Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model.

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Otero M, Calarota SA, Felber B, Laddy D, Pavlakis G, Boyer JD, Weiner DB

Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model.

Vaccine. 2004 Apr 16;22(13-14):1782-90.

PubMed ID

15068862 [ View in PubMed

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Abstract

DNA vaccines have been effective at generating useful immune responses in many animal species. However, it is clearly desirable to increase their potency. The identification of adjuvants that increase their cell-mediated immune (CMI) response is therefore an important goal. Resiquimod is an imiquimod analog proven to activate dendritic cells through TLR-7. The adjuvant capacity of resiquimod has not, to our knowledge, been studied in the context of genetic immunization. Here, we studied resiquimod as an adjuvant for plasmid vaccine therapy by intra-muscular immunization of BALB/c mice with HIV-1 gag DNA vaccine without and with several concentrations of resiquimod (ranging from 5-100nM). We observed that resiquimod moderately enhanced IFN-gamma production as measured by a peptide-based ELISPOT assay compared to that obtained in mice immunized with DNA gag only. Antigen-specific T-cell proliferation studies showed a several-fold increase in the stimulation index in mice immunized with DNA gag +50 nM of resiquimod as compared to mice receiving DNA gag alone. Antibody titer also increased, while the antibody isotyping data showed a strong Th1 biased type response. Analysis of cytokine production in serum samples demonstrated a stronger Th1 cytokine bias in the presence of resiquimod. Furthermore, relevant increase in IL-4 production, as measured by ELISPOT assay, was not observed. Our results show that resiquimod can have modest adjuvant activity, in a DNA formulation, driving the immune system towards a cell-mediated immune response. Additional studies involving this adjuvant for DNA vaccines are underway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Imiquimod	Toll-like receptor 7	Protein	Humans	Yes	Agonist	Details