Cutaneous CpG adjuvant conditioning to enhance vaccine responses

• Published in: Vaccine 2022-03, Vol.40 (10), p.1385-1389
• Main Authors: Carlow, Douglas A., Lai, Jacqueline C.Y., Kollmann, Tobias R., Sadarangani, Manish, Dutz, Jan P.
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic; Animals; Antigens; CD8 antigen; CD8+ T cells; Cloning; Conditioning; CpG; CpG islands; Epigenetics; Experiments; Immunoglobulin G; Immunological memory; Innate immunity; Intradermal immunization; Lymphatic system; Lymphocytes; Lymphocytes T; Memory cells; Mice; Mice, Inbred C57BL; Oligodeoxyribonucleotides; Ovalbumin; Pathogens; Skin; Vaccination; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.12.060

[Display omitted] •Separating adjuvant timing and location from antigen exposure.•Prior intradermal adjuvant benefits subcutaneous vaccination outcome.•Toward single-dose vaccination. Adjuvant activity of the Toll receptor 9 agonist CpG 1826 was compared when given subcutaneously (s.c.) together with ovalbumin (s.c.[CpG + Ova]), or when given by either s.c. or intradermally (i.d.) routes two days prior to s.c. ovalbumin. Frequencies of CD8 + effector (TEFF) and central memory (TCM) T cells along with total IgG, IgG2c, and IgG1 titres were measured to ascertain how timing and location of CpG conditioning influenced vaccination outcome. Prior treatment with CpG enhanced TEFF, TCM, as well as total IgG responses. TEFF and TCM responses were greatest when CpG was given intradermally and prior to s.c. ovalbumin, conditions that eliminated the fraction of TCM ‘non-responders’ observed after s.c.[CpG + Ova] vaccination. IgG responses were polarized toward IgG2c after early s.c. CpG but toward IgG1 after early i.d. CpG. Separating CpG adjuvant and antigen application in time and space can improve vaccination outcome.