], Huang JN[SUP]2[/SUP], Ye Y[SUP]1[/SUP], Liao M[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] H5N1, highly pathogenic avian influenza poses, a threat to animal and human health. Rapid changes in H5N1 viruses require periodic reformulation of the conventional strain-matched vaccines, thus emphasizing the need for a broadly protective influenza vaccine. Here, we constructed BV-Dual-3M2e-LTB, a recombinant baculovirus based on baculovirus display and BacMam technology. BV-Dual-3M2e-LTB harbors a gene cassette expressing three tandem copies of the highly conserved extracellular domain of influenza M2 protein (M2e) and the mucosal adjuvant, LTB. We showed that BV-Dual-3M2e-LTB displayed the target protein (M2e/LTB) on the baculoviral surface and expressed it in transduced mammalian cells. BV-Dual-3M2e-LTB, when delivered nasally in mice, was highly immunogenic and induced superior levels of anti-M2e IgA than the non-adjuvanted baculovirus (BV-Dual-3M2e). Importantly, after challenge with different H5N1 clades (clade 0, 2.3.2.1, 2.3.4 and 4), mice inoculated with BV-Dual-3M2e-LTB displayed improved survival and decreased lung virus shedding compared with mice inoculated with BV-Dual-3M2e. The enhanced protection from BV-Dual-3M2e-LTB is mediated by T cell immunity and is primarily based on CD8[SUP]+[/SUP] T cells, while mucosal antibodies alone were insufficient for protection from lethal H5N1 challenge. These results suggest that BV-Dual-3M2e-LTB has potential to protect against a broad range of H5N1 strains thereby providing a novel direction for developing broadly protective vaccines based on cellular immunity.
Copyright ? 2015. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Baculovirus; H5N1; Influenza; LTB; M2e
PMID: 26724200 [PubMed - as supplied by publisher]
[h=1]Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell-dependent, cross-clade protection against H5N1 influenza virus in mice.[/h] Zhang J[SUP]1[/SUP], Zhang Z[SUP]1[/SUP], Fan HY[SUP]1[/SUP], Zhang J[SUP]2[/SUP], Zhang J[SUP]1[/SUP], Huang JN[SUP]2[/SUP], Ye Y[SUP]1[/SUP], Liao M[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] H5N1, highly pathogenic avian influenza poses, a threat to animal and human health. Rapid changes in H5N1 viruses require periodic reformulation of the conventional strain-matched vaccines, thus emphasizing the need for a broadly protective influenza vaccine. Here, we constructed BV-Dual-3M2e-LTB, a recombinant baculovirus based on baculovirus display and BacMam technology. BV-Dual-3M2e-LTB harbors a gene cassette expressing three tandem copies of the highly conserved extracellular domain of influenza M2 protein (M2e) and the mucosal adjuvant, LTB. We showed that BV-Dual-3M2e-LTB displayed the target protein (M2e/LTB) on the baculoviral surface and expressed it in transduced mammalian cells. BV-Dual-3M2e-LTB, when delivered nasally in mice, was highly immunogenic and induced superior levels of anti-M2e IgA than the non-adjuvanted baculovirus (BV-Dual-3M2e). Importantly, after challenge with different H5N1 clades (clade 0, 2.3.2.1, 2.3.4 and 4), mice inoculated with BV-Dual-3M2e-LTB displayed improved survival and decreased lung virus shedding compared with mice inoculated with BV-Dual-3M2e. The enhanced protection from BV-Dual-3M2e-LTB is mediated by T cell immunity and is primarily based on CD8[SUP]+[/SUP] T cells, while mucosal antibodies alone were insufficient for protection from lethal H5N1 challenge. These results suggest that BV-Dual-3M2e-LTB has potential to protect against a broad range of H5N1 strains thereby providing a novel direction for developing broadly protective vaccines based on cellular immunity.
Copyright ? 2015. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Baculovirus; H5N1; Influenza; LTB; M2e
PMID: 26724200 [PubMed - as supplied by publisher]