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More than one-third of the world's population is exposed to Plasmodium vivax malaria, mainly in Asia1. P. vivax preferentially invades reticulocytes (immature red blood cells)2-4. Previous work has identified 11 parasite proteins involved in reticulocyte invasion, including erythrocyte binding protein 2 (ref. 5) and the reticulocyte-binding proteins (PvRBPs)6-10. PvRBP2b binds to the transferrin receptor CD71 (ref. 11), which is selectively expressed on immature reticulocytes12. Here, we identified CD98 heavy chain (CD98), a heteromeric amino acid transporter from the SLC3 family (also known as SLCA2), as a reticulocyte-specific receptor for the PvRBP2a parasite ligand using mass spectrometry, flow cytometry, biochemical and parasite invasion assays. We characterized the expression level of CD98 at the surface of immature reticulocytes (CD71+) and identified an interaction between CD98 and PvRBP2a expressed at the merozoite surface. Our results identify CD98 as an additional host membrane protein, besides CD71, that is directly associated with P. vivax reticulocyte tropism. These findings highlight the potential of using PvRBP2a as a vaccine target against P. vivax malaria.
Benoît Malleret; Abbas El Sahili; Matthew Zirui Tay; Guillaume Carissimo; Alice Soh Meoy Ong; Wisna Novera; Jianqing Lin; Rossarin Suwanarusk; Varakorn Kosaisavee; Trang T T Chu; Ameya Sinha; Shanshan Wu Howland; Yiping Fan; Jakub Gruszczyk; Wai-Hong Tham; Yves Colin; Sebastian Maurer-Stroh; Georges Snounou; Lisa F P Ng; Jerry Kok Yen Chan; Ann-Marie Chacko; Julien Lescar; Rajesh Chandramohanadas; François Nosten; Bruce Russell; Laurent Rénia. Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells. Nature Microbiology 2021, 6, 991 -999.
AMA StyleBenoît Malleret, Abbas El Sahili, Matthew Zirui Tay, Guillaume Carissimo, Alice Soh Meoy Ong, Wisna Novera, Jianqing Lin, Rossarin Suwanarusk, Varakorn Kosaisavee, Trang T T Chu, Ameya Sinha, Shanshan Wu Howland, Yiping Fan, Jakub Gruszczyk, Wai-Hong Tham, Yves Colin, Sebastian Maurer-Stroh, Georges Snounou, Lisa F P Ng, Jerry Kok Yen Chan, Ann-Marie Chacko, Julien Lescar, Rajesh Chandramohanadas, François Nosten, Bruce Russell, Laurent Rénia. Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells. Nature Microbiology. 2021; 6 (8):991-999.
Chicago/Turabian StyleBenoît Malleret; Abbas El Sahili; Matthew Zirui Tay; Guillaume Carissimo; Alice Soh Meoy Ong; Wisna Novera; Jianqing Lin; Rossarin Suwanarusk; Varakorn Kosaisavee; Trang T T Chu; Ameya Sinha; Shanshan Wu Howland; Yiping Fan; Jakub Gruszczyk; Wai-Hong Tham; Yves Colin; Sebastian Maurer-Stroh; Georges Snounou; Lisa F P Ng; Jerry Kok Yen Chan; Ann-Marie Chacko; Julien Lescar; Rajesh Chandramohanadas; François Nosten; Bruce Russell; Laurent Rénia. 2021. "Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells." Nature Microbiology 6, no. 8: 991-999.
Circulating red blood cells consist of young erythrocytes (early and late reticulocytes) and mature erythrocytes (normocytes). The human malaria parasites, Plasmodium falciparum and P. vivax, have a preference to invade reticulocytes during blood-stage infection. Rodent malaria parasites that also prefer reticulocytes could be useful tools to study human malaria reticulocyte invasion. However, previous tropism studies of rodent malaria are inconsistent from one another, making it difficult to compare cell preference of different parasite species and strains. In vivo measurements of cell tropism are also subjected to many confounding factors. Here we developed an ex vivo tropism assay for rodent malaria with highly purified fractions of murine reticulocytes and normocytes. We measured invasion into the different erythrocyte populations using flow cytometry and evaluated the tropism index of the parasite strains. We found that P. berghei ANKA displayed the strongest reticulocyte preference, followed by P. yoelii 17X1.1, whereas P. chabaudi AS and P. vinckei S67 showed mixed tropism. These preferences are intrinsic and were maintained at different reticulocyte and normocyte availabilities. Our study shed light on the true erythrocyte preference of the parasites and paves the way for future investigations on the receptor-ligand interactions mediating erythrocyte tropism.
