Contraceptive Vaccines Flashcards
what is the principle of contraceptive vaccines?
To use the immune system to limit fertility
what is a contraceptive vaccine?
A vaccine that induces an autoimmune response to components of the reproductive system, leading to infertility / sub fertility.
what’s the function of the immune system?
- detects invading agents
- destinguishes them from organisms cells
- responds to/ clears the invading agent
why do we need new contraceptives?
current contraceptive options have limitations
list the antibodies and their function;
IgM = agglutination, first antibody of immune response
IgG = most abundant in internal fluids
IgA = must abundant in secretions
IgE = antiparasite action, allergies
IgD = mainly on lymphocyte surface
Describe the constituents of a vaccine
Antigen
Adjuvant (non-specific activates immune system)
What antibodies cross the placenta?
IgG
Why do we need new contraceptives?
No new ones in 50 years
Limited ones available and most of them dont reach third world countries or are too expensive
Whats a current vaccine that is effective on wild life?
GonaCon
Describe Gonacon structure?
- It is GnRH conjugated via two amino acids to KLH (limpet haemocyanin)
(KLH is very soluble and many GnRH may bind)
- Emulsified in mycobacterial and oil adjuvent (contains m.avium-produces memory immune response)
What is the purpose of the KLH conjugated to GonaCON?
KLH is foreign and stimulates the immune system, as it is conjugated to GnRH the immune system then starts to attack GnRH thus being effective at making animals infertile.
What is KLH replaced by nowadays?
Blue protein
What is GonaCon effective against?
White tailed dear Elk Wild Horses Swine Bison Domestic Cats Rats
What are things to consider when designing contraceptive drugs in humans?
Human considerations;
- Is it a contraceptive or abortifacient effect (ethics, morals of religious groups/ people etc)
- Reliability
- Reversibility!
- Delivery system (mode, frequency, dont want daily injections!!)
What are things to consider when designing contraceptive drugs in animals?
Animal considerations
- Wild/Feral or domestic
- Reliability (can herd immunity be attained?.)
- Reversibility
- Delivery system (mode, frequency)
- Interspecies cross reactivity (will making possum infertile lead to cows also becoming infertile?)
What could be potential targets of contraceptive vaccines?
Reproductive Hormones Gametes Trophectoderm Placenta Milk Proteins
Describe reproductive hormones that could be targeted?
GnRH
LH and FSH
Progesterone and Estrogen
Highly Conserved
- Can manipulate these to create subfertility
Considerations;
- Systemic Side effects?
Describe how contraceptive vaccines could target ovum?
Ovum
- Could target ZP3 as all ovum have this (highly conserved across species)
- Loss of ZP3 would disrupt ovarian function
- Preventing sperm/oocyte binding
Describe how contraceptive vaccines could target sperm
Sperm
- Males or in female reproductive tracts
- Could use systemic or mucousal immunity
- Problem ; high numbers of sperm to target
Describe how contraceptive vaccines could target trophectoderm?
- Trophoblast surrounds the pre-implantation blastocyst
- Could prevent implantation
- Antigens are only expressed on preimplantation
Describe placental targets for contraceptive vaccines
- Abortifaction
- Ethical issues about using it in humans or animals
Describe how milk production could be targeted;
Mainly useful for marsupials
- Short gestation then long lactation in pouch phase
- Lack of lactation = death
Of the potential immune system targets, what branches of the immune system to they activate?
Hormones - Systemic humoral IgG Gametes - Mucosal immunity - Cell-mediated immunity - Complement activation Placenta - Cell-mediated immunity Milk Proteins - Mucosal IgA
Most ensure correct targets
What are some methods of delivery and who would they be used on?
Injection - Humans and domestic animals Baits - Wild/feral animals Recombinant vectors - Wild/feral animals
Describe how the bait system works;
Oral ingestion activates mucosal immunity
Describe how the recombinant vector works
- Interspecies specificity of the vector (virus, parasite)
- Interspecies specificity of the antigen
What is a current vaccine under trail that may prevent women from becoming pregnant?
Immunisation against hCG using beta chain
- Produced large quantities of hCG Ab
- No pregnancy in nearly all women
What is a $50 million prize being offered for
A development of a vaccine that targets both cats and dogs
- targets both sexes
- cheap
- single administration
What vaccine did larrys students design?
SPRASA
- Discovered as the antigen or antisperm antibodies in infertile men
- Expressed only in sperm/testis/ovaries
What were the results of the SPARSA study?
10 mice immunised with SPARSA
- 7 mice infertile after 5 attempts at mating
- 3 pregnant after 2 time tries.
What were the conclusions of SPARSA
Little effect on ovarian follicles-mating behaviour unaffected