Immunocontraceptive effect of izumo and enhancement by combination vaccination

被引:32
作者
Naz, Rajesh K. [1 ]
机构
[1] W Virginia Univ, Sch Med, Hlth Sci Ctr, Dept Obstet & Gynecol,Reprod Immunol & Mol Biol L, Morgantown, WV 26505 USA
关键词
contraceptive vaccine; Izumo; sperm; antigens; antisperm antibodies; infertility; SPERM-EGG FUSION; DNA VACCINE; MOUSE; PEPTIDE; PROTEIN; SP56; FERTILITY; CLONING; EXPRESSION; PREGNANCY;
D O I
10.1002/mrd.20783
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sperm proteins are being investigated for their applications in the development of contraceptive vaccines (CV) in several laboratories. In the present study, various synthetic peptides based upon four sperm proteins, namely Izumo, fertilization antigen-1 (FA-1), YLP12, and SP56 that are involved in various steps of the fertilization cascade were examined for their immunocontraceptive effect. The synthetic peptides were conjugated to four carrier proteins namely keyhole limpet. hemocyanin (KLH), bovine serum albumin (BSA), chicken gamma-globulin, and chicken ovalbumin. Female mice were immunized with various peptide vaccines and each booster injection was given with the peptide conjugated to a different carrier protein. Two different fertility trials with different doses of the peptide vaccines were conducted to examine the contraceptive effect. Injection of 150 mu g of the peptides (Trial 11) caused a significantly higher immune response in serum as well as in the vaginal tract causing enhanced contraceptive A effect than those observed after injection with 75 mu g of the peptides (Trial 1). Immunization with the peptide vaccines based upon lzumo, which is involved in 4 sperm-egg plasma membrane fusion, caused a significant reduction in fertility. The contraceptive A effect was enhanced by immunizing with the peptides A based upon other antigens (FA-1, YLP12, and SP56) resulting in an overall 73.33% reduction in fertility. When the antibodies against the peptides disappeared after >9-10 months from circulation and genital tract, all the animals regained fertility. These findings indicate for the first time that the immunization with Izumo and other sperm peptides namely FA-1, YLP12, and SP56 induces antibodies in serum and A genital tract that cause a reversible long-term contraceptive effect in female mice. The data further A A indicate that the proteins involved in sperm-egg fusion can also be used for contraceptive vaccine development. The contraceptive effects are enhanced by immunizing with the multipeptide vaccines.
引用
收藏
页码:336 / 344
页数:9
相关论文
共 32 条
[1]   Advances in immunology - Vaccines and vaccination [J].
Ada, G .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (14) :1042-1053
[2]   Immunocontraceptive vaccines for human use [J].
Aitken, RJ .
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2002, 57 (1-2) :273-287
[3]   A POTENTIAL FUSION PEPTIDE AND AN INTEGRIN LIGAND DOMAIN IN A PROTEIN ACTIVE IN SPERM-EGG FUSION [J].
BLOBEL, CP ;
WOLFSBERG, TG ;
TURCK, CW ;
MYLES, DG ;
PRIMAKOFF, P ;
WHITE, JM .
NATURE, 1992, 356 (6366) :248-252
[4]   TISSUE-SPECIFIC AND SPECIES-SPECIFIC EXPRESSION OF SP56, A MOUSE SPERM FERTILIZATION PROTEIN [J].
BOOKBINDER, LH ;
CHENG, A ;
BLEIL, JD .
SCIENCE, 1995, 269 (5220) :86-89
[5]   SPERM-EGG RECOGNITION IN THE MOUSE - CHARACTERIZATION OF SP56, A SPERM PROTEIN HAVING SPECIFIC AFFINITY FOR ZP3 [J].
CHENG, A ;
LE, T ;
PALACIOS, M ;
BOOKBINDER, LH ;
WASSARMAN, PM ;
SUZUKI, F ;
BLEIL, JD .
JOURNAL OF CELL BIOLOGY, 1994, 125 (04) :867-878
[6]  
Ferro VA, 1999, BIODRUGS, V12, P1
[7]   AM67, a secretory component of the guinea pig sperm acrosomal matrix, is related to mouse sperm protein sp56 and the complement component 4-binding proteins [J].
Foster, JA ;
Friday, BB ;
Maulit, MT ;
Blobel, C ;
Winfrey, VP ;
Olson, GE ;
Kim, KS ;
Gerton, GL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (19) :12714-12722
[8]   Failure of female baboons (Papio anubis) to conceive following immunization with recombinant non-human primate zona pellucida glycoprotein-B expressed in Escherichia coli [J].
Govind, CK ;
Gupta, SK .
VACCINE, 2000, 18 (26) :2970-2978
[9]   Development of mouse-specific contraceptive vaccines: infertility in mice immunized with peptide and polyepitope antigens [J].
Hardy, CM ;
Clydesdale, G ;
Mobbs, KJ .
REPRODUCTION, 2004, 128 (04) :395-407
[10]  
Hardy CM, 1999, MOL REPROD DEV, V52, P216, DOI 10.1002/(SICI)1098-2795(199902)52:2<216::AID-MRD13>3.3.CO