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Article ; Online: Distinct N-Linked Immunoglobulin G Glycosylation Patterns Are Associated With Chronic Pathology and Asymptomatic Infections in Human Lymphatic Filariasis.

Adjobimey, Tomabu / Hoerauf, Achim

2022 Volume 13, Page(s) 790895

Abstract: Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. Emerging evidence suggests a link between the physiopathology ... ...

Abstract	Lymphatic filariasis presents a complex spectrum of clinical manifestations ranging from asymptomatic microfilariaemic (MF+) to chronic pathology (CP), including lymphedema and elephantiasis. Emerging evidence suggests a link between the physiopathology of filarial infections and antibody properties. Post-translational glycosylation has been shown to play a key role in the modulation of antibodies' effector functions. Here, we investigated the link between total IgG-N-glycosylation patterns and the physiopathology of human lymphatic filariasis using UPLC-FLD/ESI-MS comparison of N-glycan profiles of total IgG purified from endemic normals (EN), MF+, and CP patients. We detected a total of 19 glycans released from all IgG samples. Strikingly, agalactosylated glycan residues were more prominent in EN, whereas sialylation and bisecting GlcNac correlated with asymptomatic infections. While IgG from all three clinical groups expressed high levels of fucosylated residues, significantly lower expressions of afucosylated IgG were seen in MF+ individuals compared to EN and CP. Our data reveal distinct N-linked IgG glycan profiles in EN, MF+, and CP and suggest that IgG galactosylation and sialylation are associated with chronic pathology, whereas agalactosylation correlates with putative immunity. The results also indicate a role for sialylation, fucosylation, and bisecting GlcNac in immune tolerance to the parasite. These findings highlight the link between N-glycosylation and the physiopathology of lymphatic filariasis and open new research avenues for next-generation therapeutic formulations against infectious diseases.
MeSH term(s)	Asymptomatic Infections ; Elephantiasis, Filarial ; Glycosylation ; Humans ; Immunoglobulin G ; Polysaccharides
Chemical Substances	Immunoglobulin G ; Polysaccharides
Language	English
Publishing date	2022-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.790895
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Article ; Online: Helminth antigens differentially modulate the activation of CD4

Adjobimey, Tomabu / Meyer, Julia / Terkeš, Vedrana / Parcina, Marijo / Hoerauf, Achim

BMC medicine

2022 Volume 20, Issue 1, Page(s) 241

Abstract: Background: The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by SARS-CoV-2, a recently discovered strain of coronavirus. The virus has spread rapidly, causing millions of death worldwide. Contrary to the predictions, prevalence ... ...

Abstract	Background: The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by SARS-CoV-2, a recently discovered strain of coronavirus. The virus has spread rapidly, causing millions of death worldwide. Contrary to the predictions, prevalence and mortality due to COVID-19 have remained moderate on the African continent. Several factors, including age, genetics, vaccines, and co-infections, might impact the course of the pandemic in Africa. Helminths are highly endemic in Sub-Saharan Africa and are renowned for their ability to evade, skew, and suppress human immune responses through various immune-modulatory mechanisms. Such effects will likely impact SARS-CoV-2 transmission and disease progression. Methods: Here, we analyzed in vitro the impact of antigen extracts from three major helminth parasites, including Onchocerca volvulus, Brugia malayi, and Ascaris lumbricoides, on the immune reactivity to SARS-CoV-2 peptides in COVID-19 patients. Activation of CD4 Results: We observed that helminth antigens significantly reduced the frequency of SARS-CoV-2-reactive CD4 Conclusions: Our data offer a plausible explanation for the moderate incidence of COVID-19 in Africa and support the hypothesis that helper T cell-mediated immune responses to SARS-CoV-2 are mitigated in the presence of helminth antigens, while virus-specific cytotoxic T cell responses are maintained.
MeSH term(s)	Antigens, Helminth ; Benin ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; COVID-19 ; Humans ; Interleukin-10 ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha
Chemical Substances	Antigens, Helminth ; Tumor Necrosis Factor-alpha ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2022-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-022-02441-x
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Article ; Online: 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.

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 P / Hoerauf, Achim

Frontiers in tropical diseases

2024 Volume 4

Abstract: Filariae are vector borne parasitic nematodes, endemic in tropical and subtropical regions causing avoidable infections ranging from asymptomatic to stigmatizing and disfiguring disease. The filarial species that are the major focus of our institution's ... ...

