Influence of carrier protein conjugation site and terminal modification of a GnRH-I peptide sequence in the development of a highly specific anti-fertility vaccine. Part I

American Journal of Reproductive Immunology

Volumn 48, Issue 6, 2002, Pages 361-371

  Ferro, Valerie A ^a   Khan, Mohammad A H ^a   Earl, Elizabeth R ^b   Harvey, Michael J A ^b   Colston, Angela ^c   Stimson, William H ^a  

^a UNIVERSITY OF STRATHCLYDE   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

^c Triveritas Ltd   (United Kingdom)

Author keywords

Anti fertility; Antibodies; C terminal; Conjugation; GnRH immunoneutralization; N terminal

Indexed keywords

AMINO ACID; ANTIBODY; CARRIER PROTEINS AND BINDING PROTEINS; CONTRACEPTIVE VACCINE; CYANAMIDE; CYSTEINE; DES 1 GONADORELIN I; GONADORELIN DERIVATIVE; GONADOTROPIN; MONOMER; PROTEIN; TESTOSTERONE; TETANUS TOXOID; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY BLOOD LEVEL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CASTRATION; CHEMICAL REACTION; CONTROLLED STUDY; DRUG CONJUGATION; DRUG EFFECT; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG SPECIFICITY; GENITAL SYSTEM; GONADOTROPIN BLOOD LEVEL; IMMUNIZATION; IMMUNOGENETICS; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN MODIFICATION; RAT; TESTIS; TESTOSTERONE BLOOD LEVEL; VACCINATION;

AMINO ACID SEQUENCE; ANIMALS; ANTIBODY SPECIFICITY; ATROPHY; BINDING SITES; CROSS REACTIONS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FOLLICLE STIMULATING HORMONE; GONADOTROPIN-RELEASING HORMONE; HORMONE ANTAGONISTS; IMMUNIZATION; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; LUTEINIZING HORMONE; MALE; MOLECULAR SEQUENCE DATA; OLIGOPEPTIDES; ORGAN SIZE; PEPTIDE FRAGMENTS; RATS; RATS, SPRAGUE-DAWLEY; SPERMATOGENESIS; STRUCTURE-ACTIVITY RELATIONSHIP; TESTIS; TESTOSTERONE; VACCINES, CONTRACEPTIVE;

EID: 0036902325     PISSN: 87558920     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1600-0897.2002.01120.x     Document Type: Article

References (42)

