Scientists at Makerere University in Kampala, Uganda,
along with scientists from Johns Hopkins and other
institutions worldwide, have begun the first clinical
safety trial in Africa of a vaccine to prevent
mother-to-child transmission of HIV through breastfeeding.
Breast milk is a leading route of infection in the
developing world, according to the United Nations World
Health Organization, which estimates that each day 1,800
newborns are infected with the AIDS virus, 30 percent to 40
percent of them by virus carried in their mother's milk.
Enrollment of the first newborn took place at Mulago
Hospital in Kampala. The so-called phase I study is
designed to test the safety of injecting newborns with the
vaccine, formally known as ALVAC-HIV (vCP1521). If the
vaccine is found to be safe in this study, and if it is
later shown to be effective in reducing the chance of
infants' becoming infected during breastfeeding,
researchers estimate that it could potentially stop up to
8,000 of Uganda's 22,000 infections a year in children.
Initial results are expected by mid-2007.
"A vaccine is the easiest way to help prevent
mother-to-child transmission of the disease, as healthy
alternatives to breastfeeding, such as infant formula, are
not available or affordable to most new mothers in the
developing world, many of whom do not know they are HIV
positive," said study protocol chair and pediatric
infectious disease specialist Laura Guay, who will lead
Johns Hopkins' efforts.
"Vaccines often involve several injections over a
short period of time, whereas other drug therapies that
might prevent transmission are less convenient and must be
taken daily over a longer period of time and potentially
have more side effects," said Guay, an associate professor
at the School of Medicine.
Guay noted that discouraging breastfeeding altogether
is not a practical option for many women because the lack
of safe alternatives increases five- to sevenfold a
newborn's chances of dying of pneumonia or diarrhea,
illnesses that breastfeeding can help prevent through
nutrition and ingestion of the mother's antibodies.
Moreover, she said, it would be potentially harmful to deny
this key means of nutrition to the 80,000 newborns in
Uganda who do not contract HIV each year from their
infected mothers, either from pregnancy, labor or delivery,
or breast milk. Indeed, Guay pointed out that the Ugandan
Ministry of Health has identified development of a vaccine
as a key priority for reducing the country's high HIV
transmission rates.
The Ugandan-led study will involve 50 infants born to
HIV-positive mothers in the Kampala area, all of whom are
otherwise in general good health, with key immune CD4 cell
counts of 500 cells per cubic milliliter of blood or
greater. Forty infants will be randomly assigned to receive
the vaccine; 10 others will get placebo saline solution.
Eligible candidates will undergo initial examination
at Mulago Hospital and make later visits to
Makerere-Hopkins Research Clinic, which specializes in AIDS
research and care, allowing participants ready access to
facilities for checkups and testing that will all be
provided free of charge. Once enrolled, infants will be
injected over a period of three months with four separate
doses of 1 milliliter of vaccine. Participants then will be
closely monitored through regular physical examinations and
blood tests for the duration of the study, which is
expected to last two and a half years. A group of local
community members provided advice on how to carry out the
study and also participated in educational seminars in
advance of its start.
The goal of the Johns Hopkins team is eventually to
find a vaccine that will allow infants to develop immunity
to HIV just as they would to polio, diphtheria and
hepatitis B after vaccination for those disorders. Many of
these vaccines, researchers point out, are already combined
into a single vaccination. The goal is to one day provide
an AIDS vaccine as part of a child's regular vaccination
program.
Previous research using an ALVAC-HIV vaccine in adults
in Uganda showed it to be safe, but it is not yet known if
it is effective in preventing infection. In 2005, a phase I
study done in newborns in the United States using a similar
ALVAC-HIV vaccine found that the vaccine was very safe.
Related clinical research from other institutions using the
same vaccine is under way in Thailand involving 16,000
participants, a much larger sample because researchers
there are testing the vaccine's broad effectiveness rather
than its initial safety.
However, research in monkeys has shown that ALVAC-SIV
vaccine was successful in preventing oral transmission
through milk of simian immunodeficiency virus, or SIV, in
11 of 17 newborns given the vaccine.
The ALVAC-HIV vaccine is one of at least five HIV
vaccines under study in Africa, all of which are being
tested in adults. It is manufactured by extracting cell
cultures that have been grown in embryonated chicken eggs.
The cell cultures contain live and weakened canarypox
virus, which does not infect humans, that has had genetic
material from specific strains of HIV inserted into it. The
researchers' theory is that the human body could develop a
cellular immunity to HIV by developing immunity to its
genetic components in the nonharmful canarypox virus. More
than 20 other test vaccines against the disease are in
various stages of early development.
Studies are proceeding in multiple countries to assess
other vaccines' safety against all subtypes and various
cross-mixes of the virus.
Co-investigator Brooks Jackson, professor and director
of Pathology at Johns Hopkins, said, "A major advantage to
this kind of research is that it opens up access to better
AIDS care — including medications, regular checkups
and home care — to the people of sub-Saharan Africa,
where the need is great. We hope this study will lead to
more effective research and treatment and more vaccine
trials in infants in Africa." Jackson, a virologist as
well as a pathologist, has studied HIV disease in Africa
for the past 16 years.
According to the latest statistics from the United
States Centers for Disease Control and Prevention, in 2004
more than 1 million Americans were currently living with
HIV, the virus that causes AIDS. However, the advent of
antiretroviral therapy and better understanding of how to
prevent transmission from mother to child have dropped the
annual number of pediatric cases from nearly 2,000 in the
early 1990s to under 200 in recent years, the births mostly
to mothers who did not know they were HIV positive.
Funding for the study is provided by the National
Institute of Allergy and Infectious Diseases. Vaccine is
being supplied by the manufacturer, Sanofi Pasteur, a
division of Sanofi-Aventis. Neither Guay nor Jackson
receives any financial benefit from the manufacturer for
their participation.
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