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Prof. Dr. Martin Bachmann
Department of Immunology, University of Bern, 3012 Bern, Switzerland

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0 Allergy
0 Immunology
0 Infectious Diseases
0 Vaccines
0 Antibody

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Original article
Published: 08 July 2021 in Allergy
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Background Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor-binding domain (RBD) of the spike protein. It is unclear which mutations affect receptor affinity versus immune recognition. Methods We produced wild type RBD, RBD with single mutations (E484K, K417N, or N501Y) or with all three mutations combined and tested their binding to ACE2 by biolayer interferometry (BLI). The ability of convalescent sera to recognize RBDs and block their interaction with ACE2 was tested as well. Results We demonstrated that single mutation N501Y increased binding affinity to ACE2 but did not strongly affect its recognition by convalescent sera. In contrast, single mutation E484K had almost no impact on the binding kinetics, but essentially abolished recognition of RBD by convalescent sera. Interestingly, combining mutations E484K, K417N, and N501Y resulted in a RBD with both features: enhanced receptor binding and abolished immune recognition. Conclusions Our data demonstrate that single mutations either affect receptor affinity or immune recognition while triple mutant RBDs combine both features.

ACS Style

Monique Vogel; Gilles Sousa Augusto; Xinyue Chang; Xuelan Liu; Daniel Speiser; Mona O. Mohsen; Martin F. Bachmann. Molecular definition of SARS‐CoV‐2 RBD mutations: receptor affinity versus neutralization of receptor interaction. Allergy 2021, 1 .

AMA Style

Monique Vogel, Gilles Sousa Augusto, Xinyue Chang, Xuelan Liu, Daniel Speiser, Mona O. Mohsen, Martin F. Bachmann. Molecular definition of SARS‐CoV‐2 RBD mutations: receptor affinity versus neutralization of receptor interaction. Allergy. 2021; ():1.

Chicago/Turabian Style

Monique Vogel; Gilles Sousa Augusto; Xinyue Chang; Xuelan Liu; Daniel Speiser; Mona O. Mohsen; Martin F. Bachmann. 2021. "Molecular definition of SARS‐CoV‐2 RBD mutations: receptor affinity versus neutralization of receptor interaction." Allergy , no. : 1.

Journal article
Published: 11 June 2021 in Vaccines
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The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm and 200 nm silica nanoparticles (SiNPs) to optimize conjugation density and attachment stability. Env was redesigned to enable site-specific cysteine-mediated covalent conjugation while maintaining its structural integrity and antigenicity. Env was anchored to different sized SiNPs with a calculated spacing of 15 nm between adjacent trimers. Both particle sizes exhibited high in vitro stability over a seven-day period. After attachment, 100 nm particles showed better colloidal stability compared to 200 nm particles. Importantly, the antigenic profile of Env was not impaired by surface attachment, indicating that the quaternary structure was maintained. In vitro Env uptake by dendritic cells was significantly enhanced when Env was delivered on the surface of nanoparticles compared to soluble Env. Furthermore, multivalent Env displayed efficiently activated B cells even at Env concentrations in the low nanomolar range. In mice, antibody responses to nanoparticle-coupled Env were stronger compared to the free protein and had equivalent effects at lower doses and without adjuvant.

ACS Style

David Peterhoff; Stefanie Thalhauser; Jan Sobczak; Mona Mohsen; Christoph Voigt; Nicole Seifert; Patrick Neckermann; Alexandra Hauser; Song Ding; Quentin Sattentau; Martin Bachmann; Miriam Breunig; Ralf Wagner. Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery. Vaccines 2021, 9, 642 .

AMA Style

David Peterhoff, Stefanie Thalhauser, Jan Sobczak, Mona Mohsen, Christoph Voigt, Nicole Seifert, Patrick Neckermann, Alexandra Hauser, Song Ding, Quentin Sattentau, Martin Bachmann, Miriam Breunig, Ralf Wagner. Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery. Vaccines. 2021; 9 (6):642.

Chicago/Turabian Style

David Peterhoff; Stefanie Thalhauser; Jan Sobczak; Mona Mohsen; Christoph Voigt; Nicole Seifert; Patrick Neckermann; Alexandra Hauser; Song Ding; Quentin Sattentau; Martin Bachmann; Miriam Breunig; Ralf Wagner. 2021. "Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery." Vaccines 9, no. 6: 642.

Letter to the editor
Published: 05 May 2021 in Allergy
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ACS Style

Xinyue Chang; Gilles Sousa Augusto; Xuelan Liu; Thomas M. Kündig; Monique Vogel; Mona O. Mohsen; Martin F. Bachmann. BNT162b2 mRNA COVID‐19 vaccine induces antibodies of broader cross‐reactivity than natural infection, but recognition of mutant viruses is up to 10‐fold reduced. Allergy 2021, 1 .

