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 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," 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 in Uganda 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 Hopkins 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 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 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 other vaccines' safety against all subtypes and various cross-mixes of the virus.

"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 Africa." Jackson, a pathologist and virologist, 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 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.

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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.

Contact: David March
Johns Hopkins Medical Institutions