Semester

Fall

Date of Graduation

2011

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Rajesh K Naz

Committee Co-Chair

Christopher Cuff

Committee Member

Stephen Graber

Committee Member

Vazhaikkurichi Rajendran

Committee Member

David Weissman.

Abstract

Immunomodulation at the fetal-maternal interface is essential for the establishment and maintenance of pregnancy. Several interleukins have been shown to be key in this process. Leukemia inhibitory factor (LIF), a member of the interleukin-6 family of proteins, is vital for blastocyst implantation in both humans and mice. LIF is expressed by the uterine epithelium and stromal cells surrounding the blastocyst prior to implantation and acts via binding to the LIF receptor expressed on the endometrium. This study investigates the contraceptive effect of a vaccine prepared with peptides derived from LIF and LIF receptor in the murine model. The vaccine was created by conjugating the LIF and LIF receptor peptides to various carrier proteins. Vaccines were administered to female mice by intramuscular, subcutaneous or intranasal immunization. The contraceptive effect of the vaccine was investigated by mating vaccinated animals and counting the number of pups born. Immunization of female mice with the LIF/LIF receptor peptide vaccine induced peptide-specific antibody titers (IgG and IgA) in the sera as well as locally in the genital tract. These antibodies provide significant reductions in fertility as compared to controls. Targeting mucosal surfaces with intranasal immunization appeared to further reduce litter size in vaccinated animals. Peptide-specific antibodies were shown to remain in immunized mice up to 11 months after their final immunization. LIF/LIFR peptide antibodies not only reduced LIF bioactivity in vivo, they also neutralized LIF biological function in an in vitro assay. These studies suggest that LIF/ LIF receptor is an attractive target for immunocontraception.

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