Article
Immunology
Nicholas P. Wayham, Ariel R. Niedecken, Jan Fredrik Simons, Yao Y. Chiang, Angelica Medina-Cucurella, Rena A. Mizrahi, Ellen K. Wagner, Ashley Gras, Ilana Segal, Peyton Witte, Alexis Enstrom, Aristea Bountouvas, Sabrina M. Nelson, Tess Weinberger, David Tan, Michael A. Asensio, Alagu Subramanian, Yoong Wearn Lim, Adam S. Adler, Sheila M. Keating
Summary: Emergent SARS-CoV-2 variants can develop resistance to existing treatments. A recombinant polyclonal antibody enriched for antiancestral and anti-omicron BA.2 receptor binding domain activity may help prevent future drug resistance. This approach is significant for developing antibody therapeutics against current and future SARS-CoV-2 threats.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Joanna Luczkowiak, Pauline Radreau, Ludovic Nguyen, Nuria Labiod, Fatima Lasala, Francisco Veas, Cecile Helene Herbreteau, Rafael Delgado
Summary: Polyclonal equine anti-SARS-CoV-2 F(ab')2 antibodies demonstrate high neutralizing potency against all tested VoCs, including Omicron subvariants, which may be attributed to a repertoire of antibodies targeting conserved epitopes in different regions of the spike protein. Further clinical investigation of equine polyclonal F(ab')2 antibodies as a novel therapeutic strategy against COVID-19 is warranted.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Medicine, Research & Experimental
Courtney Voss, Sally Esmail, Xuguang Liu, Michael J. Knauer, Suzanne Ackloo, Tomonori Kaneko, Lori Lowes, Peter Stogios, Almagul Seitova, Ashley Hutchinson, Farhad Yusifov, Tatiana Skarina, Elena Evdokimova, Peter Loppnau, Pegah Ghiabi, Taraneh Haijan, Shanshan Zhong, Husam Abdoh, Benjamin D. Hedley, Vipin Bhayana, Claudio M. Martin, Marat Slessarev, Benjamin Chin-Yee, Douglas D. Fraser, Ian Chin-Yee, Shawn S. C. Li
Summary: This study identified linear epitopes from SARS-CoV-2 proteins and demonstrated their ability to provide higher resolution antibody profiling compared to traditional antigens. The antibody responses to specific epitopes were found to be correlated with clinical severity and patient survival. Additionally, mutations in the coronavirus variant B.1.1.7 were shown to alter the specificity of corresponding epitopes.
Article
Multidisciplinary Sciences
Theron Gilliland, Matthew Dunn, Yanan Liu, Maria D. H. Alcorn, Yutaka Terada, Shauna Vasilatos, Jeneveve Lundy, Rong Li, Sham Nambulli, Deanna Larson, Paul Duprex, Hua Wu, Thomas Luke, Christoph Bausch, Kristi Egland, Eddie Sullivan, Zhongde Wang, William B. Klimstra
Summary: The rapid evolution of the SARS-CoV-2 virus has led to the emergence of variants with spike protein mutations that may evade antibody neutralization, transmit more efficiently, or exhibit altered virulence. A human polyclonal antibody called SAB-185 was found to have strong neutralizing effects against multiple variants in vitro and provided protection in animal experiments against lethal and non-lethal strains. This suggests that SAB-185 may be an effective immunotherapy even in the presence of ongoing viral mutation.
Article
Medicine, General & Internal
Qiaoli Peng, Runhong Zhou, Yuewen Wang, Meiqing Zhao, Na Liu, Shuang Li, Haode Huang, Dawei Yang, Ka-Kit Au, Hui Wang, Kwan Man, Kwok-Yung Yuen, Zhiwei Chen
Summary: This study compares the immunogenicity and durability of BNT162b2-mRNA and CoronaVac-inactivated vaccines in fully vaccinated individuals in Hong Kong. The results show that both vaccines induce neutralizing antibodies and spike-specific CD4 T cell responses, but CoronaVac vaccine induces lower immune responses compared to BNT162b2 vaccine. Against SARS-CoV-2 variants of concern, CoronaVac vaccine shows weaker neutralizing antibody responses compared to BNT162b2 vaccine. Three months after vaccination, neutralizing antibody levels to variants of concern decrease, along with waning memory T cell responses, especially among CoronaVac vaccine recipients.
