DEVELOPMENT OF IMMUNOCONTRACEPTIVES

  • Miller, Chris J (PI)
  • Bigazzi, Pierluigi (PI)
  • Bleil, Jeffrey (PI)
  • Saling, Patricia (PI)
  • Langer, Robert (PI)
  • Myles, Diana (PI)
  • Overstreet, James (PI)
  • Primakoff, Paul (PI)
  • Hecht, Norman (PI)
  • Morris, David (PI)
  • Florman, Harvey (PI)

Project: Research project

Project Details

Description

The focus of this Center is immunocontraception in which the target is
surface molecules of the sperm cell. Immunocontraception directed against
the gamete surface is the most sophisticated barrier method of
contraception, where the barrier is at the molecular level. Remarkable
advances have occurred recently in immunology, molecular biology and
fertilization research. These advances have combined to open possibilities
for immunocontraception that were previously imagined but unattainable. Project #1 (Primakoff) proposes to develop a birth control vaccine for
women which blocks fertilization and is effective, safe and widely
acceptable. The vaccine uses the sperm surface protein PH-20, the only
sperm protein shown to give 100% effective contraception in female animal
model. Project #2 (Myles) proposes two novel strategies for development of male
immunocontraceptives. The first strategy uses a vaccine based on a single
epitope of the PH-30 protein. This epitope is required in fertilization
and is present on epididymal but not testicular sperm. The second
strategy, passive immunization, involves sustained release of monoclonal
antibodies in the male which recognize either PH-20 or PH-30, sperm
proteins required for fertilization. Project #3 (Bigazzi) proposes another comprehensive strategy for a male
vaccine. In this case, male mice and monkeys will be immunized with PH-20
or peptides from PH-20. The immunization protocols, adjuvants and peptides
will be screened to find those that induce infertility an avoid
inflammation in the testis. Project #4 (Bleil) proposes the isolation of a unique type of
immunocontraceptive monoclonal antibody (Mab). The Mab will inactivate
sperm in the female reproductive trace by inducing a premature acrosome
reaction. Project #5 (Saling) is based on Saling's discovery of a sperm plasma
membrane tyrosine kinase, p95, that has properties of a receptor for ZP3.
Saling proposes to clone cDNAs for mouse and human p95 and test them as
contraceptive immunogens in mice and primates. Project #6 (Langer) is focused on a sustained release device for antigens
that vies long-term, high titer immunization, the ideal features for a
contraceptive vaccine. The further refinement of the polymeric release
device developed by Langer and its application to contraceptive vaccines is
proposed.
StatusFinished
Effective start/end date9/30/912/29/08

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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