Yew Wai Leong; Erica Qian Hui Lee; Laurent Rénia; Benoit Malleret. Rodent Malaria Erythrocyte Preference Assessment by an Ex Vivo Tropism Assay. Frontiers in Cellular and Infection Microbiology 2021, 11, 1 .
AMA StyleYew Wai Leong, Erica Qian Hui Lee, Laurent Rénia, Benoit Malleret. Rodent Malaria Erythrocyte Preference Assessment by an Ex Vivo Tropism Assay. Frontiers in Cellular and Infection Microbiology. 2021; 11 ():1.
Chicago/Turabian StyleYew Wai Leong; Erica Qian Hui Lee; Laurent Rénia; Benoit Malleret. 2021. "Rodent Malaria Erythrocyte Preference Assessment by an Ex Vivo Tropism Assay." Frontiers in Cellular and Infection Microbiology 11, no. : 1.
A significant proportion of COVID-19 patients will progress to critical illness requiring invasive mechanical ventilation. This accentuates the need for a therapy that can reduce the severity of COVID-19. Clinical trials have shown the effectiveness of remdesivir in shortening recovery time and decreasing progression to respiratory failure and mechanical ventilation. However, some studies have highlighted its lack of efficacy in patients on high-flow oxygen and mechanical ventilation. This study uncovers some underlying immune response differences between responders and non-responders to remdesivir treatment. Immunological analyses revealed an upregulation of tissue repair factors BDNF, PDGF-BB and PIGF-1, as well as an increase in ratio of Th2-associated cytokine IL-4 to Th1-associated cytokine IFN-γ. Serological profiling of IgG subclasses corroborated this observation, with significantly higher magnitude of increase in Th2-associated IgG2 and IgG4 responses. These findings help to identify the mechanisms of immune regulation accompanying successful remdesivir treatment in severe COVID-19 patients.
Yi-Hao Chan; Barnaby E. Young; Siew-Wai Fong; Ying Ding; Yun Shan Goh; Rhonda Sin-Ling Chee; Seow-Yen Tan; Shirin Kalimuddin; Paul A. Tambyah; Yee-Sin Leo; Lisa F. P. Ng; David Chien Lye; Laurent Renia. Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir. Frontiers in Immunology 2021, 12, 1 .
AMA StyleYi-Hao Chan, Barnaby E. Young, Siew-Wai Fong, Ying Ding, Yun Shan Goh, Rhonda Sin-Ling Chee, Seow-Yen Tan, Shirin Kalimuddin, Paul A. Tambyah, Yee-Sin Leo, Lisa F. P. Ng, David Chien Lye, Laurent Renia. Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir. Frontiers in Immunology. 2021; 12 ():1.
Chicago/Turabian StyleYi-Hao Chan; Barnaby E. Young; Siew-Wai Fong; Ying Ding; Yun Shan Goh; Rhonda Sin-Ling Chee; Seow-Yen Tan; Shirin Kalimuddin; Paul A. Tambyah; Yee-Sin Leo; Lisa F. P. Ng; David Chien Lye; Laurent Renia. 2021. "Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir." Frontiers in Immunology 12, no. : 1.
One of the key public health strategies in coronavirus 2019 disease (COVID-19) management is the early detection of infected individuals to limit the transmission. As a result, serological assays have been developed to complement PCR-based assays. Here, we report the development of a flow cytometry-based assay to detect antibodies against full-length SARS-CoV-2 Spike protein (S protein) in COVID-19 patients. The assay is time-efficient and sensitive, being able to capture the wider repertoire of antibodies against the S protein.
Yun Shan Goh; Lisa F.P. Ng; Laurent Renia. A flow cytometry-based assay for serological detection of anti-spike antibodies in COVID-19 patients. STAR Protocols 2021, 2, 100671 .
AMA StyleYun Shan Goh, Lisa F.P. Ng, Laurent Renia. A flow cytometry-based assay for serological detection of anti-spike antibodies in COVID-19 patients. STAR Protocols. 2021; 2 (3):100671.
Chicago/Turabian StyleYun Shan Goh; Lisa F.P. Ng; Laurent Renia. 2021. "A flow cytometry-based assay for serological detection of anti-spike antibodies in COVID-19 patients." STAR Protocols 2, no. 3: 100671.
