Abstract
It is unclear whether antibodies can prevent Mycobacterium tuberculosis (Mtb) infection. In this study, we examined the relationship between total plasma IgG levels, IgG elicited by childhood vaccines and soil-transmitted helminths, and Mtb infection prevalence, defined by positive QuantiFERON (QFT) test. We studied 100 Mtb uninfected infants, aged 4-6 months. Ten infants (10%) converted to positive QFT test (QFT+) within 2 years of follow-up for Mtb infection. Antibody responses in plasma samples acquired at baseline and tuberculosis investigation were analyzed by enzyme-linked immunosorbent assay and ImmunoCAP® assay. QFT- infants displayed a significant increase in total IgG titers when re-tested, compared to IgG titers at baseline, which was not observed in QFT+ infants. Bacille Calmette-Guérin (BCG) vaccine-specific IgG2 and live-attenuated measles vaccine-specific IgG were raised in QFT- infants, and infants who acquired an Mtb infection did not appear to launch a BCG-specific IgG2 response. IgG titers against the endemic helminth Ascaris lumbricoides increased from baseline to QFT re-testing in all infants. These data show raised IgG associates with a QFT-status. Importantly, this effect was also associated with a trend showing raised IgG titers to BCG and measles vaccine. Our data suggest a possible protective association between raised antibody titers and acquisition of Mtb infection, potentially mediated by exposure to antigens both related and unrelated to Mtb.
Highlights
Mycobacterium tuberculosis (Mtb) infection and tuberculosis (TB) disease represents one of the greatest global infectious disease burdens [1]
Since helminth exposure can alter risk and outcome of Mtb disease [29,30,31], we examined if any relationship existed between infant exposure to A. lumbricoides and Mtb infection
We found that infants who did not acquire Mtb infection had significantly increased total IgG titers from baseline to TB investigation, unlike infants who became Mtb infected
Summary
Mycobacterium tuberculosis (Mtb) infection and tuberculosis (TB) disease represents one of the greatest global infectious disease burdens [1]. The only licensed TB vaccine, Bacille Calmette-Guérin (BCG), may partially protect against Mtb infection and provides protection against disseminated forms of active TB disease [2,3,4,5], but protection against pulmonary TB disease varies widely with age and mycobacterial exposure [6]. Development of a vaccine that is more effective than BCG is crucial for the ultimate control of both Mtb infection and TB disease [7, 8]. There is no clinical evidence to support the hypothesis that an effective TB vaccine might be based on induction of an antibody response that controls Mtb infection. It is unclear whether antibodies can prevent Mycobacterium tuberculosis (Mtb) infection. We examined the relationship between total plasma IgG levels, IgG elicited by childhood vaccines and soil-transmitted helminths, and Mtb infection prevalence, defined by positive QuantiFERON (QFT) test
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