Article
Multidisciplinary Sciences
Rohitash Chandra, Chaarvi Bansal, Mingyue Kang, Tom Blau, Vinti Agarwal, Pranjal Singh, Laurence O. W. Wilson, Seshadri Vasan
Summary: Due to the high mutation rate, COVID-19 variants like Delta and Omicron emerged with altered viral properties, causing severe transmission and death rates. These variants had a major impact on global medical systems, travel, productivity, and the world economy. This paper introduces a framework that utilizes unsupervised machine learning methods to discriminate and visualize the associations between major COVID-19 variants based on their genome sequences. The framework combines dimensionality reduction and clustering techniques to process RNA sequences, with the potential to effectively distinguish between major variants and identify emerging variants in the future.
Review
Virology
Abdul Aziz Al-Fattah Yahaya, Kanwal Khalid, Hui Xuan Lim, Chit Laa Poh
Summary: SARS-CoV-2 has caused a global pandemic, resulting in over 673 million infections and 6.85 million deaths. The current mRNA and viral-vectored vaccines have shown good efficacy against the SARS-CoV-2 Wuhan strain, but are less effective against highly transmissible variants like Omicron. Development of next-generation vaccines is urgently needed to provide broad protection.
Article
Agriculture, Dairy & Animal Science
Jesse W. Wotring, Reid Fursmidt, Loren Ward, Jonathan Z. Sexton
Summary: Bovine lactoferrin (bLF), a naturally occurring glycoprotein found in milk, has been found to strongly inhibit SARS-CoV-2 infection through direct entry inhibition and immunomodulatory mechanisms. This study shows that bLF is effective against different strains of the virus, including the B.1.1.7 variant. The study also highlights the potential of lactoferrin as a clinical candidate for the treatment or prevention of SARS-CoV-2.
JOURNAL OF DAIRY SCIENCE
(2022)
Article
Microbiology
Katharina S. Schmitz, Daryl Geers, Rory D. de Vries, T. Francesca Bovier, Anna Z. Mykytyn, Corine H. Geurts van Kessel, Bart L. Haagmans, Matteo Porotto, Rik L. de Swart, Anne Moscona
Summary: SARS-CoV-2 continues to spread globally, with new variants that evade immunity generated by vaccines and previous strains. Fusion-inhibitory peptides may provide an intervention strategy that is not affected by viral evolution.
Article
Cell Biology
Lisa H. Tostanoski, Jingyou Yu, Noe B. Mercado, Katherine McMahan, Catherine Jacob-Dolan, Amanda J. Martinot, Cesar Piedra-Mora, Tochi Anioke, Aiquan Chang, Victoria M. Giffin, David L. Hope, Huahua Wan, Esther A. Bondzie, Shant H. Mahrokhian, Linda M. Wrijil, Katherine Bauer, Laurent Pessaint, Maciel Porto, Joseph Piegols, Andrew Faudree, Brittany Spence, Swagata Kar, Fatima Amanat, Florian Krammer, Hanne Andersen, Mark G. Lewis, Frank Wegmann, Roland Zahn, Hanneke Schuitemaker, Dan H. Barouch
Summary: This study explored how mutations in spike proteins of different SARS-CoV-2 variants affect natural and vaccine-induced immunity, finding that primary infection with the WA1/2020 strain provided strong protection, while antibodies induced by the Ad26.COV2.S vaccine showed reduced neutralizing activity against the B.1.351 strain but still offered effective protection.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, General & Internal
Peter J. Halfmann, Steven J. Frey, Kathryn Loef, Makoto Kuroda, Tadashi Maemura, Tammy Armbrust, Jie E. Yang, Yixuan J. Hou, Ralph Baric, Elizabeth R. Wright, Yoshihiro Kawaoka, Ravi S. Kane
Summary: Researchers have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen. The vaccine showed efficacy against SARS-CoV-2 variants and other coronaviruses.
