Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response

Abstract

Background-In most tuberculosis (TB) endemic countries, bacillus Calmette Guérin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response.

CD4 and CD8 T-Cell Responses to Mycobacterial Antigens in African Children

“…We report here that the Ag85B/TB10.4-specific T-cell response was characterized by an effector memory phenotype. This is in agreement with memory phenotypes reported previously on mycobacteriaspecific T cells in adults (54), children (55), and infants (44,45). Both presence and absence of the differentiation marker, CD27, was observed on these effector memory CD4 and CD8 T cells, suggesting an intermediate to an advanced stage of differentiation.…”

“…Along these lines, a considerable proportion of mycobacteriaspecific T cells express Th1 cytokines, but show a ''naive'' CD45RA 1 CCR7 1 phenotype. Such T-cell phenotypes have previously been reported in other studies of antimycobacterial T cells by us and others (44,45,54,56). We previously suggested that this CD45RA 1 CCR7 1 population reflects early differentiation into Ag-specific cells, before losing CD45RA expression (44).…”

“…To date, few data are available on the character of T-cell responses in older children, who are more likely to have been exposed to TB. Most studies in children have been performed after BCG vaccination in infants (44)(45)(46). These studies report lower frequencies of specific CD4 and also CD8 T cells in infants to those observed here in older children.…”

Control of Chronic Mycobacterium tuberculosis Infection by CD4 KLRG1− IL-2–Secreting Central Memory Cells

“…Data from infected individuals provide the same overall interpretation with progressive impairment of M. tuberculosisspecific CD4 T cell responses with increasing mycobacterial load (24)(25)(26), a development that could be abrogated by anti-TB treatment (24). Whereas various cross-sectional studies in children have shown that BCG primarily promotes effector/effector memory T cells (similar to the real TB infection) (27,28), a recent longitudinal study in infants has documented a more complex pattern, with BCG-specific CD4 T cells displaying characteristics of both central and effector memory T cells (29). In mice models, we have previously reported that adoptive transfer of M. tuberculosis-specific memory cells (from cleared infection or after subunit vaccination) can confer significant protection to challenge (30,31), and that central memory T cells (T CM ) are the most important subset responsible for this effect (30).…”

Current status of new tuberculosis vaccine in children

“…89 In addition to HIV-infected infants, a recent study by Kagina et al demonstrated that delaying BCG vaccination from birth to 10 weeks of age in HIV-unexposed infants resulted in higher frequencies of BCG-specific, polyfunctional CD4 T cells at 1 y of age. 90 In contrast, Burl and his colleagues found that delaying BCG vaccination from birth to 18 weeks of age led to decreased IFN-g and IL-17 production in the delayed vaccinated group. 91 They hypothesized that the decrease might be attributed to the exposure to NTM prior to BCG vaccination, conferring the induction of Tregs, which would reduce the immune response to BCG vaccination.…”