Determination of molecular mechanisms supporting the anti-inflammatory properties of IgG4 antibodies in filarial infected individuals
Immunology
Final Report Abstract
Our project initially aimed to understand the molecular mechanisms behind the antiinflammatory properties of immunoglobulin (IgG)4 antibodies in individuals with filarial infections. Through a series of experiments, including solid-state immunoassays and coimmunoprecipitation, we explored the immune-regulating functions of IgG4 antibodies and their interactions with other antibody subclasses. Our investigations revealed a significant decrease in complement (C1q) binding potential of pro-inflammatory IgG subclasses (IgG1 and IgG2) when they are in contact with IgG4-Fc. This suggested a possible mechanism through which IgG4 antibodies mitigate the inflammatory properties of other antibodies. A significant part of our study was the examination of antibody N-glycosylation patterns using liquid chromatography-mass spectrometry (LC-MS). We observed marked differences in IgG N-glycan heterogeneity among various lymphatic filariasis (LF) patient groups. Specific glycan residues, such as sialyl- and bisecting GlcNac-, correlated with asymptomatic microfilaremia, a condition often associated with high IgG4 expression. This crucial finding emphasized the potentially influential role of IgG N-glycosylation patterns in filarial infections. The onset of the COVID-19 pandemic prompted us to broaden our research scope to examine the interplay between helminth-induced immunoregulatory mechanisms described in our previous studies on the immunological susceptibility to SARS-CoV-2. Our observations indicated that helminth antigens could modulate the immune response to SARS-CoV-2 by inhibiting the activation of SARS-CoV-2-reactive helper T cells while promoting the activation of cytotoxic T cells. We were also among the first groups to report that mRNA COVID-19 vaccines, specifically Pfizer-BioNTech's Comirnaty (BNT162b2) and Moderna's Spikevax (mRNA-1273), elicited more robust antibody responses compared to other types of COVID- 19 vaccines. Importantly, our data also suggest that concurrent helminth infections, identified by Ascaris antibody expression or circulating filaria antigens (CFA), did not affect antibody responses to COVID-19 vaccines. At the same time, they significantly reduced antibody responses in SARS-CoV-2-infected individuals. Our findings have revealed two mechanisms, including the modulation of complement activation, and altered glycosylation patterns, that could explain the immunomodulatory functions of IgG4. These results have been published in four peer-reviewed articles in relevant scientific journals and contribute to a broader understanding of immune responses during helminth and COVID-19 infections. They provide invaluable insights that can guide the development of therapeutic strategies and inform public health policy in combating infectious diseases.
Publications
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IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism. Parasitology Research, 118(10), 2957-2968.
Prodjinotho, Ulrich F.; Hoerauf, Achim & Adjobimey, Tomabu
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Comparison of IgA, IgG, and Neutralizing Antibody Responses Following Immunization With Moderna, BioNTech, AstraZeneca, Sputnik-V, Johnson and Johnson, and Sinopharm’s COVID-19 Vaccines. Frontiers in Immunology, 13.
Adjobimey, Tomabu; Meyer, Julia; Sollberg, Leander; Bawolt, Michael; Berens, Christina; Kovačević, Peđa; Trudić, Anika; Parcina, Marijo & Hoerauf, Achim
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Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis. Frontiers in Immunology, 13.
Adjobimey, Tomabu & Hoerauf, Achim
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Helminth antigens differentially modulate the activation of CD4+ and CD8+ T lymphocytes of convalescent COVID-19 patients in vitro. BMC Medicine, 20(1).
Adjobimey, Tomabu; Meyer, Julia; Terkeš, Vedrana; Parcina, Marijo & Hoerauf, Achim
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Filariasis research – from basic research to drug development and novel diagnostics, over a decade of research at the Institute for Medical Microbiology, Immunology and Parasitology, Bonn, Germany. Frontiers in Tropical Diseases, 4.
Karunakaran, Indulekha; Ritter, Manuel; Pfarr, Kenneth; Klarmann-Schulz, Ute; Debrah, Alexander Yaw; Debrah, Linda Batsa; Katawa, Gnatoulma; Wanji, Samuel; Specht, Sabine; Adjobimey, Tomabu; Hübner, Marc Peter & Hoerauf, Achim