In 2016, we reported the presence of Plasmodium vivax in Botswana through active case detection. A real-time PCR was used during a similar study in 10 districts to assess changes in the P. vivax prevalence. We assessed 1,614 children (2–13 years of age) for hemoglobin (Hb; g/dL) and Plasmodium parasites. The median age of all participants was 5.0 years (25th percentile, 3 years; 75th percentile, 8 years). The median Hb (g/dL) level was 12.1, but 18.3% of the participants had anemia (Hb < 11.0 g/dL); these participants were clustered in the younger than 5 years age group in all districts (P < 0.001). The risk of anemia decreased with age 5 years or older (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.197–0.34; P < 0.001). The prevalence rates of Plasmodium parasites were as follows: P. vivax, 12.7%; P. falciparum, 12.7%; P. malariae, 0.74%; and P. ovale (P. ovale curtisi), 0.68%. Mixed infection rates were as follows: P. falciparum and P. vivax, 2.35%; P. falciparum and P. ovale curtisi, 0.56%; P. vivax and P. malariae, 0.06%; and P. falciparum and P. malariae, 0.68%. The infections were largely asymptomatic (99.6%). Using logistic regression, the risk of infection with P. vivax was highest in Kweneng East (OR, 6.2; 95% CI, 2.9–13.1), followed by South East (OR, 5.6; 95% CI, 2.5–12.3) and Ngami (OR, 5.1; 95% CI, 2.2–12.0). Compared to the risk of infection for children younger than 5 years, the risk of infection decreased for children 5 years or older in regions with high rates of P. vivax and P. falciparum infections. P. vivax and P. falciparum have expanded within the asymptomatic population in Botswana; therefore, careful attention is required for their elimination.
Thato Motshoge; Daniel H. Haiyambo; Ruth Ayanful-Torgby; Larysa Aleksenko; Davies Ntebela; Benoit Malleret; Laurent Rénia; Elias Peloewetse; Giacomo Maria Paganotti; Isaac K. Quaye. Recent Molecular Assessment of Plasmodium vivax and Plasmodium falciparum Asymptomatic Infections in Botswana. The American Journal of Tropical Medicine and Hygiene 2021, 104, 2159 -2164.
AMA StyleThato Motshoge, Daniel H. Haiyambo, Ruth Ayanful-Torgby, Larysa Aleksenko, Davies Ntebela, Benoit Malleret, Laurent Rénia, Elias Peloewetse, Giacomo Maria Paganotti, Isaac K. Quaye. Recent Molecular Assessment of Plasmodium vivax and Plasmodium falciparum Asymptomatic Infections in Botswana. The American Journal of Tropical Medicine and Hygiene. 2021; 104 (6):2159-2164.
Chicago/Turabian StyleThato Motshoge; Daniel H. Haiyambo; Ruth Ayanful-Torgby; Larysa Aleksenko; Davies Ntebela; Benoit Malleret; Laurent Rénia; Elias Peloewetse; Giacomo Maria Paganotti; Isaac K. Quaye. 2021. "Recent Molecular Assessment of Plasmodium vivax and Plasmodium falciparum Asymptomatic Infections in Botswana." The American Journal of Tropical Medicine and Hygiene 104, no. 6: 2159-2164.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.
Daniel Asarnow; Bei Wang; Wen-Hsin Lee; Yuanyu Hu; Ching-Wen Huang; Bryan Faust; Patricia Miang Lon Ng; Eve Zi Xian Ngoh; Markus Bohn; David Bulkley; Andrés Pizzorno; Beatrice Ary; Hwee Ching Tan; Chia Yin Lee; Rabiatul Adawiyah Minhat; Olivier Terrier; Mun Kuen Soh; Frannie Jiuyi Teo; Yvonne Yee Chin Yeap; Shirley Gek Kheng Seah; Conrad En Zuo Chan; Emily Connelly; Nicholas J. Young; Sebastian Maurer-Stroh; Laurent Renia; Brendon John Hanson; Manuel Rosa-Calatrava; Aashish Manglik; Yifan Cheng; Charles S. Craik; Cheng-I Wang. Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Cell 2021, 184, 3192 -3204.e16.
AMA StyleDaniel Asarnow, Bei Wang, Wen-Hsin Lee, Yuanyu Hu, Ching-Wen Huang, Bryan Faust, Patricia Miang Lon Ng, Eve Zi Xian Ngoh, Markus Bohn, David Bulkley, Andrés Pizzorno, Beatrice Ary, Hwee Ching Tan, Chia Yin Lee, Rabiatul Adawiyah Minhat, Olivier Terrier, Mun Kuen Soh, Frannie Jiuyi Teo, Yvonne Yee Chin Yeap, Shirley Gek Kheng Seah, Conrad En Zuo Chan, Emily Connelly, Nicholas J. Young, Sebastian Maurer-Stroh, Laurent Renia, Brendon John Hanson, Manuel Rosa-Calatrava, Aashish Manglik, Yifan Cheng, Charles S. Craik, Cheng-I Wang. Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Cell. 2021; 184 (12):3192-3204.e16.
