Comparative study of the effects of peptidoglycan monomer and structurally related adamantyltripeptides on humoral immune response to ovalbumin in the mouse

• Published in: Vaccine 2000-01, Vol.18 (13), p.1236-1243
• Main Authors: TOMASIC, J, HANZL-DUJMOVIC, I, SPOLJAR, B, VRANESIC, B, SANTAK, M, JOVICIC, A
• Format: Article
• Language: English
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - administration & dosage; Acetylmuramyl-Alanyl-Isoglutamine - analogs & derivatives; Acetylmuramyl-Alanyl-Isoglutamine - immunology; Adamantane - administration & dosage; Adamantane - analogs & derivatives; Adamantane - immunology; Adamantane - pharmacology; Adamantyltripeptides; Adjuvants; Adjuvants, Immunologic - administration & dosage; Animals; Applied microbiology; Biological and medical sciences; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Immunoglobulin A - biosynthesis; Immunoglobulin G - biosynthesis; Immunoglobulin G - classification; Immunoglobulin M - biosynthesis; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Microbiology; Oligopeptides - administration & dosage; Oligopeptides - immunology; Oligopeptides - pharmacology; ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - immunology; Peptidoglycan; Peptidoglycan monomer; peptidoglycans; Stereoisomerism; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(99)00382-5

Peptidoglycan monomer, GlcNAc–MurNAc– l–Ala– d- isoGln– mesoDAP( ωNH 2)- d–Ala– d-Ala (PGM) originating from Brevibacterium divaricatum and synthetic adamantyltripeptides, diastereoisomers of d, l-(adamant-2-yl)–Gly– l-Ala– d- isoGln (AdTP1 and AdTP2) exhibit immunomodulating activity. An experimental model in the mouse has been established with suboptimal amounts of ovalbumin (OVA) as the immunogen, and parallel testing of adjuvant activity of these three immunomodulators was carried out in Balb/c, C57Bl6 or CBA mice. Tested compounds (100 or 200 μg/mouse) mixed with OVA in saline (50 μg/mouse) were administered s.c. Anti-OVA was assayed by ELISA in the sera of mice taken 7 days after the boosters (given on days 14 and 28). The treatment with PGM and one of the diastereoisomers, AdTP2, resulted in significantly higher increase in anti-OVA IgG levels (stimulation index up to 46) with respect to controls and groups treated with AdTP1. The effect of AdTP2 treatment was comparable to that of PGM in most experiments after the first booster, but after the second booster PGM exhibited markedly better effect. PGM and AdTP2 also induced markedly higher levels of IgG1 and IgG2 anti-OVA subclasses than detected in controls and AdTP1 treated mice, indicating that these two immunomodulators might upregulate both Th1-like and Th2-like immune responses.