, along with scientists from Johns Hopkins and other institutions worldwide,
have begun the first clinical safety trial in
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 by virus carried in their mother's milk.
Enrollment of the first newborn took place at
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
"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," says study protocol chair and pediatric infectious disease
specialist Laura Guay, M.D., who will lead 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," says Guay, an associate
professor at The Johns Hopkins University School of Medicine.
Guay notes 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 which breastfeeding can help prevent through nutrition and
ingestion of the mother's antibodies. Moreover, she says, it would be
potentially harmful to deny this key means of nutrition to the 80,000 newborns
who do not contract HIV each year from their infected mothers, either from
pregnancy, labor or delivery, or breast milk. Indeed, Guay points 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 local 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 while 10 others will get placebo saline solution.
Eligible candidates will undergo initial examination at
Mulago Hospital, in Kampala, 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 in four separate doses of 1
milliliter of vaccine each, over a period of three months. Participants will
then 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 the study was to be
carried out and participated in advance in educational seminars.
The goal of the
team is to eventually 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
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
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
, 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
, all of which are being studied 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, but has had genetic material from specific
strains of HIV inserted into it. The theory, according to researchers, is that
the human body could develop a cellular immunity to HIV by developing immunity
to its genetic components in the non-harmful 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
safety against all subtypes and various cross-mixes of the
"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,"
notes study co-investigator Brooks Jackson, M.D., M.B.A., professor and director
of pathology at Hopkins. "We hope this study will lead to more effective
research and treatment and more vaccine trials in infants in
Jackson, a pathologist and virologist, has studied HIV
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 currently live 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, 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, part of the U.S. National Institutes of
Health. 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.