Chicago/Turabian StyleDaniel Asarnow; Bei Wang; Wen-Hsin Lee; Yuanyu Hu; Ching-Wen Huang; Bryan Faust; Patricia Miang Lon Ng; Eve Zi Xian Ngoh; Markus Bohn; David Bulkley; Andrés Pizzorno; Beatrice Ary; Hwee Ching Tan; Chia Yin Lee; Rabiatul Adawiyah Minhat; Olivier Terrier; Mun Kuen Soh; Frannie Jiuyi Teo; Yvonne Yee Chin Yeap; Shirley Gek Kheng Seah; Conrad En Zuo Chan; Emily Connelly; Nicholas J. Young; Sebastian Maurer-Stroh; Laurent Renia; Brendon John Hanson; Manuel Rosa-Calatrava; Aashish Manglik; Yifan Cheng; Charles S. Craik; Cheng-I Wang. 2021. "Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia." Cell 184, no. 12: 3192-3204.e16.
The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS‐CoV‐2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies and cellular immune phenotypes of asymptomatic patients with acute SARS‐CoV‐2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro‐inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro‐inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus‐specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS‐CoV‐2 was observed in asymptomatic patients. In addition, asymptomatic COVID‐19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro‐inflammatory and more protective immune responses against SARS‐CoV‐2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID‐19.
Yi‐Hao Chan; Siew‐Wai Fong; Chek‐Meng Poh; Guillaume Carissimo; Nicholas Kim‐Wah Yeo; Siti Naqiah Amrun; Yun Shan Goh; Jackwee Lim; Weili Xu; Rhonda Sin‐Ling Chee; Anthony Torres‐Ruesta; Cheryl Yi‐Pin Lee; Matthew Zirui Tay; Zi Wei Chang; Wen‐Hsin Lee; Bei Wang; Seow‐Yen Tan; Shirin Kalimuddin; Barnaby Edward Young; Yee‐Sin Leo; Cheng‐I Wang; Bernett Lee; Olaf Rötzschke; David Chien Lye; Laurent Renia; Lisa F.P. Ng. Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2. EMBO Molecular Medicine 2021, 13, e14045 .
AMA StyleYi‐Hao Chan, Siew‐Wai Fong, Chek‐Meng Poh, Guillaume Carissimo, Nicholas Kim‐Wah Yeo, Siti Naqiah Amrun, Yun Shan Goh, Jackwee Lim, Weili Xu, Rhonda Sin‐Ling Chee, Anthony Torres‐Ruesta, Cheryl Yi‐Pin Lee, Matthew Zirui Tay, Zi Wei Chang, Wen‐Hsin Lee, Bei Wang, Seow‐Yen Tan, Shirin Kalimuddin, Barnaby Edward Young, Yee‐Sin Leo, Cheng‐I Wang, Bernett Lee, Olaf Rötzschke, David Chien Lye, Laurent Renia, Lisa F.P. Ng. Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2. EMBO Molecular Medicine. 2021; 13 (6):e14045.
Chicago/Turabian StyleYi‐Hao Chan; Siew‐Wai Fong; Chek‐Meng Poh; Guillaume Carissimo; Nicholas Kim‐Wah Yeo; Siti Naqiah Amrun; Yun Shan Goh; Jackwee Lim; Weili Xu; Rhonda Sin‐Ling Chee; Anthony Torres‐Ruesta; Cheryl Yi‐Pin Lee; Matthew Zirui Tay; Zi Wei Chang; Wen‐Hsin Lee; Bei Wang; Seow‐Yen Tan; Shirin Kalimuddin; Barnaby Edward Young; Yee‐Sin Leo; Cheng‐I Wang; Bernett Lee; Olaf Rötzschke; David Chien Lye; Laurent Renia; Lisa F.P. Ng. 2021. "Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2." EMBO Molecular Medicine 13, no. 6: e14045.
PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.
Yun Shan Goh; Siew-Wai Fong; Siti Naqiah Amrun; Cheryl Lee; Pei Xiang Hor; Barnaby Young; Po Ying Chia; Paul Tambyah; Shirin Kalimuddin; Surinder Pada; Seow-Yen Tan; Louisa Sun; Mark Chen; Yee-Sin Leo; David Lye; Lisa Ng; Laurent Renia. Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease. 2021, 1 .
