Clinical guidelines: PMTCT (prevention of mother-to-child transmission). 1 year earlier than HUU patients, and SB-649868 maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life. INTRODUCTION Vaccination is essential to combat infectious mortality and morbidity in children under 5 years of age (1). Despite the availability of effective vaccines, 6 million children die from infectious diseases SB-649868 annually, mainly in low- to middle-income countries where HIV is often prevalent (2, 3). While a lack of access to vaccines surely is the most important contributor to the high number of vaccine-preventable deaths in these regions, it is unclear if vaccination is equally protective in all children. Globally, more than 2 million babies are born to HIV-infected mothers every year (4). Programs for vertical transmission prevention of HIV (VTP) have reduced vertical infection to well below 10% (5), therefore nearly 2 million HIV-exposed but uninfected (HEU) infants are born annually. Recent evidence indicates that HEU infants are at a higher risk of infectious morbidity and mortality than their HIV-unexposed, SB-649868 uninfected (HUU) peers (6C12). The underlying reason(s) for this phenomenon are still unclear but are possibly multifactorial; severity of maternal HIV disease (13), avoidance of breastfeeding (14C16), and differences in microbial exposures (17) have all been postulated. Furthermore, exposure to HIV itself (18), as well as to antiretroviral drugs for VTP, may also directly impact the HEU infant’s immune system (19, 20). Suboptimal response to vaccination thus has been suggested to contribute to the increased infectious burden of HEU. This notion has been supported by several studies, which documented low vaccine-specific antibody titers in HIV-infected mothers and attenuated vaccine-specific antibody levels in HEU compared to HUU infants (21C24). These differences have been ascribed to a compromise in maternally transferred antibodies, differing antibody half lives (24), and altered responses to vaccination (21, 22). To date, however, studies have only investigated vaccine responses in either short-term cohorts or in cross-sectional analysis (21C24), thereby not addressing long-term vaccine-induced immunity in HEU infants (14). A longitudinal analysis of HEU responses to vaccination is required to better understand how the rapidly expanding population of HEU infants responds to childhood vaccination. To this end, we established a birth cohort study in South Africa, a country with an antenatal HIV prevalence of 30% (25), and monitored HEU and HUU infants from 2 weeks up to 2 years of life (12), evaluating their vaccine-specific immune responses. Based on the published literature (21, 22, 24), we expected to find lower prevaccine-specific antibody titers in the HEU than in the HUU infants, followed by a higher level of response to certain vaccines in HEU than in HUU infants after vaccination. However, given the lack of data, we were not able to predict HEU infants’ immune response to booster doses and the longevity of the resulting immune response. Our study aimed to provide this missing information. MATERIALS AND METHODS Cohort composition. A prospective cohort study commenced in March 2009 in Cape Town, South Africa, to evaluate immune function in HEU and HUU infants over the first 2 years of life (12). The research ethics committees of Stellenbosch University and the University of British Columbia both approved Mouse monoclonal to MYST1 the study. Infants of mothers with known HIV infection status were recruited at birth from the Tygerberg Academic Hospital (TAH) labor ward and evaluated at 0.5, 1.5, 3, 6, 12, 18, and 24 months. HIV infection status of the mothers was confirmed on presentation at TAH using serological HIV testing SB-649868 algorithms according to the South African national protocol (26). Infants received their vaccinations at public health clinics according to the then-applicable Expanded Program for Immunization (EPI). These included oral polio vaccine and.