Induction of immune response to protein antigens by subcutaneous co-injection with water-miscible vitamin A derivatives

Subunit vaccines require potent adjuvants to induce effective immunity. Currently, most known adjuvants have not been approved for human and veterinary use, mainly because of adverse effects resulting from local injections. A material with adjuvant properties proven to be safe for the host would be of importance, particularly if it had a constructive physiological role. A possible candidate is vitamin A and its analogues. The objectives herein were to re-evaluate adjuvant properties of vitamin A by employing water-miscible vitamin A (WMVA) derivatives (retinol palmitate and retinoic acid), and to determine their ability to induce effective immune responses to protein antigens. Injection of WMVA in aqueous solution prevented adverse effects of local injection, hypervitaminosis and oil depot damage. Other results show that WMVA derivatives behave as extrinsic adjuvants, and increase immune responses to protein antigens without causing hypervitaminosis or significant elevation of liver vitamin A. Primary immune responses were of short duration, but were increased and maintained by booster immunizations. The responses induced by WMVA derivatives were of similar magnitude to those induced by water soluble murmyl-dipeptide and Salmonella typhimurium mitogen. Hence, WMVA derivatives have potential as both efficient and safe adjuvants.