HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of
infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from
infection. The possibility exists that altered response to vaccination contributes to the higher rate of
infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following the WHO extended program on immunization (EPI).
Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total
IgG and
antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib),
tetanus toxoid, hepatitis B virus (
HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine
antibodies (maternal
antibodies passively acquired) specific for
tetanus were lower in HEU than in HUU infants, while prevaccine
antibodies to
HepB were higher in HEU than in HUU infants. Both groups responded similarly to
tetanus, Hib, and
HepB vaccination. HEU demonstrated stronger
pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and 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.