Abstract	Filariae are vector borne parasitic nematodes, endemic in tropical and subtropical regions causing avoidable infections ranging from asymptomatic to stigmatizing and disfiguring disease. The filarial species that are the major focus of our institution's research are
Language	English
Publishing date	2024-04-24
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-7515
ISSN (online)	2673-7515
DOI	10.3389/fitd.2023.1126173
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Article ; Online: Helminth antigens differentially modulate the activation of CD4+ and CD8+ T lymphocytes of convalescent COVID-19 patients in vitro

Tomabu Adjobimey / Julia Meyer / Vedrana Terkeš / Marijo Parcina / Achim Hoerauf

BMC Medicine, Vol 20, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Background The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by SARS-CoV-2, a recently discovered strain of coronavirus. The virus has spread rapidly, causing millions of death worldwide. Contrary to the predictions, ... ...

Abstract	Abstract Background The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by SARS-CoV-2, a recently discovered strain of coronavirus. The virus has spread rapidly, causing millions of death worldwide. Contrary to the predictions, prevalence and mortality due to COVID-19 have remained moderate on the African continent. Several factors, including age, genetics, vaccines, and co-infections, might impact the course of the pandemic in Africa. Helminths are highly endemic in Sub-Saharan Africa and are renowned for their ability to evade, skew, and suppress human immune responses through various immune-modulatory mechanisms. Such effects will likely impact SARS-CoV-2 transmission and disease progression. Methods Here, we analyzed in vitro the impact of antigen extracts from three major helminth parasites, including Onchocerca volvulus, Brugia malayi, and Ascaris lumbricoides, on the immune reactivity to SARS-CoV-2 peptides in COVID-19 patients. Activation of CD4+ and CD8+ T cells was investigated using flow cytometry to monitor the expression of CD137 (4-1BB) and CD69. Cytokine expression, including IL-6, IL-10, IFN-γ, and TNFα, was measured by Luminex in cell culture supernatants. Results We observed that helminth antigens significantly reduced the frequency of SARS-CoV-2-reactive CD4+ T helper cells. In contrast, the expression of SARS-CoV-2-reactive CD8+ T cells was not affected and even significantly increased when PBMCs from COVID-19 patients living in Benin, an endemic helminth country, were used. In addition, stimulation with helminth antigens was associated with increased IL-10 and a reduction of IFNγ and TNFα. Conclusions Our data offer a plausible explanation for the moderate incidence of COVID-19 in Africa and support the hypothesis that helper T cell-mediated immune responses to SARS-CoV-2 are mitigated in the presence of helminth antigens, while virus-specific cytotoxic T cell responses are maintained.
Keywords	COVID-19 ; SARS-CoV-2 ; Helminth antigens ; CD4+ helper and CD8+ T cytotoxic T cells ; activation markers ; CD137 (4-1BB) ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article: Characteristics of

Sina, Haziz / Dah-Nouvlessounon, Durand / Adjobimey, Tomabu / Boya, Bawa / Dohoue, Ghislaine M C / N'tcha, Christine / Chidikofan, Violette / Baba-Moussa, Farid / Abdoulaye, Idrissou / Adjanohoun, Adolphe / Baba-Moussa, Lamine

Journal of pathogens

2022 Volume 2022, Page(s) 6253894

Abstract: Escherichia ... ...

Abstract	Escherichia coli
Language	English
Publishing date	2022-06-06
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2662334-1
ISSN	2090-3065 ; 2090-3057
ISSN (online)	2090-3065
ISSN	2090-3057
DOI	10.1155/2022/6253894
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Article ; Online: IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism.

Prodjinotho, Ulrich F / Hoerauf, Achim / Adjobimey, Tomabu

Parasitology research

2019 Volume 118, Issue 10, Page(s) 2957–2968

Abstract: A striking feature of lymphatic filariasis (LF) is the clinical heterogeneity among exposed individuals. While endemic normals (EN) remain free of infection despite constant exposure to the infective larvae, a small group of patients, generally ... ...

