Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates

Ishida, Elise; Corrigan, Devin T.; Chen, Tingting; Liu, Yanyan; Kim, Ryung S.; Song, Lusheng; Rutledge, Tara M.; Magee, D Mitchell; LaBaer, Joshua; Lowary, Todd L.; Lin, Philana Ling; Achkar, Jacqueline M.

doi:10.1016/j.ebiom.2023.104897

Cited by 3 publications

(1 citation statement)

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“…LAM detection in urine or sputum has been investigated as a potential diagnostic tool with some success ( 36 , 37 ). A recent study in a cynomolgus macaque model also showed that IgA to LAM was significantly reduced in animals with ATB compared to animals with LTBI ( 38 ). Furthermore, another study showed that children with disseminated TB had reduced LAM IgG compared to children with localized TB ( 39 ).…”

Section: Discussionmentioning

confidence: 96%

Impact of in-utero exposure to HIV and latent TB on infant humoral responses

Hjelmar,

de Armas,

Goldberg

et al. 2024

Front. Immunol.

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IntroductionLatent tuberculosis infection (LTBI) is a common coinfection in people living with HIV (PWH). How LTBI and HIV exposure in utero influence the development of infant humoral immunity is not well characterized. To address this question, we assessed the relationship between maternal humoral responses in pregnant women with HIV or with HIV/LTBI on humoral responses in infants to BCG vaccination and TB acquisition.MethodsPlasma samples were obtained from mother infant pairs during pregnancy (14-34 wks gestation) and in infants at 12 and 44 wks of age from the IMPAACT P1078 clinical trial. LTBI was established by Interferon gamma release assay (IGRA). Progression to active TB (ATB) disease was observed in 5 women at various times after giving birth. All infants were BCG vaccinated at birth and tested for IGRA at 44 weeks. Mtb (PPD, ESAT6/CFP10, Ag85A, LAM), HIV (GP120), and Influenza (HA) specific IgG, IgM, and IgA were measured in plasma samples using a bead based Luminex assay with Flexmap 3D.ResultsIn maternal plasma there were no differences in Mtb-specific antibodies or viral antibodies in relation to maternal IGRA status. ATB progressors showed increases in Mtb-specific antibodies at diagnosis compared to study entry. However, when compared to the non-progressors at entry, progressors had higher levels of Ag85A IgG and reduced ESAT6/CFP10 IgG and LAM IgG, IgM, and IgA1. All infants showed a decrease in IgG to viral antigens (HIV GP120 and HA) from 12 to 44 weeks attributed to waning of maternally transferred antibody titers. However, Mtb-specific (PPD, ESAT6/CFP10, Ag85A, and LAM) IgG and IgM increased from 12 to 44 weeks. HIV and HA IgG levels in maternal and 12-week infant plasma were highly correlated, and ESAT6/CFP10 IgG and LAM IgG showed a relationship between maternal and infant Abs. Finally, in the subset of infants that tested IGRA positive at 44 weeks, we observed a trend for lower LAM IgM compared to IGRA- infants at 44 weeks.DiscussionThe results from our study raise the possibility that antibodies to LAM are associated with protection from progression to ATB and support further research into the development of humoral immunity against TB through infection or vaccination.

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Section: Discussionmentioning

confidence: 96%

Impact of in-utero exposure to HIV and latent TB on infant humoral responses

Hjelmar,

de Armas,

Goldberg

et al. 2024

Front. Immunol.

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Optimizing antigen selection for the development of tuberculosis vaccines

Yang,

Chen,

Xia

2024

Cell Insight

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Antigen specificity shapes antibody functions in tuberculosis

Miles,

Lu,

Bai

et al. 2024

Preprint

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Tuberculosis (TB) is the number one infectious disease cause of death worldwide in part due to an incomplete understanding of immunity. Emerging data highlight antibody functions as correlates of protection and disease across human TB. However, little is known about how antibody functions impactMycobacterium tuberculosis (Mtb), the causative agent. Here, we use antigen specificity to understand how antibodies mediate host-Mtbinteractions. We focus onMtbcell wall and ESAT-6 & CFP-10, critical bacterial structural and secreted virulence proteins. In polyclonal IgG from TB patients, we observe that antigen specificity alters IgG subclass and glycosylation that drives Fc receptor binding and effector functions. Through in vitro models ofMtbmacrophage infection we find thatMtbcell wall IgG3, sialic acid, and fucose increase opsonophagocytosis of extracellularMtband bacterial burden, suggesting that some polyclonal IgG enhance disease. In contrast, ESAT-6 & CFP-10 IgG1 inhibits intracellularMtb, suggesting that antibodies targeting secreted virulence factors are protective. We test this hypothesis by generating a mAb that reacts to ESAT-6 & CFP-10 and show that it alone inhibits intracellularMtb. Understanding which antigens elicit antibody mediated disease enhancement and or protection will be critical in appreciating the many roles for antibodies in TB.

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Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates

Cited by 3 publications

References 79 publications

Impact of in-utero exposure to HIV and latent TB on infant humoral responses

Impact of in-utero exposure to HIV and latent TB on infant humoral responses

Optimizing antigen selection for the development of tuberculosis vaccines

Antigen specificity shapes antibody functions in tuberculosis

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