1. Ferro VA, Stimson WH: Anti-gonadotropin releasing hormone vaccines and their potential use in the treatment of hormone-responsive cancers. Biodrugs 1999; 12:1-12.
2. D'Occhio MJ: Immunological suppression of reproductive functions in male and female mammals. Anim Reprod Sci 1993; 33:345-372.
3. Ferro VA, O'Grady JE, Notman J, Stimson WH: Immunological castration using a gonadotropin-releasing hormone analogue conjugated to PPD. Food Agri Imm 1995; 7:259-272.
4. Ferro VA, Stimson WH: Immunoneutralization of gonadotrophin releasing hormone: A potential treatment for oestrogen-dependent breast cancer. Eur J Cancer 1997; 33:1468-1478.
5. Thau R: Anti-LHRH and anti-pituitary gonadotrophin vaccines: Their development and clinical applications. Scand J Immunol 1992; 36:127-130.
6. Moudgal NR, Jeyakumar M, Krishnamurthy HN, Sridhar S, Krishnamurthy H, Martin F: Development of male contraceptive vaccine - A perspective. Hum Reprod Update 1997; 3:335-346.
7. Talwar GP: Vaccines and passive immunological approaches for the control of fertility and hormone-dependent cancers. Imm Rev 1999; 171:173-192.
8. Simm MS, Scholfield DP, Jacobs E, Michaeli D, Broome P, Humprehys JE, Bishop MC: Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. Br J Cancer 2000; 83:43-466.
9. Talwar GP: Fertility regulating and immunotherapeutic vaccines reaching human trials stage. Hum Reprod Update 1997; 3:301-310.
10. Talwar GP, Singh O, Pal R, Chaterjee N: Vaccines for control of fertility and hormone-dependent cancers. Int J Immunopharm 1992; 14:511-514.
11. Pal R , Talwar GP: In Birth Control Vaccines, GP Talwar, R Ragupathy (eds). Austin, TX, RG Landes Company, 1995, pp 63-73.
12. Cook RB, Popp JD, Kastelic JP, Robbins S, Harland R: The effects of active immunisation against GnRH on testicular development, feedlot performance and carcass characteristics of beef bulls. J Anim Sci 2000; 78: 2778-2783.
13. Kiyma Z, Adams TE, Hess BW, Riley ML, Murdoch WJ, Moss GE: Gonadal function, sexual behaviour, feedlot performance and carcass traits of ram lambs actively immunised against GnRH. J Anim Sci 2000; 78:2237-2243.
14. Zeng XY, Turkstra JA, Van De Wiel DF, Guo DZ, Liu XY, Meloen RH, Schaaper WM, Chen FQ, Oonk HB, Zhang X: Active immunisation against GnRH in Chinese male pigs. Reprod Domest Anim 2001; 36:101-105.
15. Malmgren L, Anderson O, Dalin AM: Effect of GnRH immunisation on hormonal levels, sexual behaviour, semen quality and testicular morphology in mature stallions. Equine Vet J 2001; 33:75-83.
16. Ferro VA, Khan MAH, Latimer VS, Brown D, Urbanski HF, Stimson WH: Immunoneutralization of GnRH-I, without cross-reactivity of GnRH-II, in the development of a highly specific anti-fertility vaccine for clinical and veterinary use. J Reprod Imm 2001; 51:109-129.
17. Aithal HN, Knigge KM, Kartha S, Czyzewski EA, Toback FG: An alternative method utilizing small quantities of ligand for affinity purification of mono-specific antibodies. J Imm Meth 1988; 112:63-69.
18. Ferro VA, O'Grady JE, Notman J, Stimson WH: A comparison of adjuvants used to investigate the immunogenicity of a GnRH analogue in male rats. Vaccine 1996; 14:451-457.
19. Ferro VA, Stimson WH: Effects of adjuvant, dose and carrier pre-sensitisation on the immunisation efficacy of a GnRH analogue. Drug Des Discovery 1996; 14:179-195.
20. Silversides DW, Allen AF, Misra V, Qualtiere L, Mapletoft RJ, Murphy BD. A synthetic luteinizing hormone releasing hormone vaccine. I. Conjugation and specificity trials in BALB/c mice. J Reprod Immunol 1988; 13:249-261
21. Schaaper WM, Lankhof H, Puijk WC, Meloen RH: Manipulation of antipeptide immune response by varying the coupling of the peptide with the carrier protein. Mol Immunol 1989; 26:81-85.
22. Ladd A, Tsong Y-Y, Lok J, Thau RB: Active immunization against LHRH. I. Effects of conjugation site and dose. Am J Reprod Immun 1990; 22:56-63.
23. Goubau S, Silversides DW, Gonzalez A, Mapletoft RJ, Murphy BD: Immunization of sheep against modified peptides of gonadotropin releasing hormone conjugated to carriers. Domest Anim Endocrinol 1989; 6:339-347.