AMA Style

Xinyue Chang, Gilles Sousa Augusto, Xuelan Liu, Thomas M. Kündig, Monique Vogel, Mona O. Mohsen, Martin F. Bachmann. BNT162b2 mRNA COVID‐19 vaccine induces antibodies of broader cross‐reactivity than natural infection, but recognition of mutant viruses is up to 10‐fold reduced. Allergy. 2021; ():1.

Chicago/Turabian Style

Xinyue Chang; Gilles Sousa Augusto; Xuelan Liu; Thomas M. Kündig; Monique Vogel; Mona O. Mohsen; Martin F. Bachmann. 2021. "BNT162b2 mRNA COVID‐19 vaccine induces antibodies of broader cross‐reactivity than natural infection, but recognition of mutant viruses is up to 10‐fold reduced." Allergy , no. : 1.

Review
Published: 27 April 2021 in International Journal of Molecular Sciences
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Iron is a critical metal for several vital biological processes. Most of the body’s iron is bound to hemoglobin in erythrocytes. Iron from senescent red blood cells is recycled by macrophages in the spleen, liver and bone marrow. Dietary iron is taken up by the divalent metal transporter 1 (DMT1) in enterocytes and transported to portal blood via ferroportin (FPN), where it is bound to transferrin and taken up by hepatocytes, macrophages and bone marrow cells via transferrin receptor 1 (TfR1). While most of the physiologically active iron is bound hemoglobin, the major storage of most iron occurs in the liver in a ferritin-bound fashion. In response to an increased iron load, hepatocytes secrete the peptide hormone hepcidin, which binds to and induces internalization and degradation of the iron transporter FPN, thus controlling the amount of iron released from the cells into the blood. This review summarizes the key mechanisms and players involved in cellular and systemic iron regulation.

ACS Style

Anne-Cathrine Vogt; Tasneem Arsiwala; Mona Mohsen; Monique Vogel; Vania Manolova; Martin Bachmann. On Iron Metabolism and Its Regulation. International Journal of Molecular Sciences 2021, 22, 4591 .

AMA Style

Anne-Cathrine Vogt, Tasneem Arsiwala, Mona Mohsen, Monique Vogel, Vania Manolova, Martin Bachmann. On Iron Metabolism and Its Regulation. International Journal of Molecular Sciences. 2021; 22 (9):4591.

Chicago/Turabian Style

Anne-Cathrine Vogt; Tasneem Arsiwala; Mona Mohsen; Monique Vogel; Vania Manolova; Martin Bachmann. 2021. "On Iron Metabolism and Its Regulation." International Journal of Molecular Sciences 22, no. 9: 4591.

Journal article
Published: 19 April 2021 in Vaccines
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COVID-19 is a novel disease caused by SARS-CoV-2 which has conquered the world rapidly resulting in a pandemic that massively impacts our health, social activities, and economy. It is likely that vaccination is the only way to form “herd immunity” and restore the world to normal. Here we developed a vaccine candidate for COVID-19 based on the virus-like particle AP205 displaying the spike receptor binding motif (RBM), which is the major target of neutralizing antibodies in convalescent patients. To this end, we genetically fused the RBM domain of SARS-CoV-2 to the C terminus of AP205 of dimerized capsid proteins. The fused VLPs were expressed in E. coli, which resulted in insoluble aggregates. These aggregates were denatured in 8 M urea followed by refolding, which reconstituted VLP formation as confirmed by electron microscopy analysis. Importantly, immunized mice were able to generate high levels of IgG antibodies recognizing eukaryotically expressed receptor binding domain (RBD) as well as spike protein of SARS-CoV-2. Furthermore, induced antibodies were able to neutralize SARS-CoV-2/ABS/NL20. Additionally, this vaccine candidate has the potential to be produced at large scale for immunization programs.

ACS Style

Xuelan Liu; Xinyue Chang; Dominik Rothen; Mariliza Derveni; Pascal Krenger; Salony Roongta; Edward Wright; Monique Vogel; Kaspars Tars; Mona Mohsen; Martin Bachmann. AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate. Vaccines 2021, 9, 403 .

AMA Style

Xuelan Liu, Xinyue Chang, Dominik Rothen, Mariliza Derveni, Pascal Krenger, Salony Roongta, Edward Wright, Monique Vogel, Kaspars Tars, Mona Mohsen, Martin Bachmann. AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate. Vaccines. 2021; 9 (4):403.

Chicago/Turabian Style

Xuelan Liu; Xinyue Chang; Dominik Rothen; Mariliza Derveni; Pascal Krenger; Salony Roongta; Edward Wright; Monique Vogel; Kaspars Tars; Mona Mohsen; Martin Bachmann. 2021. "AP205 VLPs Based on Dimerized Capsid Proteins Accommodate RBM Domain of SARS-CoV-2 and Serve as an Attractive Vaccine Candidate." Vaccines 9, no. 4: 403.

