Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Abstract

e 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.

Incidence of Severe and Nonsevere Pertussis Among HIV-Exposed and -Unexposed Zambian Infants Through 14 Weeks of Age: Results From the Southern Africa Mother Infant Pertussis Study (SAMIPS), a Longitudinal Birth Cohort Study

“…Consistent with other studies, we observed a strong female to male predominance among the infants with pertussis [27]. Prior studies have been equivocal regarding the relationship between maternal HIV infection and pertussis [28, 29]. Here, maternal HIV appeared to modestly increase infant incidence, although it did not reach statistical significance.…”

Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants

“…Maternal HIV exposure did not appear to compromise infant responses to the primary Hib vaccine series, which were robust in all subjects, consistent with previous reports (35,36). Indeed, the vaccine responses in our study are typical of observations in non-HIV-exposed populations in developing countries, where initial Hib vaccine responses may be more vigorous than in higher-income populations (37), as observed in Nepal, South Africa, and Latin America, where 95 to 100% of the infants generate protective levels of Hib-specific IgG (Ͼ1 g/ml) after a primary series.…”

“…The first, the decrease in Hib IgG concentrations from 24 to 48 weeks of age, may lead to levels below the protective threshold in the ensuing months, consistent with previous findings in both HIV-exposed and -unexposed infants (35,38,43). Such data have been invoked in support of a recommendation for a booster dose at 1 year.…”

The seroprevalence ofBordetella pertussisantibodies in adolescents in the Western Cape

“…The question remains as to whether or not subsequent seropositivity against pertussis or any other pathogen equates to actual protection against the disease. 24,[28][29][30] The assay that was used in this study was unable to distinguish between IgG antibodies produced as a result of primary infection or vaccination. Furthermore, while PT is exclusively secreted by B. pertussis, FHA is also secreted by B. parapertussis and B. bronchiseptica.…”