Immunogen

An immunogen is any substance that generates B-cell (humoral/antibody) and/or T-cell (cellular) adaptive immune responses upon exposure to a host organism.^[1]^[2] Immunogens that generate antibodies are called antigens ("antibody-generating").^[2] Immunogens that generate antibodies are directly bound by host antibodies and lead to the selective expansion of antigen-specific B-cells. Immunogens that generate T-cells are indirectly bound by host T-cells after processing and presentation by host antigen-presenting cells.

An immunogen can be defined as a complete antigen which is composed of the macromolecular carrier and epitopes (determinants) that can induce immune response.

An explicit example is a hapten. Haptens are low-molecular-weight compounds that may be bound by antibodies, but cannot elicit an immune response. Consequently, the haptens themselves are nonimmunogenic and they cannot evoke an immune response until they bind with a larger carrier immunogenic molecule. The hapten-carrier complex, unlike free hapten, can act as an immunogen and can induce an immune response.^[3]

Until 1959, the terms immunogen and antigen were not distinguished.^[4]

Used carrier proteins

Keyhole limpet hemocyanin

It is copper-containing respiratory protein, isolated from keyhole limpets (Megathura crenulata). Because of its evolutionary distance from mammals, high molecular weight and complex structure it is usually immunogenic in vertebrate animals.^[5]

Concholepas concholepas hemocyanin

(also blue carrier immunogenic orotein) It is alternative to KLH isolated from Concholepas concholepas. It has the similar immunogenic properties as KLH but better solubility and therefore better flexibility.^[6]

Bovine serum albumin

It is from the blood sera of cows and has similarly immunogenic properties as KLH or CCH. The cationized form of BSA (cBSA) is highly positively charged protein with significantly increased immunogenicity. This change possesses a greater number of possible conjugated antigens to the protein.^[7]

Ovalbumin

Also known as egg albumin, OVA is the main protein (60-75%) found in hen egg white. OVA is soluble in dimethyl sulfoxide (DMSO), which enables the conjugation of haptens that are not soluble in aqueous buffers. The immune response can be enhanced using an adjuvant injected together with the immunogen.^[8]

Immunological adjuvants

An adjuvant (from Latin adiuvare – to help) is any substance, distinct from antigen, which enhances immune response by various mechanisms: recruiting of professional antigen-presenting cells (APCs) to the site of antigen exposure; increasing the delivery of antigens by delayed/slow release (depot generation); immunomodulation by cytokine production (selection of Th1 or Th2 response); inducing T-cell response (prolonged exposure of peptide-MHC complexes [signal 1] and stimulation of expression of T-cell-activating co-stimulators [signal 2] on the APCs' surface) and targeting (e. g. carbohydrate adjuvants which target lectin receptors on APCs). Adjuvants have been used as additives to improve vaccine efficiency since the 1920s. Generally, administration of adjuvants is used both in experimental immunology and in clinical settings to ensure a high quality/quantity memory-enhanced antibody response, where antigens must be prepared and delivered in a fashion that maximizes production of a specific immune response. Among commonly used adjuvants are complete and incomplete Freund's adjuvant and solutions of aluminum hydroxide or aluminum phosphate.^[9]^[10]

References

^ "im·mu·no·gen", Merriam-Webster Collegiate Dictionary (11th ed.), Springfield, Massachusetts, USA: Merriam-Webster, Inc., 2003, a substance that produces an immune response
^ ^a ^b "Immunogen". immunopaedia.org.za. 4 March 2015. Archived from the original on 2021-10-21. Retrieved 2021-10-21. A substance capable of eliciting a immune response. All immunogens are antigens, but some antigen are not immunogens (e.g. haptens)
^ Abbas A.K.; Lichtman A.H.; Pillai S. (2012). Cellular and Molecular Immunology. 7th edition. Elsevier, Ed. Gruliow R. pp. 101–103, 483.
^ Medical Dictionary, Merriam-Webster. "Immunogen". Archived from the original on 2014-01-01. Retrieved 2013-12-31.
^ Harris J.R.; Markl J. (1999). "Keyhole limpet hemocyanin (KHL): a biomedical review". Micron. 30 (6): 597–623. doi:10.1016/s0968-4328(99)00036-0. PMID 10544506.
^ Arancibia S.; Del Campo M.; Nova E.; Salazar F.; Becker M.I. (2012). "Enhanced structural stability of Concholepashemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects". Eur J Immunol. 42 (3): 688–99. doi:10.1002/eji.201142011. hdl:10533/126832. PMID 22144228. S2CID 205788372.
^ Chen J.S.; Chen A.; Chang L.Ch.; Chang W.S.W.; Lee H.S.; Lin S.H.; Lin Y.F. (2004). "Mouse model of membranous nephopathy induced by cationic bovine serum albumin: antigen dose response relation and strain differences". Nephrol Dial Transplant. 19 (11): 2721–2728. doi:10.1093/ndt/gfh419. PMID 15385633.
^ De Silva B.S.; Egodage K.L.; Wilson G.S. (1999). "Purified protein derivate (PPD) as an immunogen carrier elicits high antigen specificity to haptens". Bioconjug Chem. 10 (3): 496–501. doi:10.1021/bc9800724. PMID 10346883.
^ Abbas A.K.; Lichtman A.H.; Pillai S. (2012). Cellular and Molecular Immunology. Elsevier. p. 85.
^ Cox J.C.; Coulter A.R. (1997). "Adjuvants –a classification and review of their modes of action". Vaccine. 15 (3): 248–256. doi:10.1016/s0264-410x(96)00183-1. PMID 9139482.