Original article
Published: 18 April 2021 in Allergy
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Background Allergy is a global disease with overall frequencies of >20%. Symptoms vary from irritating local itching to life‐threatening systemic anaphylaxis. Even though allergies are allergen‐specific, there is a wide range of cross‐reactivities (e.g. apple and latex) that remain largely unexplained. Given the abilities of low affinity IgG antibodies to inhibit mast cells activation, here we elucidate the minimal affinity of IgE antibodies to induce type I hypersensitivity. Methods Three mature (high affinity) IgE antibodies recognizing three distinct epitopes on Fel d 1, the major cat allergen, were back‐mutated to germline conformation, resulting in binding to Fel d 1 with low affinity. The ability of theseIgEantibodies to activate mast cells in vitro and in vivo was tested. Results We demonstrate that affinities as low as 10‐7 M are sufficient to activate mast cells in vitro and drive allergic reactions in vivo. Low affinity IgE antibodies are able to do so, since they bind allergens bivalently on the surface of mast cells, leading to high‐avidity interactions. Conclusions These results suggest that the underlying mechanism of allergen‐cross‐reactivity may be low‐affinity but high‐avidity binding between IgE antibodies and cross‐reactive allergen.

ACS Style

Xinyue Chang; Lisha Zha; Alexandra Wallimann; Mona O. Mohsen; Pascal Krenger; Xuelan Liu; Monique Vogel; Martin F. Bachmann. Low‐affinity but high‐avidity interactions may offer an explanation for IgE‐mediated allergen cross‐reactivity. Allergy 2021, 76, 2565 -2574.

AMA Style

Xinyue Chang, Lisha Zha, Alexandra Wallimann, Mona O. Mohsen, Pascal Krenger, Xuelan Liu, Monique Vogel, Martin F. Bachmann. Low‐affinity but high‐avidity interactions may offer an explanation for IgE‐mediated allergen cross‐reactivity. Allergy. 2021; 76 (8):2565-2574.

Chicago/Turabian Style

Xinyue Chang; Lisha Zha; Alexandra Wallimann; Mona O. Mohsen; Pascal Krenger; Xuelan Liu; Monique Vogel; Martin F. Bachmann. 2021. "Low‐affinity but high‐avidity interactions may offer an explanation for IgE‐mediated allergen cross‐reactivity." Allergy 76, no. 8: 2565-2574.

Journal article
Published: 16 April 2021 in Vaccines
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The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMVTT). The RBD displayed CuMVTT bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMVTT resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro.

ACS Style

Lisha Zha; Xinyue Chang; Hongxin Zhao; Mona Mohsen; Liang Hong; Yuhang Zhou; Hongquan Chen; Xuelan Liu; Jie Zhang; Dong Li; Ke Wu; Byron Martina; Junfeng Wang; Monique Vogel; Martin Bachmann. Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles. Vaccines 2021, 9, 395 .

AMA Style

Lisha Zha, Xinyue Chang, Hongxin Zhao, Mona Mohsen, Liang Hong, Yuhang Zhou, Hongquan Chen, Xuelan Liu, Jie Zhang, Dong Li, Ke Wu, Byron Martina, Junfeng Wang, Monique Vogel, Martin Bachmann. Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles. Vaccines. 2021; 9 (4):395.

Chicago/Turabian Style

Lisha Zha; Xinyue Chang; Hongxin Zhao; Mona Mohsen; Liang Hong; Yuhang Zhou; Hongquan Chen; Xuelan Liu; Jie Zhang; Dong Li; Ke Wu; Byron Martina; Junfeng Wang; Monique Vogel; Martin Bachmann. 2021. "Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles." Vaccines 9, no. 4: 395.

Preprint content
Published: 15 March 2021
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Background: Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein. Objective: We aimed to assess how mutations in RBD affected recognition of immune sera by antibodies induced by natural infection versus immunization with BNT162b2, a mRNA- based vaccine against COVID-19. Methods: We produced SARS-CoV-2 RBD mutants with single mutations in the receptor binding domain (RBD) region (E484K, K417N, N501Y) or with all 3 mutations combined, as occurring in the newly emerged variants B.1.351 (South Africa) and P.1 (Brazil). Using standard and avidity ELISAs, we determined the binding capacities to mutant RBDs of antibodies induced by infection versus vaccination. Results: These binding assays showed that vaccination induced antibodies recognize both wildtype and mutant RBDs with higher avidities than those raised by infection. Nevertheless, recognition of mutants RBDK417N and RBDN501Y was 2.5-3-fold reduced while RBDE484K and the triple mutant were 10-fold less well recognized, demonstrating that the mutation at position 484 was key for the observed loss in cross-reactivity. Conclusion: Our binding data demonstrate improved recognition of mutant viruses by BNT162b2-induced antibodies compared to those induced by natural infection. Recognition may, however, be 10-fold reduced for the variants B.1.351/P.1, suggesting that the development of a new vaccine is warranted. The E484K mutation is an key hurdle for immune recognition, convalescent plasma and monoclonal antibody therapy as well as serological assays based on the wildtype sequence may therefore seriously impaired.

