tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2018 Jul 31. pii: 201805713. doi: 10.1073/pnas.1805713115. [Epub ahead of print]
[h=1]Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice.[/h] Deng L[SUP]1[/SUP], Chang TZ[SUP]2[/SUP], Wang Y[SUP]1[/SUP], Li S[SUP]2[/SUP], Wang S[SUP]3[/SUP], Matsuyama S[SUP]1[/SUP], Yu G[SUP]4[/SUP], Compans RW[SUP]3[/SUP], Li JD[SUP]1[/SUP], Prausnitz MR[SUP]2[/SUP], Champion JA[SUP]2[/SUP], Wang BZ[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza is a persistent threat to public health. Here we report that double-layered peptide nanoparticles induced robust specific immunity and protected mice against heterosubtypic influenza A virus challenges. We fabricated the nanoparticles by desolvating a composite peptide of tandem copies of nucleoprotein epitopes into nanoparticles as cores and cross-linking another composite peptide of four tandem copies of influenza matrix protein 2 ectodomain epitopes to the core surfaces as a coating. Delivering the nanoparticles via dissolvable microneedle patch-based skin vaccination further enhanced the induced immunity. These peptide-only, layered nanoparticles demonstrated a strong antigen depot effect and migrated into spleens and draining (inguinal) lymph nodes for an extended period compared with soluble antigens. This increased antigen-presentation time correlated with the stronger immune responses in the nanoparticle-immunized group. The protection conferred by nanoparticle immunization was transferable by passive immune serum transfusion and depended partially on a functional IgG receptor FcγRIV. Using a conditional cell depletion, we found that CD8[SUP]+[/SUP] T cells were involved in the protection. The immunological potency and stability of the layered peptide nanoparticles indicate applications for other peptide-based vaccines and peptide drug delivery.
[h=4]KEYWORDS:[/h] epitope; influenza A virus; microneedle; nanoparticle; universal influenza vaccine
PMID: 30065113 DOI: 10.1073/pnas.1805713115
[h=1]Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice.[/h] Deng L[SUP]1[/SUP], Chang TZ[SUP]2[/SUP], Wang Y[SUP]1[/SUP], Li S[SUP]2[/SUP], Wang S[SUP]3[/SUP], Matsuyama S[SUP]1[/SUP], Yu G[SUP]4[/SUP], Compans RW[SUP]3[/SUP], Li JD[SUP]1[/SUP], Prausnitz MR[SUP]2[/SUP], Champion JA[SUP]2[/SUP], Wang BZ[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza is a persistent threat to public health. Here we report that double-layered peptide nanoparticles induced robust specific immunity and protected mice against heterosubtypic influenza A virus challenges. We fabricated the nanoparticles by desolvating a composite peptide of tandem copies of nucleoprotein epitopes into nanoparticles as cores and cross-linking another composite peptide of four tandem copies of influenza matrix protein 2 ectodomain epitopes to the core surfaces as a coating. Delivering the nanoparticles via dissolvable microneedle patch-based skin vaccination further enhanced the induced immunity. These peptide-only, layered nanoparticles demonstrated a strong antigen depot effect and migrated into spleens and draining (inguinal) lymph nodes for an extended period compared with soluble antigens. This increased antigen-presentation time correlated with the stronger immune responses in the nanoparticle-immunized group. The protection conferred by nanoparticle immunization was transferable by passive immune serum transfusion and depended partially on a functional IgG receptor FcγRIV. Using a conditional cell depletion, we found that CD8[SUP]+[/SUP] T cells were involved in the protection. The immunological potency and stability of the layered peptide nanoparticles indicate applications for other peptide-based vaccines and peptide drug delivery.
[h=4]KEYWORDS:[/h] epitope; influenza A virus; microneedle; nanoparticle; universal influenza vaccine
PMID: 30065113 DOI: 10.1073/pnas.1805713115