The optimal way to make a lasting impact on the spread of HIV is through development of a preventative vaccine that will protect all individuals — including infants — from the virus.

Infants, especially those that are exposed to HIV through breast-feeding, are uniquely positioned to benefit from vaccine research. Researchers are able to pinpoint the source and timing of HIV infection in infants. Testing an effective vaccine among infants in areas with a high rate of mother-to-child transmission through breast-feeding would demonstrate results quickly. In addition, the existing health care infrastructure in the developing world is focused specifically on delivering vaccines to children during the first year of life. Vaccines have reduced many common childhood infections by up to 99 percent in the developed world, and are probably the single most effective public health measure available.

A vaccine that protects infants against HIV transmission through breast-feeding could set the stage for lifetime immunity. If the vaccine were successful, millions of children could be provided life-long protection, creating the first HIV-free generation. Research and testing of possible vaccines will help guide and accelerate overall HIV vaccine development.

The Foundation’s Pediatric HIV Vaccine Research Program seeks to address basic and pre-clinical research relevant to pediatric HIV vaccine design and development, including, but not limited to, the following topics:

• The study of breast-milk transmission of HIV;
• Pediatric immune responses to HIV;
• Identification of potential vaccines for pediatric populations; and
• Identification of obstacles to the conduct of clinical trials in infants.

2009 Pediatric HIV Vaccine Research Grants
Margaret E. Feeney M.D. M.Sc.
University of California, San Francisco
Analysis of HIV-Specific Lymphocytes in Infants using Single-Cell Microtools
Dr. Feeney’s project uses exciting new technology to understand more about T cells and their capacity to fight HIV infection in infants. In collaboration with Dr. Christopher Love of MIT, Dr. Feeney’s lab will be able to examine the functional capability of an infant’s HIV-specific T cells on a single cell level. The development of single-cell microtools, which are highly flexible and amenable to high-throughput analysis at relatively low cost, has potential to help define correlates of protective immunity in the pediatric population.

Barbara Payne, Ph.D.
University of Washington, Seattle, WA
The Role of Immune Activation and Natural Killer Cells in Acquisition and Control of Infant HIV-1
Dr. Payne’s lab will study a cohort of more than 400 mother-infant pairs from sub-Saharan Africa to determine the role of innate immunity in HIV transmission and infection. Innate immunity refers to the body’s ability to mount immediate responses to infection (as opposed to acquired immunity, which develops over time after infection occurs). Her project will study innate immunity and immune activation, comparing infants who subsequently do and do not acquire HIV-1 from their mothers, and similarly in acute infection in HIV-1-infected infants, comparing those who subsequently do and do not rapidly progress. These comprehensive analyses involving African HIV-1-exposed infants could potentially enable innovative rational design of an infant HIV-1 vaccine.

Nancy Haigwood, Ph.D.
Oregon National Primate Research Center/ Oregon Health & Science University
Analyzing the HIV-Specific Neutralizing Antibody Response and Repertoire in Newborn Macaques
Passive studies utilizing neutralizing antibodies (NAbs) have shown that high doses of NAbs can fully block infection with HIV in some animal models. Although it may be difficult to attain such high levels of NAbs in humans through maternal transfer or vaccination, there is evidence that even non-sterilizing levels of NAbs can reduce the infectivity of viruses in vivo and help reduce disease. Dr. Haigwood will study the development of NAbs and will contribute to understanding how antibody-based therapy can limit mother-to-child transmission of HIV.

Frank Kirchhoff, Ph.D.
University of Ulm, Germany
Factors affecting HIV-1 Infection in Human Breast Milk
Transmission through breastfeeding is a major cause of infant HIV infection in developing countries. However, the factors modulating the infectiousness of HIV in breast milk are poorly understood. We have recently demonstrated that screening of large peptide/protein libraries derived from human fluids allows us to identify novel natural inhibitory and enhancing factors that may play relevant roles in HIV pathogenesis and transmission. In this project, Dr. Kirchoff will apply this technology to identify as-yet-unknown natural agents involved in virus transmission by breastfeeding. The results will provide new insights into the mechanisms of mother-to-child HIV transmission by breastfeeding and might lead to new preventive strategies.

Heather Jaspan, M.D., Ph.D., F.A.A.P.
University of Washington, Seattle and University of Cape Town, South Africa
Influence of BCG Immunization on Immune Responses and Disease Progression in South African HIV-Exposed and -Infected Infants
In sub-Saharan Africa (SSA), more than 300,000 babies with HIV die each year. HIV-infected children develop AIDS and die faster in SSA than those in developed countries. An HIV vaccine that could protect newborns from HIV would be of great value in developing countries. Bacille Calmette-Guerín (BCG) vaccine is given to infants at birth in SSA to protect them from severe forms of TB. Dr Jaspan’s project will study immune cells in infants to determine the impact of BCG vaccination on immune responses to other vaccines. We will also compare the disease progression of those infants that become HIV-infected in the BCG or control arms. Our results will provide key insights into the effect of BCG vaccination on immune responses to HIV as well as to potential future HIV vaccines for children.