ACS Style

Mona O. Mohsen; Martin F. Bachmann; Monique Vogel; Gilles Sousa Augusto; Xuelan Liu; Xinyue Chang. BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced. 2021, 1 .

AMA Style

Mona O. Mohsen, Martin F. Bachmann, Monique Vogel, Gilles Sousa Augusto, Xuelan Liu, Xinyue Chang. BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced. . 2021; ():1.

Chicago/Turabian Style

Mona O. Mohsen; Martin F. Bachmann; Monique Vogel; Gilles Sousa Augusto; Xuelan Liu; Xinyue Chang. 2021. "BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced." , no. : 1.

Preprint content
Published: 04 March 2021
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Background Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein. Objective We aimed to assess how mutations in the SARS-CoV-2 RBD affect receptor affinity to angiotensin-converting enzyme 2 (ACE2) and neutralization by anti-RBD serum antibodies. Methods We produced a SARS-CoV-2 RBD mutant (RBDmut) with key mutations (E484K, K417N, N501Y) from the newly emerged Brazilian variant. Using Biolayer Interferometry, we analyzed the binding of this mutant to ACE2, and the susceptibility to neutralization by sera from vaccinated mice and COVID-19 convalescent patients. Results Kinetic profiles showed increased RBDmut - ACE2 affinity compared to RBDwt, and binding of vaccine-elicited or convalescent sera was significantly reduced. Likewise, both sera types showed significantly reduced ability to block RBDmut - ACE2 binding indicating that antibodies induced by RBDwt have reduced capability to neutralize mutant virus. Conclusion Our physiochemical data show enhanced infectivity and reduced neutralization by polyclonal antibodies of the Brazilian variant of SARS-CoV-2. Capsule summary SARS-CoV-2 variant with Brazilian RBD mutations shows increased ACE2 affinity and reduced susceptibility to blockage by vaccine-elicited and convalescent sera.

ACS Style

Monique Vogel; Xinyue Chang; Gilles Sousa Augusto; Mona O. Mohsen; Daniel E. Speiser; Martin F. Bachmann. SARS-CoV-2 variant with higher affinity to ACE2 shows reduced sera neutralization susceptibility. 2021, 1 .

AMA Style

Monique Vogel, Xinyue Chang, Gilles Sousa Augusto, Mona O. Mohsen, Daniel E. Speiser, Martin F. Bachmann. SARS-CoV-2 variant with higher affinity to ACE2 shows reduced sera neutralization susceptibility. . 2021; ():1.

Chicago/Turabian Style

Monique Vogel; Xinyue Chang; Gilles Sousa Augusto; Mona O. Mohsen; Daniel E. Speiser; Martin F. Bachmann. 2021. "SARS-CoV-2 variant with higher affinity to ACE2 shows reduced sera neutralization susceptibility." , no. : 1.

Comment
Published: 04 January 2021 in npj Vaccines
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Neutralizing antibody responses of SARS-CoV-2-infected patients may be low and of short duration. We propose here that coronaviruses employ a structural strategy to avoid strong and enduring antibody responses. Other viruses induce optimal and long-lived neutralizing antibody responses, thanks to 20 or more repetitive, rigid antigenic epitopes, spaced by 5–10 nm, present on the viral surface. Such arrays of repetitive and highly organized structures are recognized by the immune system as pathogen-associated structural patterns (PASPs), which are characteristic for pathogen surfaces. In contrast, coronaviruses are large particles with long spikes (S protein) embedded in a fluid membrane. Therefore, the neutralizing epitopes (which are on the S protein) are loosely “floating” and widely spaced by an average of about 25 nm. Consequently, recruitment of complement is poor and stimulation of B cells remains suboptimal, offering an explanation for the inefficient and short-lived neutralizing antibody responses.

ACS Style

Martin F. Bachmann; Mona O. Mohsen; Lisha Zha; Monique Vogel; Daniel E. Speiser. SARS-CoV-2 structural features may explain limited neutralizing-antibody responses. npj Vaccines 2021, 6, 1 -5.

AMA Style

Martin F. Bachmann, Mona O. Mohsen, Lisha Zha, Monique Vogel, Daniel E. Speiser. SARS-CoV-2 structural features may explain limited neutralizing-antibody responses. npj Vaccines. 2021; 6 (1):1-5.

Chicago/Turabian Style

Martin F. Bachmann; Mona O. Mohsen; Lisha Zha; Monique Vogel; Daniel E. Speiser. 2021. "SARS-CoV-2 structural features may explain limited neutralizing-antibody responses." npj Vaccines 6, no. 1: 1-5.

