Class-B CpG-ODN formulated with a nanostructure induces type I interferons-dependent and CD4+ T cell-independent CD8+ T-cell response against unconjugated protein antigen

ANA CHIODETTI; FERNANDA SÁNCHEZ-VALLECILLO; JOSEPH DOLINA; MARÍA INÉS CRESPO; CONSTANZA MARIN; STEPHEN SCHOENBERGER; DANIEL ALLEMANDI; SANTIAGO PALMA; MARÍA C PISTORESI- PALENCIA; GABRIEL MORON; BELKYS A. MALETTO

Frontiers in Immunology

Frontiers

Lugar: Lausanne; Año: 2018

There is a need for new vaccine adjuvant strategiesthat offer both vigorous antibody and T-cell mediated protection to combat difficult intracellularpathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotidecontaining unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 orcoagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previousresults demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16(OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellularresponses without toxic systemic effects. These responses were superior tothose induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In thisstudy, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicitCD8+ T-cell responseand some of the underlying cellular and molecular mechanisms involved in adaptiveresponse. We also analyzed whether this adjuvant strategy allows a switch from animmunization scheme of three-doses to one of single-dose. Our results demonstrated thatvaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoralresponse and importantly-high quality CD8+ T cell immunity with a single-dose immunization.Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells.The CD8+ T-cell responseinduced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons andindependent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellularpathogen. Furthermore, the cellular and humoral responses elicited by thenanostructured formulation were IL-6-independent. This system provides a simpleand inexpensive adjuvant strategy with great potential for future rationallydesigned vaccines.<!-- /* 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 -1073697537 9 0 511 0;}@font-face{font-family:"Times New Roman (Cuerpo en alfa";panose-1:2 2 6 3 5 4 5 2 3 4;mso-font-alt:"Times New Roman";mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536859921 -1073711039 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:Helvetica;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman (Cuerpo en alfa";mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Helvetica;mso-ascii-font-family:Helvetica;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Helvetica;mso-bidi-font-family:"Times New Roman (Cuerpo en alfa";mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}@page WordSection1{size:595.0pt 842.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->