AMA StyleYun Shan Goh, Siew-Wai Fong, Siti Naqiah Amrun, Cheryl Lee, Pei Xiang Hor, Barnaby Young, Po Ying Chia, Paul Tambyah, Shirin Kalimuddin, Surinder Pada, Seow-Yen Tan, Louisa Sun, Mark Chen, Yee-Sin Leo, David Lye, Lisa Ng, Laurent Renia. Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease. . 2021; ():1.
Chicago/Turabian StyleYun Shan Goh; Siew-Wai Fong; Siti Naqiah Amrun; Cheryl Lee; Pei Xiang Hor; Barnaby Young; Po Ying Chia; Paul Tambyah; Shirin Kalimuddin; Surinder Pada; Seow-Yen Tan; Louisa Sun; Mark Chen; Yee-Sin Leo; David Lye; Lisa Ng; Laurent Renia. 2021. "Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease." , no. : 1.
Summary Clinically important broadly reactive B cells evolve during multiple infections, with B cells re-activated after secondary infection differing from B cells activated after a primary infection. Here we studied CD27highCD38high plasmablasts from patients with a primary or secondary dengue virus infection. Three transcriptionally and functionally distinct clusters were identified. The largest cluster 0/1 was plasma cell-related, with cells coding for serotype cross-reactive antibodies of the IgG1 isotype, consistent with memory B cell activation during an extrafollicular response. Cells in clusters 2 and 3 expressed low levels of antibody genes and high levels of genes associated with oxidative phosphorylation, EIF2 pathway, and mitochondrial dysfunction. Clusters 2 and 3 showed a transcriptional footprint of T cell help, in line with activation from naive B cells or memory B cells. Our results contribute to the understanding of the parallel B cell activation events that occur in humans after natural primary and secondary infection.
Angeline Rouers; Ramapraba Appanna; Marion Chevrier; Josephine Lum; Mai Chan Lau; Lingqiao Tan; Thomas Loy; Alicia Tay; Raman Sethi; Durgalakshmi Sathiakumar; Kaval Kaur; Julia Böhme; Yee-Sin Leo; Laurent Renia; Shanshan W. Howland; Amit Singhal; JinMiao Chen; Katja Fink. CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function. iScience 2021, 24, 102482 .
AMA StyleAngeline Rouers, Ramapraba Appanna, Marion Chevrier, Josephine Lum, Mai Chan Lau, Lingqiao Tan, Thomas Loy, Alicia Tay, Raman Sethi, Durgalakshmi Sathiakumar, Kaval Kaur, Julia Böhme, Yee-Sin Leo, Laurent Renia, Shanshan W. Howland, Amit Singhal, JinMiao Chen, Katja Fink. CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function. iScience. 2021; 24 (5):102482.
Chicago/Turabian StyleAngeline Rouers; Ramapraba Appanna; Marion Chevrier; Josephine Lum; Mai Chan Lau; Lingqiao Tan; Thomas Loy; Alicia Tay; Raman Sethi; Durgalakshmi Sathiakumar; Kaval Kaur; Julia Böhme; Yee-Sin Leo; Laurent Renia; Shanshan W. Howland; Amit Singhal; JinMiao Chen; Katja Fink. 2021. "CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function." iScience 24, no. 5: 102482.
Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.
Florence Wj Chioh; Siew-Wai Fong; Barnaby E Young; Kan-Xing Wu; Anthony Siau; Shuba Krishnan; Yi-Hao Chan; Guillaume Carissimo; Louis Ly Teo; Fei Gao; Ru San Tan; Liang Zhong; Angela S Koh; Seow-Yen Tan; Paul A Tambyah; Laurent Renia; Lisa Fp Ng; David C Lye; Christine Cheung. Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. eLife 2021, 10, 1 .
AMA StyleFlorence Wj Chioh, Siew-Wai Fong, Barnaby E Young, Kan-Xing Wu, Anthony Siau, Shuba Krishnan, Yi-Hao Chan, Guillaume Carissimo, Louis Ly Teo, Fei Gao, Ru San Tan, Liang Zhong, Angela S Koh, Seow-Yen Tan, Paul A Tambyah, Laurent Renia, Lisa Fp Ng, David C Lye, Christine Cheung. Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. eLife. 2021; 10 ():1.
Chicago/Turabian StyleFlorence Wj Chioh; Siew-Wai Fong; Barnaby E Young; Kan-Xing Wu; Anthony Siau; Shuba Krishnan; Yi-Hao Chan; Guillaume Carissimo; Louis Ly Teo; Fei Gao; Ru San Tan; Liang Zhong; Angela S Koh; Seow-Yen Tan; Paul A Tambyah; Laurent Renia; Lisa Fp Ng; David C Lye; Christine Cheung. 2021. "Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation." eLife 10, no. : 1.