Journal article
Published: 13 November 2020 in Allergy
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Serological immunoassays that can identify protective immunity against SARS‐CoV‐2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed‐design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS‐CoV‐2 proteins and assessed the neutralizing activity of antibodies in patient sera. Consecutive patients admitted with confirmed SARS‐CoV‐2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in‐house enzyme‐linked immunosorbent assay utilizing recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein was developed and compared to three commercially available enzyme‐linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1) and a lateral flow immunoassay (LFI) based on full‐length spike protein. Neutralization assays with live SARS‐CoV‐2 were performed. One‐thousand four‐hundred and seventy‐seven individuals were included comprising 112 SARS‐CoV‐2 positives (defined as a positive real‐time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS‐CoV‐2 positive individuals, 96.3% showed full neutralization of live SARS‐CoV‐2 at serum dilutions ≥1:16, while none of the 6 SARS‐CoV‐2 negative sera revealed neutralizing activity. ELISAs targeting RBD and S1 protein of SARS‐CoV‐2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS‐CoV‐2.

ACS Style

Daniel Brigger; Michael P. Horn; Luke F. Pennington; Abigail E. Powell; Denise Siegrist; Benjamin Weber; Olivier Engler; Vanja Piezzi; Lauro Damonti; Patricia Iseli; Christoph Hauser; Tanja K. Froehlich; Peter M. Villiger; Martin F. Bachmann; Stephen L. Leib; Pascal Bittel; Martin Fiedler; Carlo R. Largiadèr; Jonas Marschall; Hanspeter Stalder; Peter S. Kim; Theodore S. Jardetzky; Alexander Eggel; Michael Nagler. Accuracy of serological testing for SARS‐CoV‐2 antibodies: First results of a large mixed‐method evaluation study. Allergy 2020, 76, 853 -865.

AMA Style

Daniel Brigger, Michael P. Horn, Luke F. Pennington, Abigail E. Powell, Denise Siegrist, Benjamin Weber, Olivier Engler, Vanja Piezzi, Lauro Damonti, Patricia Iseli, Christoph Hauser, Tanja K. Froehlich, Peter M. Villiger, Martin F. Bachmann, Stephen L. Leib, Pascal Bittel, Martin Fiedler, Carlo R. Largiadèr, Jonas Marschall, Hanspeter Stalder, Peter S. Kim, Theodore S. Jardetzky, Alexander Eggel, Michael Nagler. Accuracy of serological testing for SARS‐CoV‐2 antibodies: First results of a large mixed‐method evaluation study. Allergy. 2020; 76 (3):853-865.

Chicago/Turabian Style

Daniel Brigger; Michael P. Horn; Luke F. Pennington; Abigail E. Powell; Denise Siegrist; Benjamin Weber; Olivier Engler; Vanja Piezzi; Lauro Damonti; Patricia Iseli; Christoph Hauser; Tanja K. Froehlich; Peter M. Villiger; Martin F. Bachmann; Stephen L. Leib; Pascal Bittel; Martin Fiedler; Carlo R. Largiadèr; Jonas Marschall; Hanspeter Stalder; Peter S. Kim; Theodore S. Jardetzky; Alexander Eggel; Michael Nagler. 2020. "Accuracy of serological testing for SARS‐CoV‐2 antibodies: First results of a large mixed‐method evaluation study." Allergy 76, no. 3: 853-865.

Preprint content
Published: 29 September 2020
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Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B-cells and other innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T=3 icosahedron particles. They can be easily expressed in an E. coli host system and package ssRNA during the expression process. Recently, we have engineered CCMV-VLPs by incorporating the universal tetanus toxoid (TT) epitope at the N-terminus. The modified CCMVTT-VLPs successfully form icosahedral particles T=3, with a diameter of ~30nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMVTT-VLPs results in the formation of Rod-shaped VLPs, ~1μm in length and ~30nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMVTT-VLPs and Rod-shaped CCMVTT-VLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Round-shaped CCMVTT-VLPs are more efficient in draining to secondary lymphoid organs to charge antigen-presenting cells as well as B-cells. Furthermore, compared to Rod-shaped CCMVTT-VLPs, Round-shaped CCMVTT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMVTT-VLPs could also polarize the induced immune response towards TH1. Up to our knowledge, this is the first study investigating and comparing the draining kinetics and immunogenicity of one and the same VLP monomer forming nano-sized icosahedrons or rods in the micrometer size.

ACS Style

Simon Zinkhan; Anete Ogrina; Ina Balke; Gunta Reseviča; Andris Zeltins; Simone De Brot; Cyrill Lipp; Xinyue Chang; Lisha Zha; Monique Vogel; Martin Fabian Bachmann; Mona O Mohsen. The impact of size on particle drainage dynamics and antibody response. 2020, 1 .

AMA Style

Simon Zinkhan, Anete Ogrina, Ina Balke, Gunta Reseviča, Andris Zeltins, Simone De Brot, Cyrill Lipp, Xinyue Chang, Lisha Zha, Monique Vogel, Martin Fabian Bachmann, Mona O Mohsen. The impact of size on particle drainage dynamics and antibody response. . 2020; ():1.

Chicago/Turabian Style

Simon Zinkhan; Anete Ogrina; Ina Balke; Gunta Reseviča; Andris Zeltins; Simone De Brot; Cyrill Lipp; Xinyue Chang; Lisha Zha; Monique Vogel; Martin Fabian Bachmann; Mona O Mohsen. 2020. "The impact of size on particle drainage dynamics and antibody response." , no. : 1.

