Selection of a muramyl peptide based on its lack of activation of nuclear factor‐κB as a potential adjuvant for AIDS vaccines

• Published in: Clinical and experimental immunology Vol. 90; no. 2; pp. 188 - 193
• Main Authors: SCHRECK, R., BEVEC, D., DUKOR, P., BAEUERLE, P. A., CHEDID, L., BAHR, G. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.1992; Blackwell
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - chemistry; Acetylmuramyl-Alanyl-Isoglutamine - immunology; Acquired Immunodeficiency Syndrome - therapy; adjuvants; Adjuvants, Immunologic; AIDS; AIDS/HIV; Animals; Antioxidants - pharmacology; Base Sequence; Biological and medical sciences; Cell Line; Fundamental and applied biological sciences. Psychology; Gene Expression; Humans; In Vitro Techniques; Interleukin-8 - genetics; Mice; Microbiology; Molecular Sequence Data; muramyl peptides; NF-kappa B - metabolism; NF‐κB; Oligodeoxyribonucleotides - chemistry; Reactive Oxygen Species - metabolism; Structure-Activity Relationship; vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Virology; Human; HIV-1 virus; Retroviridae; Vaccine; Virus; Immunomodulator; Immunostimulant agent; Cell line; Immunological adjuvant; T-Lymphocyte; Lentivirinae; Replication; Human immunodeficiency virus; Infected cell; Transcription factor
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1992.tb07926.x

SUMMARY Activation of the cellular transcription factor nuclear factor‐κB (NF‐κB) by cytokines and other immunostimulants has been tightly linked with enhanced replication of human immunodeficiency virus‐type 1 (HIV‐1) in infected cells. Various immunomodulators are currently being examined in animal and human trials for their suitability as adjuvants in potential vaccines against acquired immunodeficiency syndrome (AIDS). It may prove to be beneficial to select adjuvants that do not induce NF‐κB activation and particularly if the vaccines are to be aimed at seropositive individuals. We have examined a battery of synthetic immunostimulants of the muramyl peptide family for their ability to activate NF‐κB in human and mouse cell lines. In this report, we demonstrate selective activation of NF‐κB in different cell lines and by different muramyl peptides possessing immunostimulatory activities. The mechanism of such activation is apparently via production of reactive oxygen intermediates (RO1) since pretreatment of cells with antioxidants blocked subsequent activation of NF‐κB. However, among all the molecules tested only one lipophilic, non‐pyrogenic adjuvant active muramyl peptide showed a complete lack of NF‐κB activation in all cell lines tested. This molecule could well become the adjuvant of choice in future AIDS vaccines.