Article
Cell Biology
Monika Kumari, Shih-Chieh Su, Kang-Hao Liang, Hsiu-Ting Lin, Yu-Feng Lu, Kai-Chi Chen, Wan-Yu Chen, Han-Chung Wu
Summary: In this study, full-length spike mRNAs were designed for different variants of SARS-CoV-2 and incorporated into monovalent or bivalent mRNA-lipid nanoparticle vaccines. The results showed that monovalent vaccines were only effective against the same type of virus, while bivalent vaccines could neutralize multiple variant strains, especially the BA.5 + WT combination which demonstrated high neutralization against various VOCs. Combining two mRNA sequences may be an effective strategy to develop a broadly protective SARS-CoV-2 vaccine against variant strains.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Medicine, General & Internal
Vanesa Seery, Silvina Raiden, Constanza Russo, Mauricio Borda, Largion Herrera, Macarena Uranga, Augusto Varese, Maria Marco del Pont, Carina Chirino, Constanza Erramuspe, Laura Silvana Alvarez, Melisa Lenoir, Laura Daniela Morales, Carolina Davenport, Alexsa Alarcon Flores, Soledad Huespe Auchter, Yanina Ruiz, Liliana Monsalvo, Laura Sastoque, Magali Gavazzi, Ignacio Mazzitelli, Facundo Di Diego, Yesica Longueira, Bianca Mazzitelli, Ines Sananez, Norberto De Carli, Mirna Marcela Biglione, Juan Martin Gomez Penedo, Ana Ceballos, Natalia Laufer, Fernando Ferrero, Jorge Geffner, Lourdes Arruvito
Summary: This observational study compared the antibody response between unvaccinated infected children and adults. The study found that unvaccinated infected children mount a more potent and sustained antibody response compared to adults, which is further increased after vaccination. Further studies are needed to optimize vaccination strategies for children.
Article
Immunology
Aleha Pillay, Avani Yeola, Fiona Tea, Martina Denkova, Samuel Houston, Rebecca Burrell, Vera Merheb, Fiona X. Z. Lee, Joseph A. Lopez, Lilly Moran, Ajay Jadhav, Katrina Sterling, Catherine L. Lai, Tennille L. Vitagliano, Anupriya Aggarwal, Dan Catchpoole, Nicholas Wood, Tri Giang Phan, Ralph Nanan, Peter Hsu, Stuart G. Turville, Philip N. Britton, Fabienne Brilot
Summary: It is important to compare the breadth of viral and vaccine cross-reactivity towards the ever-mutating spike protein among children and adults. Our study found that there was no significant difference in the antibody response to variants of concern between children and adults. Vaccinated individuals showed similar immunoreactivity profiles across variants compared to naturally infected individuals.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Review
Immunology
Aline Miranda Scovino, Elizabeth Chen Dahab, Gustavo Fioravanti Vieira, Leonardo Freire-de-Lima, Celio Geraldo Freire-de-Lima, Alexandre Morrot
Summary: The variants of the SARS-CoV-2 virus, including Alpha, Beta, Gamma, Delta, and Omicron, have mutations in the spike protein that can affect the virus's characteristics, such as its ability to bind to host cells, transmissibility, and immune evasion. Ongoing genetic monitoring of the pandemic coronavirus is crucial to identify potential new variants that can bypass host defenses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Soumya Mukherjee, Andris Jankevics, Florian Busch, Markus Lubeck, Yang Zou, Gary Kruppa, Albert J. R. Heck, Richard A. Scheltema, Karli R. Reiding
Summary: Ion mobility enables spatial separation of ions in the gas phase, providing information about their size. The timsTOF Pro device can physically separate N-glycopeptides from nonmodified peptides and produce high-quality fragmentation spectra. This method allows for the effective selection of analytes of interest based on the clear cluster in the mobiologram formed by the glycan moieties enlarging the size of glycopeptides.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Chemistry, Multidisciplinary
Evolene Desligniere, Amber Rolland, Eduard H. T. M. Ebberink, Victor Yin, Albert J. R. Heck
Summary: Native mass spectrometry is widely used for determining the mass of intact proteins and their biomolecular assemblies. However, it can be challenging for heterogeneous protein complexes. In 2012, an Orbitrap-based mass analyzer with extended mass range was introduced, enabling high-resolution mass spectra of large protein assemblies and single ion measurements. This led to the development of single-molecule Orbitrap-based charge detection mass spectrometry in 2020, which has opened doors for innovative research in various systems.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Gunasekaran Subramaniam, Katharina Schleicher, Duangnapa Kovanich, Anna Zerio, Milda Folkmanaite, Ying-Chi Chao, Nicoletta C. Surdo, Andreas Koschinski, Jianshu Hu, Arjen Scholten, Albert J. R. Heck, Maria Ercu, Anastasiia Sholokh, Kyung Chan Park, Enno Klussmann, Viviana Meraviglia, Milena Bellin, Sara Zanivan, Svenja Hester, Shabaz Mohammed, Manuela Zaccolo
Summary: In this study, previously unrecognized cAMP nanodomains associated with beta-adrenergic stimulation were identified using an integrated phosphoproteomics approach and network analysis. The composition and function of one of these nanodomains were validated. The findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors.
