Babies whose mothers have HIV, but who are not HIV-infected themselves, are born with lower levels of specific proteins in their blood called antibodies, which fight infection, compared with babies not exposed to HIV, a new study has found. The finding, published today in the Journal of the American Medical Association, might explain in part why uninfected babies born to women with HIV have a higher risk of illness and death early in life.
Major programmes using antiretroviral drugs have successfully reduced the rate of mother-to-child transmission of HIV from 20-30 per cent to around five per cent in some areas of South Africa and to less than one per cent in developed countries. However, HIV-uninfected infants born to HIV-infected mothers in Africa are more prone to infections such as pneumonia and meningitis, and up to four times more likely to die before their first birthday, compared with babies born to HIV-negative women. Socioeconomic factors are thought to account partially for this discrepancy but differences in the babies' immune systems might also be important.
The new study, by scientists from Imperial College London and Stellenbosch University in South Africa, found that babies born to HIV-infected mothers had significantly lower levels at birth of antibodies against a range of bacterial infections (Hib, pertussis, pneumococcus and tetanus).
Antibodies, which bind to specific pathogens and direct immune cells to attack them, are transferred from mother to child through the placenta late in pregnancy. The study found lower levels of some specific antibodies in mothers with HIV, but also that less antibody is transferred from mother to child across the placenta.
Despite their low antibody levels at birth, the babies in the study responded well to vaccination: they produced similar levels of antibody to some vaccines and higher levels to other vaccines.
"It's likely that lower antibody levels in these babies contributes to lower protection against infection before the babies have received their vaccines," said Dr Christine Jones from the Department of Paediatrics at Imperial College London, the study's first author. "Although they appear more vulnerable in the first few months of life, the good news is that these babies respond well to vaccination. We might be able to protect them even better against infections, either by vaccinating them earlier or by vaccinating the mother in pregnancy. More research will be needed to establish what the best way of protecting these babies might be."
The study involved 109 HIV-infected and uninfected mothers in a community health centre in Khayelitsha, a rapidly-growing township in Cape Town, South Africa. The researchers measured antibody levels in the mothers at delivery and the infants at birth. They also assessed how the babies responded to routine vaccination by measuring the babies' antibody levels at four months, after they had received their routine vaccines.
Amongst the HIV-negative women in the study, a third also had low antibody levels, showing that protection against infection in their babies might also not be optimal in some women, who are otherwise perfectly healthy.
Dr Beate Kampmann, Reader in Paediatric Infection & Immunity at Imperial and the senior author of the study, said: "Around six million children under five die every year from infectious diseases, and a lot of these deaths are preventable by using existing vaccines. Studies like ours are helping us understand why certain infants might be especially susceptible to infections, and how we might tailor vaccination policies to protect vulnerable babies more effectively."
The Imperial team will soon begin a new project studying antibody levels in babies and mothers with and without HIV, among patient volunteers from Imperial College Healthcare NHS Trust. This work is funded by Imperial's Biomedical Research Centre, which was awarded by the National Institute of Health Research (NIHR).
The South Africa study was supported by funds from the European Society for Paediatric Infectious Diseases, the Thrasher Research Fund, the Elizabeth Glaser Pediatric AIDS Foundation and the Wellcome Trust.
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Notes to editors:
1. Journal reference: Jones C, Naidoo S, De Beer C, Esser M, Kampmann B and Hesseling A. Maternal HIV Infection and Antibody Responses Against Vaccine-Preventable Diseases in uninfected infants. JAMA, 2011; 305 (6): 576 - 584
2. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
3. The Elizabeth Glaser Pediatric AIDS Foundaton is a global leader in the fight against pediatric HIV and AIDS, and has reached nearly 11 million women with services to prevent transmission of HIV to their babies. It works at more than 5,100 sites in 17 countries to implement prevention, care, and treatment services; to further advance innovative research; and to execute strategic and targeted global advocacy activities in order to bring dramatic change to the lives of millions of women, children, and families worldwide. Anneke C. Hesseling, PhD, received the Foundation's International Leadership Award, a three-year grant focused on international investigations in PMTCT and HIV care and treatment, in support of this study. www.pedaids.org
4. The Thrasher Research Fund is dedicated to improving the health of children across the world. The Fund awards grants for pediatric research that offers substantial promise for meaningful advances in prevention, diagnosis and treatment of children's diseases. www.ThrasherResearch.org