24. Ramasamy R, Wickremaratne C: Influence of N-terminal amino acids & conjugation position to carrier on specificites of antibodies elicited by malaria peptides. Indian J Med Res 1994; 99:21-26.
25. Gupta HM, Talwar GP, Salunke DM: A novel computer modeling approach to the structures of small bioactive peptides: The structure of gonadotropin releasing hormone. Proteins 1993; 16:48-56.
26. Singh V: Influence of immunogen modification on the gonadotropin releasing hormone antibody reactivity. Biochem Int 1992; 27:579-589.
27. Philips JR, Brouwer W, Edwards M, Mahler S, Ruhno J, Collins AM: The effectiveness of different rat IgG subclasses as IgE-blocking antibodies in the rat basophil leukaemia cell model. Immunol Cell Biol 1999; 77: 121-126.
28. Peters P.J, Gagliardo LF, Sabin EA, Betchen AB, Ghosh K, Oblak JB, Appleton JA: Dominance of immunoglobulin G2c in the antiphosphorylcholine response of rats infected with Trichinella spiralis. Infect Immun 1999; 67: 46661-46667.
29. Awoniyi CA, Reece MS, Hurst BS, Schlaff WD: Maintenance of sexual function with testosterone in the gonadotropin-releasing hormone-immunized hypogonadotropic infertile male rat. Biol Reprod 1993; 49: 1170-1176.
30. Rivier J, Rivier C, Perrin M, Porter J, Vale WW. In LHRH Peptides as Female and Male Contraceptives, GI Zatuchni, JD Shelton, JJ Sciarra (eds). Philadelphia, Harper & Row, 1981, pp 13-23.
31. Nikiforovich GV, Marshall GR: Conformation-function relationships in LHRH analogs. II. Conformations of LHRH peptide agonist and antagonists. J Pept Protein Res 1993; 42:181-193.
32. Bahk JY, Hym JS, Chung SH, Lee H, Lee BH, Choi WS: Stage specific identification of the expression of GnRH mRNA and localisation of the GnRH receptor in mature rat and adult human testis. J Urol 1995; 154:1958-1961.
33. Giri DK, Chaudhuri MK, Jayashankar R, Neelram GS, Jayaraman S, Talwar GP: Histopthological changes in reproductive organs of the male Wistar rats following active immunisation against LHRH. Exp Mol Pathol 1990; 52:54-62.
34. Kumar N, Savage T, DeJesus W, Tsong YY, Didolkar A, Sundaram K: Chronic toxicity and reversibility of antifertility effect of immunisation against GnRH in male rats and rabbits. Toxicol Sci 2000; 53:92-99.
35. Flanagan CA, Becker II, Davidson JS, Wakefield IK, Zhou W, Sealfon SC, Millar RP: Glutamate 301 of the mouse gonadotropin releasing hormone receptor confers specificity of mammalian gonadotrophin releasing hormone. J Biol Chem 1994; 269:22636-22641.
36. Finnerty M, Enright WJ, Morrison CA, Roche JF: Immunization of bull calves with a GnRH analogue-human serum albumin conjugate: Effect of conjugate dose, type of adjuvant and booster interval on immune, endocrine, testicular and growth responses. J Reprod Fertil 1994; 101:333-343.
37. Fujino M, Kobayashi S, Obayashi M, Shinagawa S, Fukuda T, Kitada C, Nakayama R, Yamakzaki I, White WF, Rippel RH: Structure-activity relationships in the C-terminal part of luteinizing hormone releasing hormone (LH-RH). Biochem Biophys Res Commun 1972; 49:863.
38. Davidson JS, McArdle CA, Davis P, Elario R, Flanagan CA, Millar RP: Asn 102 of the gonadotrophin releasing hormone receptor is a critical determinant of potency for agonists containing C-terminal glycinamide. J Biol Chem 1996; 271:15510-15514.
39. Singh V, Singh O, Kaul S, Talwar GP: The dominant role of amide group at C-terminus for recognition by antibody in primates against gonadotrophin releasing hormone. J Steroid Biochem 1985; 23:801-802.
40. Singh V: Immunospecificity and affinity studies on the monoclonal anti-goandotrophin releasing hormone (GnRH) antibodies: Monoclonals produced by azotized GnRH preferentially recognise to native GnRH. Biochem Int 1987; 15: 153-162.
41. Singh V: Structural requirement for the recognition of luteinising hormone releasing hormone (LHRH) by monoclonal and conventional anti-LHRH antibodies. Biochem Cell Biol 1986; 64:1372-1377.
42. Ghosh S, Jackson DC: Antigenic and immunogenic properties of totally synthetic-peptide-based anti-fertility vaccines. Int Imm 1999; 11:1103-1110.