CIRCULATION RESEARCH
(2023)
Article
Biochemical Research Methods
Shelley Jager, Dario A. T. Cramer, Albert J. R. Heck
Summary: Alpha-1-antitrypsin (A1AT) has been suggested as a potential biomarker for distinguishing healthy and diseased individuals. However, the variability of the SERPINA1 gene in the general population may affect A1AT expression and serum protein levels, which are often overlooked in proteomics studies. This study found significant differences in allele-specific protein serum levels of A1AT among heterozygous donors, suggesting the importance of considering these factors when analyzing A1AT as a potential serum biomarker.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Anjusha Mathew, Frans Giskes, Alexandros Lekkas, Jean-Francois Greisch, Gert B. Eijkel, Ian G. M. Anthony, Kyle Fort, Albert J. R. Heck, Dimitris Papanastasiou, Alexander A. Makarov, Shane R. Ellis, Ron M. A. Heeren
Summary: We discuss the design, development, and evaluation of an Orbitrap/time-of-flight (TOF) mass spectrometry-based instrument with integrated UV photodissociation (UVPD) and time/mass-to-charge ratio (m/z)-resolved imaging for studying the higher-order molecular structure of macromolecular assemblies (MMAs). The instrument combines a bespoke TOF analyzer with an ultrahigh mass range hybrid quadrupole-Orbitrap MS. It employs a 193nm excimer laser for photofragmenting MMA ions and uses microchannel plates (MCPs)-Timepix (TPX) quad and MCPs-phosphorscreen-TPX3CAM assemblies as axial and orthogonal imaging detectors. The instrument can operate in four different modes to measure UVPD-generated fragment ions with high-mass resolution or image them in a mass-resolved manner to reveal the relative positions of the UVPD fragments post-dissociation. This information is crucial for understanding the molecular structure and dissociation dynamics of MMAs in the gas phase.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Andrology
Min Zhang, Riccardo Zenezini Chiozzi, Elizabeth G. Bromfield, Albert J. R. Heck, J. Bernd Helms, Bart M. Gadella
Summary: This study aimed to identify the interacting partners of CRISP2. The interactions of these binding partners were investigated under different conditions. The results suggest that CRISP2 may act as a scaffold for protein complex formation and dissociation to ensure the correct positioning of proteins required for the acrosome reaction and zona pellucida penetration.
Article
Biology
Leire Aguinagalde Salazar, Maurits A. den Boer, Suzanne M. Castenmiller, Seline A. Zwarthoff, Carla de Haas, Piet C. Aerts, Frank J. Beurskens, Janine Schuurman, Albert J. R. Heck, Kok van Kessel, Suzan H. M. Rooijakkers
Summary: In this study, it is found that by modifying the structure of monoclonal antibodies (mAbs), the immune protection and bactericidal effect against Streptococcus pneumoniae can be improved. The modified mAbs effectively activate the complement system and recruit complement component C1 for bacterial clearance, enhancing the antibacterial activity against various serotypes of pneumococci. This study provides an important proof of concept for the future development of antibody therapies against encapsulated bacteria.