Editorial
Published: 10 August 2020 in Viruses
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Virus-like particles (VLPs) have become a key tool for vaccine developers and manufacturers

ACS Style

Monique Vogel; Martin F. Bachmann. Special Issue “Virus-Like Particle Vaccines”. Viruses 2020, 12, 872 .

AMA Style

Monique Vogel, Martin F. Bachmann. Special Issue “Virus-Like Particle Vaccines”. Viruses. 2020; 12 (8):872.

Chicago/Turabian Style

Monique Vogel; Martin F. Bachmann. 2020. "Special Issue “Virus-Like Particle Vaccines”." Viruses 12, no. 8: 872.

Review
Published: 22 July 2020 in Vaccines
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Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

ACS Style

Daniel E. Speiser; Martin F. Bachmann. COVID-19: Mechanisms of Vaccination and Immunity. Vaccines 2020, 8, 404 .

AMA Style

Daniel E. Speiser, Martin F. Bachmann. COVID-19: Mechanisms of Vaccination and Immunity. Vaccines. 2020; 8 (3):404.

Chicago/Turabian Style

Daniel E. Speiser; Martin F. Bachmann. 2020. "COVID-19: Mechanisms of Vaccination and Immunity." Vaccines 8, no. 3: 404.

Invited review
Published: 30 May 2020 in Immunological Reviews
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Vaccines need to be rationally designed in order be delivered to the immune system for maximizing induction of dynamic immune responses. Virus‐like particles (VLPs) are ideal platforms for such 3D vaccines, as they allow the display of complex and native antigens in a highly repetitive form on their surface and can easily reach lymphoid organs in intact form for optimal activation of B and T cells. Adjusting size and zeta potential may allow investigators to further fine‐tune delivery to lymphoid organs. An additional way to alter vaccine transfer to lymph nodes and spleen may be the formulation with micron‐sized adjuvants that creates a local depot and results in a slow release of antigen and adjuvant. Ideally, the adjuvant in addition stimulates the innate immune system. The dynamics of the immune response may be further enhanced by inclusion of Toll‐like receptor ligands, which many VLPs naturally package. Hence, considering the 3Ds in vaccine development may allow for enhancement of their attributes to tackle complex diseases, not usually amenable to conventional vaccine strategies.

ACS Style

Mona O. Mohsen; Gilles Augusto; Martin F. Bachmann. The 3Ds in virus‐like particle based‐vaccines: “ Design, Delivery and Dynamics ”. Immunological Reviews 2020, 296, 155 -168.

AMA Style

Mona O. Mohsen, Gilles Augusto, Martin F. Bachmann. The 3Ds in virus‐like particle based‐vaccines: “ Design, Delivery and Dynamics ”. Immunological Reviews. 2020; 296 (1):155-168.

Chicago/Turabian Style

Mona O. Mohsen; Gilles Augusto; Martin F. Bachmann. 2020. "The 3Ds in virus‐like particle based‐vaccines: “ Design, Delivery and Dynamics ”." Immunological Reviews 296, no. 1: 155-168.

Journal article
Published: 21 April 2020 in Allergy
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Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3 ) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre-existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is presensitized to the antigen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT redirect the Th2 immune response towards Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three-to-five-year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.

ACS Style

Erika Jensen‐Jarolim; Martin F. Bachmann; Sergio Bonini; Lars Jacobsen; Marek Jutel; Ludger Klimek; Vera Mahler; Ralph Mösges; Philippe Moingeon; Robyn E. O´hehir; Oscar Palomares; Oliver Pfaar; Harald Renz; Claudio Rhyner; Franziska Roth‐Walter; Michael Rudenko; Johannes Savolainen; Carsten B. Schmidt‐Weber; Claudia Traidl‐Hoffmann; Thomas Kündig. State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy 2020, 75, 746 -760.

AMA Style

Erika Jensen‐Jarolim, Martin F. Bachmann, Sergio Bonini, Lars Jacobsen, Marek Jutel, Ludger Klimek, Vera Mahler, Ralph Mösges, Philippe Moingeon, Robyn E. O´hehir, Oscar Palomares, Oliver Pfaar, Harald Renz, Claudio Rhyner, Franziska Roth‐Walter, Michael Rudenko, Johannes Savolainen, Carsten B. Schmidt‐Weber, Claudia Traidl‐Hoffmann, Thomas Kündig. State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy. 2020; 75 (4):746-760.

Chicago/Turabian Style

Erika Jensen‐Jarolim; Martin F. Bachmann; Sergio Bonini; Lars Jacobsen; Marek Jutel; Ludger Klimek; Vera Mahler; Ralph Mösges; Philippe Moingeon; Robyn E. O´hehir; Oscar Palomares; Oliver Pfaar; Harald Renz; Claudio Rhyner; Franziska Roth‐Walter; Michael Rudenko; Johannes Savolainen; Carsten B. Schmidt‐Weber; Claudia Traidl‐Hoffmann; Thomas Kündig. 2020. "State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI)." Allergy 75, no. 4: 746-760.