Abstract	A striking feature of lymphatic filariasis (LF) is the clinical heterogeneity among exposed individuals. While endemic normals (EN) remain free of infection despite constant exposure to the infective larvae, a small group of patients, generally microfilaria free (Mf-) develops severe pathology (CP) such as lymphedema or hydrocele. Another group of infected individuals remains asymptomatic while expressing large amounts of microfilariae (Mf+). This Mf+ group is characterized by an immune-suppressed profile with high levels of anti-inflammatory cytokines and elevated IgG4. This particular immunoglobulin is unable to activate the complement. The complement system plays a critical role in both innate and adaptive immunity. However, its importance and regulation during LF is not fully understood. Using affinity chromatography and solid-phase-enzyme-immunoassays, we investigated the ability of antibody isotypes from LF clinical groups to bind C1q, the first element of the complement's classical pathway. The results indicate that while C1q is similarly expressed in all LF clinical groups, IgG1-2 in the plasma from Mf+ individuals presented significantly lower affinity to C1q compared to EN, Mf-, and CP. In addition, selective depletion of IgG4 significantly enhanced the affinity of IgG1-2 to C1q in Mf+ individuals. Strikingly, no effect was seen on the ability of IgG3 to bind C1q in the same conditions. More interestingly, papain-generated IgG4-Fc-portions interacted with Fc portions of IgG1-2 as revealed by far-western blot analysis. These data suggest that while being unable to bind C1q, IgG4 inhibits the first steps of the complement classical pathway by IgG1 or IgG2 via Fc-Fc interactions.
MeSH term(s)	Adult ; Animals ; Complement C1q/immunology ; Complement Pathway, Classical ; Elephantiasis, Filarial/immunology ; Humans ; Immunoglobulin Fc Fragments/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/classification ; Immunoglobulin G/immunology ; Male ; Microfilariae/immunology ; Middle Aged ; Young Adult
Chemical Substances	Immunoglobulin Fc Fragments ; Immunoglobulin G ; Complement C1q (80295-33-6)
Language	English
Publishing date	2019-09-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-019-06451-2
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Article ; Online: In vivo

Konmy, Basile / Olounladé, Pascal Abiodoun / Adjobimey, Tomabu / Dansou, Christian Cocou / Adoho, Akouavi Carine Chimène / Tchetan, Esaïe / Alowanou, Georcelin Goué / Azando, Erick Virgile Bertrand / Adjanohoun, Adolphe / Doko Allou, Sanni-Yo / Baba-Moussa, Lamine

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1173138

Abstract: Introduction: The aims of this study were to determine the immune response and the anticoccidial activity induced by : Methods: Thirty-five-day-old rabbits, free from coccidia, were infested with 2.10: Results and discussion: The inhibition of the ...

Abstract	Introduction: The aims of this study were to determine the immune response and the anticoccidial activity induced by Methods: Thirty-five-day-old rabbits, free from coccidia, were infested with 2.10 Results and discussion: The inhibition of the excretion of oocysts was evaluated by the McMaster technique and the levels of cytokines (IL-4 and IL-12) and immunoglobulin IgG were assayed by the ELISA method. The
MeSH term(s)	Animals ; Rabbits ; Eimeria ; Vernonia ; Moringa oleifera ; Acetone ; Interleukin-4 ; Plant Extracts/pharmacology ; Immunoglobulin G ; Interleukin-12 ; Immunity
Chemical Substances	Acetone (1364PS73AF) ; Interleukin-4 (207137-56-2) ; Plant Extracts ; Immunoglobulin G ; Interleukin-12 (187348-17-0)
Language	English
Publishing date	2023-05-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1173138
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Article ; Online: 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.

Adjobimey, Tomabu / Meyer, Julia / Sollberg, Leander / Bawolt, Michael / Berens, Christina / Kovačević, Peđa / Trudić, Anika / Parcina, Marijo / Hoerauf, Achim

Frontiers in immunology

2022 Volume 13, Page(s) 917905

Abstract: In an ongoing multinational trial, we obtained blood samples from 365 volunteers vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from ... ...

Abstract	In an ongoing multinational trial, we obtained blood samples from 365 volunteers vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from Sinopharm. After collecting reactogenicity data, the expression of S-Protein binding IgG and IgA was analyzed using an automated sandwich ELISA system. Serum neutralizing potentials were then investigated using an ACE-2-RBD neutralizing assay. Moderna's vaccine induced the highest amounts of SARS-CoV-2 specific neutralizing antibodies compared to the other groups. In contrast, Sinopharm and Johnson and Johnson's vaccinees presented the lowest SARS-CoV-2-specific antibody titers. Interestingly, moderate to high negative correlations between age and virus-specific IgG expression were observed in the Johnson and Johnson (ρ =-0.3936) and Sinopharm (ρ =-0.6977) groups according to Spearman's rank correlation analysis. A negative correlation was seen between age and IgA expression in the Sputnik-V group (ρ =-0.3917). The analysis of virus neutralization potentials in age categories demonstrated that no significant neutralization potential was observed in older vaccinees (61and 80 years old) in the Sputnik-V Johnson and Johnson and Sinopharm vaccinees' groups. In contrast, neutralization potentials in sera of Moderna, BioNTech, and AstraZeneca vaccinees were statistically comparable in all age categories. Furthermore, while the AstraZeneca vaccine alone induced moderate IgG and IgA expression, the combination with Moderna or BioNTech mRNA vaccines induced significantly higher antibody levels than a double dose of AstraZeneca and similar IgG expression and neutralization potential compared to Moderna or BioNTech vaccines used alone. These results suggest that mRNA vaccines are the most immunogenic after two doses. DNA vectored vaccines from AstraZeneca and Sputnik-V presented lower but significant antibody expression and virus neutralizing properties after two doses. The lowest antibody and neutralization potential were observed in the Sinopharm or Johnson and Johnson vaccinees. Especially elderly over 60 presented no significant increase in neutralizing antibodies after vaccination. The data also indicate that heterologous vaccination strategies combining the AstraZeneca DNA vectored vaccines and mRNA vaccines are more effective in the induction of neutralizing antibodies compared to their homologous counterparts.
MeSH term(s)	Aged ; Aged, 80 and over ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; DNA ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Neutralization Tests ; SARS-CoV-2 ; Vaccination ; Vaccines, Attenuated ; Vaccines, DNA
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin A ; Immunoglobulin G ; Vaccines, Attenuated ; Vaccines, DNA ; DNA (9007-49-2)
Language	English
Publishing date	2022-06-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.917905
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Article: Susceptibility and Virulence of