Article
Biotechnology & Applied Microbiology
Yen-Hsi Chen, Weihua Tian, Makiko Yasuda, Zilu Ye, Ming Song, Ulla Mandel, Claus Kristensen, Lorenzo Povolo, Andre R. A. Marques, Tomislav Caval, Albert J. R. Heck, Julio Lopes Sampaio, Ludger Johannes, Takahiro Tsukimura, Robert Desnick, Sergey Y. Y. Vakhrushev, Zhang Yang, Henrik Clausen
Summary: Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due to short circulation times and suboptimal biodistribution of the therapeutic enzymes. Researchers have engineered Chinese hamster ovary (CHO) cells to produce glycoengineered enzymes, which have improved circulation time and biodistribution. This glycoengineering approach, known as Long-Acting-GlycoDesign (LAGD), may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Beiping Miao, Zhaoqing Hu, Riccardo Mezzadra, Lotte Hoeijmakers, Astrid Fauster, Shangce Du, Zhi Yang, Melanie Sator-Schmitt, Helena Engel, Xueshen Li, Caroline Broderick, Guangzhi Jin, Raquel Gomez-Eerland, Lisette Rozeman, Xin Lei, Hitoshi Matsuo, Chen Yang, Ingrid Hofland, Dennis Peters, Annegien Broeks, Elke Laport, Annika Fitz, Xiyue Zhao, Mohamed A. A. Mahmoud, Xiujian Ma, Sandrine Sander, Hai-kun Liu, Guoliang Cui, Yu Gan, Wei Wu, Yanling Xiao, Albert J. R. Heck, Wenxian Guan, Scott W. Lowe, Hugo M. Horlings, Cun Wang, Thijn R. Brummelkamp, Christian U. Blank, Ton N. M. Schumacher, Chong Sun
Summary: The dysregulation of immune checkpoint molecules allows cancer cells to escape immune destruction. CD58, an important costimulatory ligand, is found to be positively regulated by CMTM6, which also interacts with PD-L1. The presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and the response to PD-L1-PD-1 blockade.
Article
Cell Biology
Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinie, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J. R. Heck, Judy Hirst, Nils-Goran Larsson
Summary: The mammalian respiratory chain complexes CI, CIII2, and CIV form a stable assembly called the respirasome, which is critical for cellular bioenergetics. By studying knockin mice with decreased levels of respirasomes, researchers found that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice. However, the alternate functions of respirasomes, such as regulating protein stability and preventing age-associated protein aggregation, need further investigation.
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Inge Gazi, Karli R. Reiding, Andre Groeneveld, Jan Bastiaans, Thom Huppertz, Albert J. R. Heck
Summary: We monitored the changes in bovine milk IgG over a 28-day period after calving, finding that IgG accounts for over 50% of protein content in colostrum but less than 3% in mature milk. The N-glycosylation profile of bovine milk IgG was found to be highly heterogeneous with over 40 glycoforms, and this profile changed significantly during lactation. We also identified the presence of IgG3 subtype in bovine milk, alongside IgG1 and IgG2. These findings are important for understanding calf's immune development and the nutritional value of bovine milk.
Article
Immunology
Kelly A. Dingess, Max Hoek, Danique M. H. van Rijswijk, Sem Tamara, Maurits A. den Boer, Tim Veth, Mirjam J. A. Damen, Arjan Barendregt, Michelle Romijn, Hannah G. Juncker, Britt J. van Keulen, Gestur Vidarsson, Johannes B. van Goudoever, Albert Bondt, Albert J. R. Heck
Summary: The most abundant immunoglobulin in the human body is IgA and it is found in high concentrations in mucosal lining and biofluids like milk. The structure and clonal repertoire of IgA1-containing molecular assemblies were analyzed using mass spectrometry-based approach in serum and milk from three donors. The results showed that serum IgA1 consists of two distinct structural populations, monomeric IgA1 and dimeric J-chain coupled IgA1, while IgA1 in milk is present only as secretory IgA (SIgA) with various assemblies. The IgA1-Fab repertoires in serum and milk were also found to be different.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)