===== Over recent decades, researchers have been
exploiting new contraceptive methods to use in family
planning programmes in the South. Within the scope of
medical application of modern biotechnologies, the
development of anti-fertility vaccines is a new
approach. However, these new vaccines do not really
benefit the user, says Ute Sprenger. =====
Modern biotechnologies in the health care sector not
only serve as a basis for prevention, new diagnostic
methods and cures for diseases. They also make
intervention into the domain of human reproduction
possible through the development of a variety of new
methods and products to control fertility. While the
significance of artificial insemination is negligible
for the majority of people in the South, the
possibility to prevent pregnancy is of major
importance. Many advocates of population control policy
envisage anti-fertility vaccines, once on the market,
as a promising contraceptive. Unlike conventional
methods, such as the intra-uterine device, the pill,
hormone injections and implants, contraceptive vaccines
use the immune system to induce antibodies against
hormones or other molecules involved in human
reproduction. Although these vaccines can be used by
both men and women, most of the research is directed
towards women, as scientists perceive the female cycle
to be the easiest target.
Proponents of anti-fertility
vaccines claim that they offer a wider choice of family
planning methods. However, from a user s perspective
two questions need to be answered: (1) does this new
technology empower women to gain more autonomy over
their fertility?; and (2) does it improve their health?
STRATEGY
Over the last two decades world wide research on
fertility regulating vaccines has been conducted under
the auspices of the World Health Organization (WHO).
Some prototype vaccines have undergone or are currently
undergoing clinical trials in several countries. The
entirely new immunological approach is based on the
idea that a long-term contraceptive method, intended
for use in family planning programmes in countries with
low levels of medical care, should require little
motivation of the user, should be cheap, and should be
simple to apply by the provider.
The approach is an
integral part of the strategy of demographic control,
which has provided a series of long-lasting, provider-
dependent birth control methods since the 1960s. At a
1989 WHO symposium on the safety and efficacy of anti-
fertility vaccines the chairman summarized the debate:
"Foremost in my mind during these discussions was our
difficulty in assessing the urgency of the demographic
crisis. To the extent that the impact of that crisis
increases, the need for more effective family planning
technologies must increase. At the very least, failure
to develop something that may provide a more effective
technology would be to take a grave and unnecessary
risk."
APPROACHING THE HORMONAL CASCADE
The anti-fertility vaccines that are being researched
refer to the mode of action of conventional vaccines
against diseases. They are based on the stimulation of
the immune system, but unlike anti-disease vaccines
which target foreign substances, anti-fertility
vaccines evoke antibodies against the body s own
substances like molecules. As a result, the body s
self-protection is reprogrammed to attack targets the
body normally tolerates. To that end, the targeted,
normally tolerated molecule, has to be linked to a
foreign protein, rendering the entire product foreign
and inducing an antibody reaction.
Currently six
variations of these vaccines are at different stages of
development. Commonly identified as the most suitable
candidates for vaccine development are certain
molecules on the surface of the sperm and the egg,
molecules on the surface of the fertilized egg and the
early embryo, and human chorionic gonadotrophin (hCG).
The hormone hCG is secreted by the surface of the early
embryo to remain implanted in the womb. If hCG is
blocked, the level of progesterone declines and the
blastocyst (fertilized egg 5 days after fertilization)
is expelled, thereby terminating the pregnancy. Anti-
hCG vaccine consists of a part of the hormone linked to
a bacterial or viral carrier inducing the antibody
reaction. However, researchers admit that it is not
known exactly how immunization against hCG impairs
fertility.
The prototype version of an anti-hCG vaccine
consist of an immunogen, formed from a (synthetic)
peptide of hCG conjugated to a toxoid carrier molecule,
mixed with an immunostimulant, and suspended in a fluid
vehicle.
Other more advanced approaches that have reached
clinical trials are vaccines inhibiting the
gonadotrophin-releasing hormone (GnRH), produced within
the diencephalon. The diencephalon (hypothalamus) is a
part of the brain that lies beneath the thalamus where
the flow of steroid hormones is regulated. The hormone
is involved in the fine-tuning of these steroid
hormones. Because this vaccine, developed by the
Population Council, brings the hormonal cascade to a
total standstill both male and female recipients need
synthetic steroid hormone replacement in order to
counteract unwanted side-effects such as the loss of
bone density. In women a reaction similar to an
artificial menopause is induced.
