| Keywords: | Contraceptives; Vaccines (human); World Health Organization (WHO); Gender. |
| Correct citation: | Sprenger, U. (1995), "Challenging the Immune System: The development of anti-fertility vaccines." Biotechnology and Development Monitor, No. 25, p. 2-5. |
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:
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.
Ute Sprenger
Burgsdorfstrasse 11
13353 Berlin, Germany
This article is based on: Ute Sprenger and Helen Zweifel (1994), Auswirkungen der modernen Biotechnologien auf Frauen in den Ländern des Südens. Study for the German Office for Technology Assessment (TAB), July/August 1994 (unpublished).
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.
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