Journal article
Published: 01 April 2020 in Journal of Allergy and Clinical Immunology
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Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial, and economic burden for affected patients and wider society. A causal, safe, and effective therapy is not yet available. We sought to develop an immunogenic, protective, and nonreactogenic vaccine candidate against peanut allergy based on virus-like particles (VLPs) coupled to single peanut allergens. To generate vaccine candidates, extracts of roasted peanut (Ara R) or the single allergens Ara h 1 or Ara h 2 were coupled to immunologically optimized Cucumber Mosaic Virus-derived VLPs (CuMVtt). BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum. Immunotherapy consisted of a single subcutaneous injection of CuMVtt coupled to Ara R, Ara h 1, or Ara h 2. The vaccines CuMVtt-Ara R, CuMVtt-Ara h 1, and CuMVtt-Ara h 2 protected peanut-sensitized mice against anaphylaxis after intravenous challenge with the whole peanut extract. Vaccines did not cause allergic reactions in sensitized mice. CuMVtt-Ara h 1 was able to induce specific IgG antibodies, diminished local reactions after skin prick tests, and reduced the infiltration of the gastrointestinal tract by eosinophils and mast cells after oral challenge with peanut. The ability of CuMVtt-Ara h 1 to protect against challenge with the whole extract was mediated by IgG, as shown via passive IgG transfer. FcγRIIb was required for protection, indicating that immune complexes with single allergens were able to block the allergic response against the whole extract, consisting of a complex allergen mixture. Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel therapy against peanut allergy with a favorable safety profile.

ACS Style

Federico Storni; Andris Zeltins; Ina Balke; Matthew D. Heath; Matthias F. Kramer; Murray A. Skinner; Lisha Zha; Elisa Roesti; Paul Engeroff; Lukas Muri; Diego von Werdt; Thomas Gruber; Mark Cragg; Malgorzata Mlynarczyk; Thomas M. Kündig; Monique Vogel; Martin F. Bachmann. Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens. Journal of Allergy and Clinical Immunology 2020, 145, 1240 -1253.e3.

AMA Style

Federico Storni, Andris Zeltins, Ina Balke, Matthew D. Heath, Matthias F. Kramer, Murray A. Skinner, Lisha Zha, Elisa Roesti, Paul Engeroff, Lukas Muri, Diego von Werdt, Thomas Gruber, Mark Cragg, Malgorzata Mlynarczyk, Thomas M. Kündig, Monique Vogel, Martin F. Bachmann. Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens. Journal of Allergy and Clinical Immunology. 2020; 145 (4):1240-1253.e3.

Chicago/Turabian Style

Federico Storni; Andris Zeltins; Ina Balke; Matthew D. Heath; Matthias F. Kramer; Murray A. Skinner; Lisha Zha; Elisa Roesti; Paul Engeroff; Lukas Muri; Diego von Werdt; Thomas Gruber; Mark Cragg; Malgorzata Mlynarczyk; Thomas M. Kündig; Monique Vogel; Martin F. Bachmann. 2020. "Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens." Journal of Allergy and Clinical Immunology 145, no. 4: 1240-1253.e3.

Journal article
Published: 06 March 2020 in Viruses
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An innovative approach was tested to treat cat allergy in humans by vaccinating cats with Fel-CuMV (HypoCatTM), a vaccine against the major cat allergen Fel d 1 based on virus-like particles derived from cucumber mosaic virus (CuMV-VLPs). Upon vaccination, cats develop neutralizing antibodies against the allergen Fel d 1, which reduces the level of reactive allergen, thus lowering the symptoms or even preventing allergic reactions in humans. The combined methodological field study included ten cat-allergic participants who lived together with their cats (n = 13), that were immunized with Fel-CuMV. The aim was to determine methods for measuring a change in allergic symptoms. A home-based provocation test (petting time and organ specific symptom score (OSSS)) and a general weekly (or monthly) symptom score (G(W)SS) were used to assess changes in allergic symptoms. The petting time until a pre-defined level of allergic symptoms was reached increased already early after vaccination of the cats and was apparent over the course of the study. In addition, the OSSS after provocation and G(W)SS recorded a persistent reduction in symptoms over the study period and could serve for long-term assessment. Hence, the immunization of cats with HypoCatTM (Fel-CuMV) may have a positive impact on the cat allergy of the owner, and changes could be assessed by the provocation test as well as G(W)SS.

ACS Style

Franziska Thoms; Stefanie Haas; Aline Erhart; Claudia S. Nett; Silvia Rüfenacht; Nicole Graf; Arnis Strods; Gauravraj Patil; Thonur Leenadevi; Michael C. Fontaine; Lindsey A. Toon; Gary T. Jennings; Gabriela Senti; Thomas M. Kündig; Martin F. Bachmann. Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners. Viruses 2020, 12, 288 .

