tetano
Editor, Senior Moderator
NPJ Vaccines. 2019 May 15;4:17. doi: 10.1038/s41541-019-0111-y. eCollection 2019.
[h=1]Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages.[/h] Makarkov AI[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Golizeh M[SUP]2[/SUP], Ruiz-Lancheros E[SUP]2[/SUP], Gopal AA[SUP]4,[/SUP][SUP]5[/SUP], Costas-Cancelas IN[SUP]6[/SUP], Chierzi S[SUP]7[/SUP], Pillet S[SUP]2,[/SUP][SUP]8[/SUP], Charland N[SUP]8[/SUP], Landry N[SUP]8[/SUP], Rouiller I[SUP]6,[/SUP][SUP]9[/SUP], Wiseman PW[SUP]4,[/SUP][SUP]10[/SUP], Ndao M[SUP]2,[/SUP][SUP]11[/SUP], Ward BJ[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance, and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4[SUP]+[/SUP] T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. Compared to exposure to soluble HA, pulsing with VLPs resulted in ~3-fold greater intracellular accumulation of HA at 15 min that was driven by clathrin-mediated and clathrin-independent endocytosis as well as macropinocytosis/phagocytosis. At 45 min, soluble HA had largely disappeared suggesting its handling primarily by high-degradative endosomal pathways. Although the overall fluorescence intensity/cell had declined 25% at 45 min after H1-VLP exposure, the endosomal distribution pattern and degree of aggregation suggested that HA delivered by VLP had entered both high-degradative late and low-degradative static early and/or recycling endosomal pathways. At 45 min in the cells pulsed with VLPs, HA was strongly co-localized with Rab5, Rab7, Rab11, MHC II, and MHC I. High-resolution tandem mass spectrometry identified 115 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. These data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing, and cross-presentation. These observations may help to explain the broad and cross-reactive immune responses generated by these vaccines.
[h=4]KEYWORDS:[/h] Cellular immunity; Influenza virus; Recombinant vaccine; Vaccines
PMID: 31123605 PMCID: PMC6520342 DOI: 10.1038/s41541-019-0111-y
[h=1]Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages.[/h] Makarkov AI[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Golizeh M[SUP]2[/SUP], Ruiz-Lancheros E[SUP]2[/SUP], Gopal AA[SUP]4,[/SUP][SUP]5[/SUP], Costas-Cancelas IN[SUP]6[/SUP], Chierzi S[SUP]7[/SUP], Pillet S[SUP]2,[/SUP][SUP]8[/SUP], Charland N[SUP]8[/SUP], Landry N[SUP]8[/SUP], Rouiller I[SUP]6,[/SUP][SUP]9[/SUP], Wiseman PW[SUP]4,[/SUP][SUP]10[/SUP], Ndao M[SUP]2,[/SUP][SUP]11[/SUP], Ward BJ[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance, and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4[SUP]+[/SUP] T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. Compared to exposure to soluble HA, pulsing with VLPs resulted in ~3-fold greater intracellular accumulation of HA at 15 min that was driven by clathrin-mediated and clathrin-independent endocytosis as well as macropinocytosis/phagocytosis. At 45 min, soluble HA had largely disappeared suggesting its handling primarily by high-degradative endosomal pathways. Although the overall fluorescence intensity/cell had declined 25% at 45 min after H1-VLP exposure, the endosomal distribution pattern and degree of aggregation suggested that HA delivered by VLP had entered both high-degradative late and low-degradative static early and/or recycling endosomal pathways. At 45 min in the cells pulsed with VLPs, HA was strongly co-localized with Rab5, Rab7, Rab11, MHC II, and MHC I. High-resolution tandem mass spectrometry identified 115 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. These data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing, and cross-presentation. These observations may help to explain the broad and cross-reactive immune responses generated by these vaccines.
[h=4]KEYWORDS:[/h] Cellular immunity; Influenza virus; Recombinant vaccine; Vaccines
PMID: 31123605 PMCID: PMC6520342 DOI: 10.1038/s41541-019-0111-y