Assouma, Funkè F / Sina, Haziz / Adjobimey, Tomabu / Noumavo, Agossou Damien Pacôme / Socohou, Akim / Boya, Bawa / Dossou, Ange D / Akpovo, Lauriane / Konmy, Basile Boni Saka / Mavoungou, Jacques F / Adjanohoun, Adolphe / Baba-Moussa, Lamine

Microorganisms

2023 Volume 11, Issue 1

Abstract: Enterobacteriaceae represent one of the main families of Gram-negative bacilli responsible for serious urinary tract infections (UTIs). The present study aimed to define the resistance profile and the virulence of Enterobacteriaceae strains isolated in ... ...

Abstract	Enterobacteriaceae represent one of the main families of Gram-negative bacilli responsible for serious urinary tract infections (UTIs). The present study aimed to define the resistance profile and the virulence of Enterobacteriaceae strains isolated in urinary tract infections in Benin. A total of 390 urine samples were collected from patients with UTIs, and Enterobacteriaceae strains were isolated according to standard microbiology methods. The API 20E gallery was used for biochemical identification. All the isolated strains were subjected to antimicrobial susceptibility testing using the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was investigated using a double-disc synergy test (DDST), and biofilm production was quantified using the microplate method. Multiplex PCR was used to detect uro-virulence genes, namely: PapG, IronB, Sfa, iucD, Hly, FocG, Sat, FyuA and Cnf, using commercially designed primers. More than 26% (103/390) of our samples were contaminated by Enterobacteriaceae strains at different levels. Thus, E. coli (31.07%, 32/103), Serratia marcescens (11.65%, 12/103), Klebsiella ornithinolytica (8.74%, 9/103), Serratia fonticola (7.77%, 8/103) and Enterobacter cloacae (6.80%, 7/103) were identified. Among the isolated strains, 39.81% (41/103) were biofilm-forming, while 5.83% (6/103) were ESBL-producing. Isolates were most resistant to erythromycin, cefixime, ceftriaxone and ampicillin (≥90%) followed by ciprofloxacin, gentamycin, doxycycline and levofloxacin (≥50%), and least resistant to imipenem (27.18%). In regard to virulence genes, Sfa was the most detected (28.15%), followed by IronB (22.23%), iucD (21.36%), Cnf (15.53%), PapG (9.71%), FocG (8.74%), Sat (6.79%), FyuA (5.82%) and Hyl (2.91%). These data may help improve the diagnosis of uropathogenic strains of Enterobacteriaceae, but also in designing effective strategies and measures for the prevention and management of severe, recurrent, or complicated urinary tract infections in Benin.
Language	English
Publishing date	2023-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11010213
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Article ; Online: Negative association between ascaris lumbricoides seropositivity and Covid-19 severity: insights from a study in Benin.

Adjobimey, Tomabu / Meyer, Julia / Hennenfent, Anneka / Bara, Anick J / Lagnika, Latifou / Kocou, Bienvenu / Adjagba, Marius / Laleye, Anatole / Hoerauf, Achim / Parcina, Marijo

Frontiers in immunology

2023 Volume 14, Page(s) 1233082

Abstract: Introduction: The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris ... ...

Abstract	Introduction: The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions. Methods: The present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression. Results and discussion: The results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milder COVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies.
MeSH term(s)	Humans ; Animals ; Ascaris lumbricoides ; Benin/epidemiology ; COVID-19/epidemiology ; Diabetes Mellitus, Type 2 ; Pandemics ; SARS-CoV-2 ; Ascaris ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-08-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1233082
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