AMA Style

Franziska Thoms, Stefanie Haas, Aline Erhart, Claudia S. Nett, Silvia Rüfenacht, Nicole Graf, Arnis Strods, Gauravraj Patil, Thonur Leenadevi, Michael C. Fontaine, Lindsey A. Toon, Gary T. Jennings, Gabriela Senti, Thomas M. Kündig, Martin F. Bachmann. Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners. Viruses. 2020; 12 (3):288.

Chicago/Turabian Style

Franziska Thoms; Stefanie Haas; Aline Erhart; Claudia S. Nett; Silvia Rüfenacht; Nicole Graf; Arnis Strods; Gauravraj Patil; Thonur Leenadevi; Michael C. Fontaine; Lindsey A. Toon; Gary T. Jennings; Gabriela Senti; Thomas M. Kündig; Martin F. Bachmann. 2020. "Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners." Viruses 12, no. 3: 288.

Correction
Published: 20 February 2020 in Vaccines
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The authors wish to make the following correction to their paper

ACS Style

Gustavo Cabral-Miranda; Stephanie M. Lim; Mona O. Mohsen; Ilya V. Pobelov; Elisa S. Roesti; Matthew D. Heath; Murray A. Skinner; Matthias F. Kramer; Byron E. E. Martina; Martin F. Bachmann. Correction: Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection. Vaccines 2019, 7, 72. Vaccines 2020, 8, 94 .

AMA Style

Gustavo Cabral-Miranda, Stephanie M. Lim, Mona O. Mohsen, Ilya V. Pobelov, Elisa S. Roesti, Matthew D. Heath, Murray A. Skinner, Matthias F. Kramer, Byron E. E. Martina, Martin F. Bachmann. Correction: Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection. Vaccines 2019, 7, 72. Vaccines. 2020; 8 (1):94.

Chicago/Turabian Style

Gustavo Cabral-Miranda; Stephanie M. Lim; Mona O. Mohsen; Ilya V. Pobelov; Elisa S. Roesti; Matthew D. Heath; Murray A. Skinner; Matthias F. Kramer; Byron E. E. Martina; Martin F. Bachmann. 2020. "Correction: Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection. Vaccines 2019, 7, 72." Vaccines 8, no. 1: 94.

Original article
Published: 09 December 2019 in Allergy
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Background Insect bite hypersensitivity (IBH) is the most common seasonal pruritic allergic dermatitis of horses occurring upon insect bites. In recent years, a major role for IL‐31 in allergic pruritus of humans, monkeys, dogs and mice was acknowledged. Objective Here, we investigate the role of IL‐31 in IBH of horses and developed a therapeutic vaccine against equine IL‐31 (eIL‐31). Methods IL‐31 levels were quantified in allergen‐stimulated PBMCs and skin punch biopsies of IBH lesions and healthy skin from IBH‐affected and healthy horses. The vaccine consisted of eIL‐31 covalently coupled to a virus‐like particle (VLP) derived from cucumber mosaic virus containing a tetanus toxoid universal T‐cell epitope (CuMVTT). Eighteen IBH‐affected horses were recruited and immunized with 300 μg of eIL‐31‐CuMVTT vaccine or placebo and IBH severity score was recorded. Results IL‐31 was increased in PBMCs and exclusively detectable in skin lesions of IBH‐affected horses. Vaccination against eIL‐31 reduced delta clinical scores when compared to previous untreated IBH season of the same horses and to placebo treated horses in the same year. The vaccine was well tolerated without safety concerns throughout the study. Conclusion TH2‐derived IL‐31 is involved in IBH pathology and accordingly the immunotherapeutic vaccination approach targeting IL‐31 alleviated clinical scores in affected horses.

ACS Style

Florian Olomski; Victoria Fettelschoss; Sigridur Jonsdottir; Katharina Birkmann; Franziska Thoms; Eliane Marti; Martin F. Bachmann; Thomas M. Kündig; Antonia Fettelschoss‐Gabriel. Interleukin 31 in insect bite hypersensitivity—Alleviating clinical symptoms by active vaccination against itch. Allergy 2019, 75, 862 -871.

AMA Style

Florian Olomski, Victoria Fettelschoss, Sigridur Jonsdottir, Katharina Birkmann, Franziska Thoms, Eliane Marti, Martin F. Bachmann, Thomas M. Kündig, Antonia Fettelschoss‐Gabriel. Interleukin 31 in insect bite hypersensitivity—Alleviating clinical symptoms by active vaccination against itch. Allergy. 2019; 75 (4):862-871.

Chicago/Turabian Style

Florian Olomski; Victoria Fettelschoss; Sigridur Jonsdottir; Katharina Birkmann; Franziska Thoms; Eliane Marti; Martin F. Bachmann; Thomas M. Kündig; Antonia Fettelschoss‐Gabriel. 2019. "Interleukin 31 in insect bite hypersensitivity—Alleviating clinical symptoms by active vaccination against itch." Allergy 75, no. 4: 862-871.