The first clinical trials with anti-fertility vaccines
began in the 1970s. Until early 1994, about 400
experimental subjects, mainly women, were involved. By
far the most researched and clinical tested are anti-
hCG vaccines. Two prototypes, developed by National
Institute of Immunology (NII) and the Special Programme
of Research, Development and Research Training in Human
Reproduction (HRP), are being tested on women in India,
Australia, Brazil, Chile, Dominican Republic, Finland
and Sweden. The NII has started experiments with live
vectors. In order to prolong antibody response, beta-
hCG genes were transferred into a vaccinia virus, which
reproduces itself. The stability of the vaccinia,
pathogen of cowpox, is controversial.
ACTORS INVOLVED
In the early 1970s a group of scientists came together
at the WHO to discuss the impact of the advances in
biosciences on birth control. In 1973 the WHO
established the Task Force on Vaccines for Fertility
Regulation, as part of the HRP. The HRP, today under
the auspices of the United Nations Development
Programme, the United Nations Population Fund (UNFPA),
the WHO and the World Bank, concentrates on research
and development of contraceptive methods and services
in developing countries and its social, ethical, legal
and regulatory issues.
The Task Force acts as a global coordinating body for
anti-fertility vaccine R&D in the various working
groups and supports research on different approaches,
such as anti-sperm and anti-ovum vaccines and vaccines
designed to neutralize the biological functions of hCG.
The Task Force has succeeded in developing a prototype
of an anti-hCG-vaccine.
Currently five large and a number of small institutions
are conducting research on anti-fertility vaccines. The
five large institutions involved are:
* WHO/HRP, Switzerland. Major supporters of the
programme are the governments of Sweden, United
Kingdom, Norway, Denmark, Germany and Canada, as well
as the UNFPA and the World Bank.
* The Population Council, United States. Among the
Council s financiers are the Rockefeller Foundation,
the National Institutes of Health and the US Agency for
International Development.
* National Institute of Immunology, India. Major
financiers are the Indian government, the Canadian
International Development Research Centre and the
Rockefeller Foundation.
* The Contraceptive Development Program (CONRAD),
United States. Publicly funded.
* The Center for Population Research at the National
Institute of Child Health and Development/the National
Institutes of Health (NICHD/NIH), United States.
Publicly funded.
Various smaller research teams conducting basic, pre-
clinical research and clinical trials with anti-
fertility vaccines are based at universities in Kenya,
Germany and France, or at institutes like the Medical
Research Council (MRC) in England. They receive public
funds or are supported by pharmaceutical companies such
as Schering (Germany) or Organon (the Netherlands).
According to WHO/HRP, of the approximately US$ 57
million spent annually on overall contraceptive
research, an estimated 10 per cent is devoted to anti-
fertility vaccines. WHO/HRP figures indicate an
expenditure of US$ 946,000 or 16.3 per cent of the
programme budget in 1992. According to David Griffin,
manager of HRP Vaccines Task Force, the Programme has
spent approximately US$ 10 to 11 million on anti-
fertility vaccines between 1973 and 1993.
HAZARDS
The following hazards concerning contraceptive vaccines
have been suggested:
Auto-immune disorders and cross-
reactivity. In order to achieve immuno-contraception,
the body s mechanism of self-protection must be induced
to attack the molecules on the sperm, eggs or hormones.
Though researchers involved emphasize that until now no
side-effects or unintended reactions of the immune
system have occurred, it can not be excluded that
allergic reactions, cross reactions on others then the
target-cell or molecules, or auto-immune diseases might
appear in the medium or long-term. After all, the
immune system is an open system that weakens with
stress, injuries, illness, and age.
Normally the immune
system distinguishes between what immunologists call
"self" and "non-self": it tolerates the body s own
substances like tissue, cells, proteins and attacks
foreign substances. However, since the 1960s the number
of diseases of "unknown etiology" classified as immune-
system-related diseases has been increasing. An
estimated two-thirds of the adults in Europe and North
America suffering from an auto-immune disorders are
women. Particularly in view of an increase in immune-
related diseases it may be risky to manipulate the
highly complex mechanism of "self" tolerance of the
human organism.
Moreover, there is a possibility of a cross-reactivity
of vaccine candidate antibodies with other hormones.
For instance, the hormone hCG is a member of the family
of glycoprotein hormones, which also includes lutropin
(LH), follitropin (FSH) and thyrotropin (TSH). Parts of
the structure of these four hormones are similar, so
that antibodies elicited against hCG may interfere with
other pituitary hormones. Some experts have also warned
of a risk of an auto-immune attack against the ovaries.
