Impact of antigen-adjuvant associations on antigen uptake and antigen-specific humoral immunity in mice following intramuscular injection

Biomed Pharmacother. 2019 Oct:118:109373. doi: 10.1016/j.biopha.2019.109373. Epub 2019 Aug 29.

Abstract

The effect of antigen-adjuvant associations on antigen uptake and antigen-specific humoral immunity is studied in detail. After formulation with a squalene-based double emulsion (referred to as PELC), the protein ovalbumin (OVA) was intramuscularly injected in mice, in either a separation (OVA-PELCSE), a surface attachment (OVA-PELCSA) or an encapsulation (OVA-PELCEN) manner. As an antigen delivery system, a significant increase of OVA-loaded cells migrating into draining lymph nodes (LNs) was detected in the PELC-formulated OVA groups, attachment and encapsulation as well. Additionally, OVA-PELCEN allowed the mice to induce a delayed but long-lasting OVA-specific antibodies production compared to OVA-PELCSA. In the extreme case where no antigen-adjuvant association at all (i.e., OVA-PELCSE), we found that even with the presence of PELC at the contralateral limb, an elevated level of OVA uptake was detected in ipsilateral draining CD11c+ LN cells, which subsequently augmented the production of OVA-specific IgG antibodies during early vaccination. The mouse study allows us to find out the optimal vaccine formulation and deepens our understandings on how antigen-adjuvant associations can govern the cellular uptake and transportation of protein antigen into the draining LNs and prolong antigen-specific humoral immunity, even if the antigen and the adjuvant are given separately.

Keywords: Antigen-adjuvant association; Double emulsion; Squalene; Vaccine adjuvant.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigen-Presenting Cells / metabolism
  • Antigens / immunology*
  • CD11c Antigen / metabolism
  • Cell Movement / drug effects
  • Emulsions / chemistry
  • Female
  • Immunity, Humoral* / drug effects
  • Injections, Intramuscular
  • Lymph Nodes / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Antigens
  • CD11c Antigen
  • Emulsions