Malaria begins when mosquito-borne Plasmodium sporozoites invade hepatocytes and usurp host pathways to support the differentiation and multiplication of erythrocyte-infective, merozoite progeny. All Plasmodium species encode an orthologue of the innate cytokine, Macrophage Migration Inhibitory Factor (MIF), which functions in mammalian biology to regulate innate responses. Using a genetically-targeted strain of Plasmodium berghei, we demonstrate that the Plasmodium MIF orthologue, PMIF, activates the cognate host MIF receptor, CD74, to inhibit the host-protective apoptosis response of infected hepatocytes and sustain Plasmodium development and replication. Infection of CD74 deficient (Cd74 −/− ) mice revealed a significantly reduced liver burden of Plasmodium parasites compared with WT mice and protection from experimental cerebral malaria (ECM) development. Protection from ECM additionally was associated with the inability of Cd74 −/− brain microvessel endothelial cells to present parasite antigen to sequestered, Plasmodium-specific CD8+ T cells. A novel pharmacologic PMIF-selective antagonist reduced PMIF/CD74 signaling and liver-stage parasite burden, and fully protected mice from ECM. These findings reveal a conserved mechanism for Plasmodium usurpation of host CD74 signaling and suggest a tractable approach for new pharmacologic intervention.
Alvaro Baeza Garcia; Edwin Siu; Xin Du; Lin Leng; Blandine Franke-Fayard; Chris J Janse; Shanshan W Howland; Laurent Rénia; Elias Lolis; Richard Bucala. Suppression of Plasmodium MIF-CD74 Signaling Protects Against Severe Malaria. 2021, 1 .
AMA StyleAlvaro Baeza Garcia, Edwin Siu, Xin Du, Lin Leng, Blandine Franke-Fayard, Chris J Janse, Shanshan W Howland, Laurent Rénia, Elias Lolis, Richard Bucala. Suppression of Plasmodium MIF-CD74 Signaling Protects Against Severe Malaria. . 2021; ():1.
Chicago/Turabian StyleAlvaro Baeza Garcia; Edwin Siu; Xin Du; Lin Leng; Blandine Franke-Fayard; Chris J Janse; Shanshan W Howland; Laurent Rénia; Elias Lolis; Richard Bucala. 2021. "Suppression of Plasmodium MIF-CD74 Signaling Protects Against Severe Malaria." , no. : 1.
Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.
Jackwee Lim; Kia Joo Puan; Liang Wei Wang; Karen Wei Weng Teng; Chiew Yee Loh; Kim Peng Tan; Guillaume Carissimo; Yi-Hao Chan; Chek Meng Poh; Cheryl Yi-Pin Lee; Siew-Wai Fong; Nicholas Kim-Wah Yeo; Rhonda Sin-Ling Chee; Siti Naqiah Amrun; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres-Ruesta; Norman Leo Fernandez; Wilson How; Anand K. Andiappan; Wendy Lee; Kaibo Duan; Seow-Yen Tan; Gabriel Yan; Shirin Kalimuddin; David Chien Lye; Yee-Sin Leo; Sean W. X. Ong; Barnaby E. Young; Laurent Renia; Lisa F.P. Ng; Bernett Lee; Olaf Rötzschke. Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response. 2021, 1 .
AMA StyleJackwee Lim, Kia Joo Puan, Liang Wei Wang, Karen Wei Weng Teng, Chiew Yee Loh, Kim Peng Tan, Guillaume Carissimo, Yi-Hao Chan, Chek Meng Poh, Cheryl Yi-Pin Lee, Siew-Wai Fong, Nicholas Kim-Wah Yeo, Rhonda Sin-Ling Chee, Siti Naqiah Amrun, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres-Ruesta, Norman Leo Fernandez, Wilson How, Anand K. Andiappan, Wendy Lee, Kaibo Duan, Seow-Yen Tan, Gabriel Yan, Shirin Kalimuddin, David Chien Lye, Yee-Sin Leo, Sean W. X. Ong, Barnaby E. Young, Laurent Renia, Lisa F.P. Ng, Bernett Lee, Olaf Rötzschke. Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response. . 2021; ():1.
