Induction of specific immune response and suppression of fertility by B-cell-epitope-based mimovirus vaccine

Reproduction. 2011 Nov;142(5):659-66. doi: 10.1530/REP-11-0161. Epub 2011 Sep 9.

Abstract

SPINLW1 (previously known as eppin (epididymal protease inhibitor)) is a target under intense scrutiny in the study of male contraceptive vaccines. B-cell-dominant epitopes are now recognized as key parts of the induction of humoral immune responses against target antigens. The generation of robust humoral responses in vivo has become a crucial problem in the development of modern vaccines. In this study, we developed a completely novel B-cell-dominant-epitope-based mimovirus vaccine, which is a kind of virus-size particulate antigen delivery system. The mimovirus successfully self-assembled from a cationic peptide containing a cell-penetrating peptide of TAT49-57 and a plasmid DNA encoding both three SPINLW1 (103-115) copies and adjuvant C3d3. The male mice were immunized with the epitope-based mimovirus vaccine, which resulted in a gradual elevation of specific serum IgG antibody levels. These reached a peak at week 4. Mating for the fertility assay showed that the mimovirus vaccine had accomplished a moderate fertility inhibition effect and investigation into the mechanism of action showed that it did so by interfering with the reproductive function of the sperm but that it did not damage the structures of the testes or cause serum testosterone to decline. Our results suggest an ideal protocol for suppressing fertility in mice by an engineered mimovirus vaccine.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / drug effects
  • Antibody Formation / physiology
  • Biomimetics
  • Contraceptive Agents, Male / immunology
  • Contraceptive Agents, Male / pharmacology
  • Epitopes, B-Lymphocyte / immunology*
  • Female
  • Fertility / drug effects*
  • Fertility / immunology
  • HEK293 Cells
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Substrate Specificity / immunology
  • Testosterone / blood
  • Vaccines, Contraceptive / immunology*
  • Vaccines, Contraceptive / pharmacology*
  • Viruses / genetics
  • Viruses / immunology*

Substances

  • Contraceptive Agents, Male
  • Epitopes, B-Lymphocyte
  • Vaccines, Contraceptive
  • Testosterone