Formulation of aluminum hydroxide adjuvant with TLR agonists poly(I:C) and CpG enhances the magnitude and avidity of the humoral immune response

Fangjia Lu, Yung Yi C. Mosley, Brooke Carmichael, Devonte D. Brown, Harm HogenEsch

Research output: Contribution to journalArticle

Abstract

Subunit vaccines generally require adjuvants to achieve optimal immune responses. Toll-like receptor (TLR) agonists are promising immune potentiators, but rapid diffusion from the injection site reduces their local effective concentration and may cause systemic reactions. In this study, we investigated the potential of aluminum hydroxide adjuvant (AH) to adsorb the TLR3 agonist poly(I:C) and TLR9 agonist CpG and compared the effect of the combination adjuvant on the immune response with either the TLR agonists or AH alone in mice. Poly(I:C) and CpG readily adsorbed onto AH and this combination adjuvant induced a stronger IgG1 and IgG2a immune response with a significant increase of antibody avidity. The combination adjuvant enhanced antigen uptake and activation of dendritic cells in vitro. It induced an inflammatory response at the injection site similar to AH but without eosinophils which are typically observed with AH. A distinctive antigen-containing monocyte/macrophage population with an intermediate level of CD11c expression was identified in the draining lymph nodes after immunization with TLR agonists and the combination adjuvant. Injection of the combination adjuvant did not induce an increase of TNFα and CXCL10 in serum in contrast to the injection of soluble TLR agonists. These results indicate that this combination adjuvant is a promising formulation to solve some of the unmet needs of current vaccines.

Original languageEnglish (US)
JournalVaccine
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Aluminum Hydroxide
polyinosinic-polycytidylic acid
aluminum hydroxide
Toll-Like Receptors
Humoral Immunity
humoral immunity
agonists
adjuvants
Injections
Antigens
Subunit Vaccines
Antibody Affinity
Eosinophils
injection site
Dendritic Cells
immune response
Monocytes
Immunization
Vaccines
Immunoglobulin G

Keywords

  • Adjuvants
  • Cytokines
  • Inflammation
  • Toll-like receptors
  • Vaccines

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Formulation of aluminum hydroxide adjuvant with TLR agonists poly(I:C) and CpG enhances the magnitude and avidity of the humoral immune response. / Lu, Fangjia; Mosley, Yung Yi C.; Carmichael, Brooke; Brown, Devonte D.; HogenEsch, Harm.

In: Vaccine, 01.01.2019.

Research output: Contribution to journalArticle

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