A LIQUID CRYSTAL NANOSTRUCTURE, USED AS VACCINE PLATFORM, MODIFIES BIODISTRIBUTION OF VACCINE COMPONENTS

CONSTANZA MARIN; FERNANDA SÁNCHEZ-VALLECILLO; ANA CHIODETTI; SANTIAGO PALMA; MORON VG; DANIEL ALLEMANDI; MARÍA C PISTORESI- PALENCIA; BELKYS A. MALETTO

Buenos Aires

Congreso; LXV Reunión de la Sociedad Argentina de Inmunología. II Reunión Conjunta de Sociedades de Biociencias.; 2017

Sociedad Argentina de Inmunología

<!-- /* Font Definitions */ @font-face{font-family:Helvetica;panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1342208091 0 0 415 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073732485 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}p.MsoBodyText, li.MsoBodyText, div.MsoBodyText{mso-style-priority:1;mso-style-unhide:no;mso-style-qformat:yes;mso-style-link:"Texto independiente Car";margin-top:0cm;margin-right:5.25pt;margin-bottom:0cm;margin-left:2.0pt;margin-bottom:.0001pt;text-align:justify;mso-pagination:widow-orphan;mso-layout-grid-align:none;text-autospace:none;font-size:7.5pt;font-family:Helvetica;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-bidi-font-family:Helvetica;mso-fareast-language:EN-US;}span.TextoindependienteCar{mso-style-name:"Texto independiente Car";mso-style-priority:1;mso-style-unhide:no;mso-style-locked:yes;mso-style-link:"Texto independiente";mso-ansi-font-size:7.5pt;mso-bidi-font-size:7.5pt;font-family:Helvetica;mso-ascii-font-family:Helvetica;mso-hansi-font-family:Helvetica;mso-bidi-font-family:Helvetica;mso-ansi-language:ES-AR;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}@page WordSection1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->In the last years much effortin vaccinology has focused on the new formulation strategies for subunit vaccines.We formulated OVA (antigen) and CpG-ODN (TLR-9 agonist) with a nanostructureformed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16). We havepreviously shown that this nanovaccine (OVA/CpG-ODN/Coa- ASC16) elicited anadaptive immune response superior to those induced by an aqueous formulation(OVA/CpG-ODN). However, we still do not know exactly the mechanisms of actionof Coa-ASC16. Hence, the aim of this work was to test the impact of thisnanoformu- lation on biodistribution of vaccine components and early immuneresponse. Methods: mice were s.c. immunized with OVA/CpG-ODN orOVA/CpG-ODN/Coa-ASC16. OVA and CpG-ODN were labeled with near-infraredfluorescent dye, and both signals were measured with an Odyssey® CLx at severaltime points post immunization (pi). Cytokines/chemokines were evaluated inplasma by a multiplex as- say at 1.5h pi. Results are indicated asOVA/CpG-ODN vs OVA/ CpG-ODN/Coa-ASC16. Liver: OVA signal was 1.2 x 107 vs 0.6 x 107(p<0.01), 4.3 x 107 vs 1.0 x 107 (p<0.001) and 2.0 x 107 vs 0.8 x 107 (p<0.01) at 20 min, 2 and4h pi. No signal was observed in spleen and kidney in any of groups. Injectionsite: OVA signal was 1.6 x 106 vs 6.9 x 106 (p<0.001) and 0.05 x 106 vs 2.45 x 106 (p<0.05) at 0.3 and 5 days pi; for CpG-ODN there was no significantdifferences between both groups at any time. Lymph node: OVA signal was 1.8 x105 vs 0.3 x 105 (p<0.01),0.5 x 105 vs 4.5 x 105 (p<0.001)and 0.1 x 105 vs 2.8 x 105 (p<0.01)at 20 min, 2 and 24h pi; in contrast CpG- ODN signal was similar between twogroups at 20 min and 2h pi. In addition, soluble vaccine elicited higheramounts of systemic TNF-α and MCP-1 than nanovaccineimmunization (p<0.05). Conclusions: Coa-ASC16 retains antigen at theinjection site but not CpG-ODN, and promotes co-delivery of both molecules tolymph node without comitant induction of systemic inflammation.