All-trans retinoic acid potentiates the antibody response in mice to a lipopeptide antigen adjuvanted with liposomal lipid A.
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.
Watson
Douglas S
DS
Departments of Bioengineering and Therapeutic Sciences and Pharmaceutical Chemistry, University of California, San Francisco, 94143-0912, USA.
Huang
Zhaohua
Z
Szoka
Francis C
FC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D004357:Drug Synergism; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage* / Q000276:immunology; D055666:Lipopeptides / Q000276:immunology*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015700:HIV Envelope Protein gp41; D008050:Lipid A; D055666:Lipopeptides; D008081:Liposomes; D014212:Tretinoin