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All ‐trans retinoic acid potentiates the antibody response in mice to a lipopeptide antigen adjuvanted with liposomal lipid A
Author(s) -
Watson Douglas S,
Huang Zhaohua,
Szoka Francis C
Publication year - 2009
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.48
Subject(s) - lipopeptide , adjuvant , immunogen , liposome , pharmacology , antigen , agonist , chemistry , antibody , receptor , immunology , biology , biochemistry , monoclonal antibody , genetics , bacteria
Retinoic acid (RA), the bioactive metabolite of retinol, is essential for robust humoral immunity in animals and humans. Recent interest in RA as a vaccine adjuvant has been encouraged by reports showing cooperative enhancement of antibody responses to tetanus toxin in rodents by all‐ trans RA (ATRA) and a Toll‐like receptor‐3 agonist. We hypothesized that RA would augment the antibody response to a co‐delivered lipopeptide immunogen derived from the membrane proximal region (MPR) of HIV‐1 gp41. The MPR is weakly immunogenic and could benefit from potent new humoral adjuvants. When co‐formulated in liposomes and administered to BALB/C mice, ATRA alone did not elicit serum anti‐peptide antibodies to an MPR‐derived lipopeptide. However, addition of ATRA, but not 13 ‐cis RA, to a liposomal formulation containing the Toll‐like receptor‐4 agonist monophosphoryl lipid A resulted in a fourfold enhancement of serum anti‐peptide IgG titers as compared with a formulation containing lipid A alone ( P =0.00039). The difference did not arise from biophysical changes in the liposome formulation, including vesicle size, vesicle charge and liposome association of antigen. Thus, ATRA warrants further study as a vaccine adjuvant.