Chicago/Turabian StyleJackwee Lim; Kia Joo Puan; Liang Wei Wang; Karen Wei Weng Teng; Chiew Yee Loh; Kim Peng Tan; Guillaume Carissimo; Yi-Hao Chan; Chek Meng Poh; Cheryl Yi-Pin Lee; Siew-Wai Fong; Nicholas Kim-Wah Yeo; Rhonda Sin-Ling Chee; Siti Naqiah Amrun; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres-Ruesta; Norman Leo Fernandez; Wilson How; Anand K. Andiappan; Wendy Lee; Kaibo Duan; Seow-Yen Tan; Gabriel Yan; Shirin Kalimuddin; David Chien Lye; Yee-Sin Leo; Sean W. X. Ong; Barnaby E. Young; Laurent Renia; Lisa F.P. Ng; Bernett Lee; Olaf Rötzschke. 2021. "Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response." , no. : 1.
Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.
Martin Windpessl; Annette Bruchfeld; Hans-Joachim Anders; Holly Kramer; Meryl Waldman; Laurent Renia; Lisa F. P. Ng; Zhou Xing; Andreas Kronbichler. COVID-19 vaccines and kidney disease. Nature Reviews Nephrology 2021, 17, 291 -293.
AMA StyleMartin Windpessl, Annette Bruchfeld, Hans-Joachim Anders, Holly Kramer, Meryl Waldman, Laurent Renia, Lisa F. P. Ng, Zhou Xing, Andreas Kronbichler. COVID-19 vaccines and kidney disease. Nature Reviews Nephrology. 2021; 17 (5):291-293.
Chicago/Turabian StyleMartin Windpessl; Annette Bruchfeld; Hans-Joachim Anders; Holly Kramer; Meryl Waldman; Laurent Renia; Lisa F. P. Ng; Zhou Xing; Andreas Kronbichler. 2021. "COVID-19 vaccines and kidney disease." Nature Reviews Nephrology 17, no. 5: 291-293.
Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations remain unknown. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate high Gas6 levels in the serum of patients with neurological complications which correlated with downregulation of genes associated with the type I IFN responses as consequence of Socs1 upregulation. Gas6 gamma-carboxylation is essential for ZIKV replication in monocytes, the main source of this protein. Gas6 also facilitates ZIKV replication in adult immunocompetent mice enabled susceptibility to transplacental infection and congenital malformations. Our data thus indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.
Joao Luiz Silva-Filho; Lilian Gomes De Oliveira; Leticia Monteiro; Pierina L. Parise; Nagela G. Zanluqui; Carolina M. Polonio; Carla Longo De Freitas; Daniel A. Toledo-Teixeira; William M. Souza; Najara Bittencourt; Mariene R. Amorim; Julia Forato; Stéfanie Primon Muraro; Gabriela Fabiano De Souza; Matheus Cavalheiro Martini; Karina Bispos-Dos-Santos; Carla C. Judice; Maria Laura Costa; Rodrigo N. Angerami; André R. R. Freitas; Mariangela R. Resende; Márcia T. Garcia; Maria Luiza Moretti; Laurent Renia; Lisa F. P. Ng; Carla V. Rothlin; Fabio Tm Costa; Jean Pierre Schatzmann Peron; José Luiz Proença-Modena; The Zika-Unicamp Network. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. 2021, 1 .
AMA StyleJoao Luiz Silva-Filho, Lilian Gomes De Oliveira, Leticia Monteiro, Pierina L. Parise, Nagela G. Zanluqui, Carolina M. Polonio, Carla Longo De Freitas, Daniel A. Toledo-Teixeira, William M. Souza, Najara Bittencourt, Mariene R. Amorim, Julia Forato, Stéfanie Primon Muraro, Gabriela Fabiano De Souza, Matheus Cavalheiro Martini, Karina Bispos-Dos-Santos, Carla C. Judice, Maria Laura Costa, Rodrigo N. Angerami, André R. R. Freitas, Mariangela R. Resende, Márcia T. Garcia, Maria Luiza Moretti, Laurent Renia, Lisa F. P. Ng, Carla V. Rothlin, Fabio Tm Costa, Jean Pierre Schatzmann Peron, José Luiz Proença-Modena, The Zika-Unicamp Network. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. . 2021; ():1.