Unexpected cross-reactivity has already been observed
against pancreatic cells.
Other unexpected side-effects. Trials under the
auspices of WHO/HRP at the Karolinska Hospital in
Stockholm, Sweden were suspended in June 1994.
According to a programme document, the first seven
volunteers to receive the vaccine all experienced
totally unexpected side-effects which included pain at
the injection site, fever and sterile abscess
formation. The Task Force researchers suspect batch
related causes and are investigating the material to
eliminate side-effects.
Medical needs. Even if the
technology itself gets more sophisticated and some of
the medical problems can be solved, the danger remains
that anti-fertility vaccines will be used in regions
lacking the necessary medical care. Angeline F.
Schrater, women s health advocate, describes the
imperative structural medical needs of anti-fertility
vaccines as follows: "Women must be screened for
pregnancy before immunization and monitored for
protective immunity after. They also must be tested for
allergic reaction to the vaccine prior to each
injection. Further, reversibility cannot be guaranteed
and women must be so informed."
Abuse. Due to the lack of user control, the approach
also bears a high potential for abuse. The method might
encourage efforts to control female fertility for
demographic purposes as it is easy for medical or
paramedical staff to administer without a woman s full
knowledge or consent. The design of anti-hCG vaccines
allows the antagonist to be coupled with vaccines
against diseases, i.e. diphtheria, tetanus or measles.
As admitted at the 1989 WHO-Symposium, due to this
potential for abuse, the method might even discredit
health care and general vaccination programmes
conducted in countries of the South.
Duration. It is
generally assumed that the final product will be a
anti-fertility vaccine, administered by injection or
orally and lasting for one to two years. Once the
treatment is administered it cannot be discontinued and
women or men affected must wait until the immunological
effect decreases. Though the WHO/HRP is considering
counter-vaccines to "switch on" fertility if required,
nothing concrete has been researched so far. In fact,
when and whether fertility is regained depends not only
on the individual immune response, but also on the
ethnic response. Within the scientific community there
is debate about irreversibility and thus "non-surgical
sterilization" as appreciated effect.
Working. Clinical trials with women have shown that the
differences in immune response is not only relevant
concerning reversibility but for the effectiveness of
the contraceptive as well. Thus it is reported that
women in clinical trials with the Indian made prototype
conceived and some even gave birth to children. Yet
nothing is known about the possible ill-effects on the
children of these vaccinated women, and no research on
this is being carried out.
PROTESTS
More than twenty years after researchers began to
investigate the use of antibodies for contraceptive
purposes, many related questions concerning efficacy,
safety and the ability to meet women s needs, remain
unanswered. Additionally, by supporting a practice
based on population policy they are likely to undermine
women s rights for reproductive self-determination.
During the last decade, in many Southern countries
demographic targets were introduced, and field workers
and para-medical staff are stimulated to distribute
effective contraceptives to reduce the birth rates.
Long-term, provider-dependent methods are seen as most
suitable to meet these requirements. Considering that
there seems to be a growing tendency to oblige poor
women from the South to control their fertility, it is
doubtful whether such a climate has stimulated the
right of women to determine their family planning
methods, or even whether they want to use
contraceptives at all.
Certainly, women and men need access to safe and
convenient methods of birth control as well as safe
methods of abortion. But will women, being at the
receiving end of modern contraceptive R&D yet again, be
content with this new kind of provider-dependent and
invasive vaccine? Many may not, as shown by the appeal
of more than 400 groups advocating women s health, from
about 40 countries (including Australia, Chile,
Germany, India, USA and Zimbabwe). They recently called
for the termination of research on anti-fertility
vaccines, and for a re-orientation of contraceptive
research, away from the technology fix. Instead of
demographic considerations directing contraceptive
research, the research should enabling people to gain
control over their own fertility.
All rights reserved. No parts may be reproduced,
stored or transmitted in any form without prior permission
of the author.
This article is based on: Ute Sprenger and Helen
Zweifel (1994), Auswirkungen der modernen
Biotechnologien auf Frauen in den Laendern des Suedens.
Study for the German Office for Technology Assessment
(TAB), July/August 1994.
Additional Source
UNDP/UNFPA/WHO/World Bank Special Programme for
Research, Development and Research Training in Human
Reproduction (1995), Annual Technical Report 1994.
Geneva: World Health Organization.
Homepage