Non-Immunogenicity of Purified Hyaluronic Acid Preparations Tested by Passive Cutaneous Anaphylaxis

The immunogenicity of purified hyaluronic acid (HA) from human umbilical cord and rooster comb, and of some modified HA preparations, was studied in rabbits. HA preparations contained 0.28–0.57% of protein or peptides (Folin’s method). Rabbits received four intramuscular injections at 4-weekly intervals of the following potential immunogens, emulsified in complete Freund’s adjuvant: (1) human umbilical cord HA (HUC-HA), 500 μg/dose; (2) HUC-HA, precipitated with cetylpyridinium chloride (CPC), 500 μg/dose; (3) HUC-HA-ovalbumin conjugate, precipitated with CPC, 500 μg/dose, and (4) rooster comb HA at dose levels of 5, 50 and 500 μg. Rabbit sera were tested before, during, and after immunization for PCA reactive antibodies against HA in guinea pigs. 11 of 25 pre-immunization sera showed low titres of HA-cross-reactive antibodies. No formation of PCA reactive antibodies against any of the four HA preparations was observed during or after immunization.