Chicago/Turabian StyleJoao Luiz Silva-Filho; Lilian Gomes De Oliveira; Leticia Monteiro; Pierina L. Parise; Nagela G. Zanluqui; Carolina M. Polonio; Carla Longo De Freitas; Daniel A. Toledo-Teixeira; William M. Souza; Najara Bittencourt; Mariene R. Amorim; Julia Forato; Stéfanie Primon Muraro; Gabriela Fabiano De Souza; Matheus Cavalheiro Martini; Karina Bispos-Dos-Santos; Carla C. Judice; Maria Laura Costa; Rodrigo N. Angerami; André R. R. Freitas; Mariangela R. Resende; Márcia T. Garcia; Maria Luiza Moretti; Laurent Renia; Lisa F. P. Ng; Carla V. Rothlin; Fabio Tm Costa; Jean Pierre Schatzmann Peron; José Luiz Proença-Modena; The Zika-Unicamp Network. 2021. "Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice." , no. : 1.
Objectives The emergence of a SARS‐CoV‐2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross‐neutralise against the G614 variant. Methods Antibody profiling against the SARS‐CoV‐2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS‐CoV‐2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID‐19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). Results Profiling of the anti‐SARS‐CoV‐2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. Conclusions Cross‐reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS‐CoV‐2. More importantly, there should be negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed.
Cheryl Yi‐Pin Lee; Siti Naqiah Amrun; Rhonda Sin‐Ling Chee; Yun Shan Goh; Tze‐Minn Mak; Sophie Octavia; Nicholas Kim‐Wah Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres‐Ruesta; Guillaume Carissimo; Chek Meng Poh; Siew‐Wai Fong; Wang Bei; Sandy Lee; Barnaby Edward Young; Seow‐Yen Tan; Yee‐Sin Leo; David C Lye; Raymond Tp Lin; Sebastien Maurer‐Stroh; Bernett Lee; Cheng‐I Wang; Laurent Renia; Lisa Fp Ng. Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant. Clinical & Translational Immunology 2021, 10, e1241 .
AMA StyleCheryl Yi‐Pin Lee, Siti Naqiah Amrun, Rhonda Sin‐Ling Chee, Yun Shan Goh, Tze‐Minn Mak, Sophie Octavia, Nicholas Kim‐Wah Yeo, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres‐Ruesta, Guillaume Carissimo, Chek Meng Poh, Siew‐Wai Fong, Wang Bei, Sandy Lee, Barnaby Edward Young, Seow‐Yen Tan, Yee‐Sin Leo, David C Lye, Raymond Tp Lin, Sebastien Maurer‐Stroh, Bernett Lee, Cheng‐I Wang, Laurent Renia, Lisa Fp Ng. Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant. Clinical & Translational Immunology. 2021; 10 (2):e1241.
Chicago/Turabian StyleCheryl Yi‐Pin Lee; Siti Naqiah Amrun; Rhonda Sin‐Ling Chee; Yun Shan Goh; Tze‐Minn Mak; Sophie Octavia; Nicholas Kim‐Wah Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres‐Ruesta; Guillaume Carissimo; Chek Meng Poh; Siew‐Wai Fong; Wang Bei; Sandy Lee; Barnaby Edward Young; Seow‐Yen Tan; Yee‐Sin Leo; David C Lye; Raymond Tp Lin; Sebastien Maurer‐Stroh; Bernett Lee; Cheng‐I Wang; Laurent Renia; Lisa Fp Ng. 2021. "Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant." Clinical & Translational Immunology 10, no. 2: e1241.
In December 2019, a novel coronavirus was isolated from the respiratory epithelium of patients with unexplained pneumonia in Wuhan, China. This pathogen, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a pathogenic condition that has been termed coronavirus disease 2019 (COVID-19) and has reached pandemic proportions. As of 17 September 2020, more than 30 million confirmed SARS-CoV-2 infections have been reported in 204 different countries, claiming more than 1 million lives worldwide. Accumulating evidence suggests that SARS-CoV-2 infection can lead to a variety of clinical conditions, ranging from asymptomatic to life-threatening cases. In the early stages of the disease, most patients experience mild clinical symptoms, including a high fever and dry cough. However, 20% of patients rapidly progress to severe illness characterized by atypical interstitial bilateral pneumonia, acute respiratory distress syndrome and multiorgan dysfunction. Almost 10% of these critically ill patients subsequently die. Insights into the pathogenic mechanisms underlying SARS-CoV-2 infection and COVID-19 progression are emerging and highlight the critical role of the immunological hyper-response — characterized by widespread endothelial damage, complement-induced blood clotting and systemic microangiopathy — in disease exacerbation. These insights may aid the identification of new or existing therapeutic interventions to limit the progression of early disease and treat severe cases. This Review describes our current understanding of the pathogenic mechanisms involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the progression of coronavirus disease 2019 (COVID-19), focusing on the immunological hyper-response and the induction of widespread endothelial damage, complement-associated blood clotting and systemic microangiopathy, as well as the effects of these processes on the kidney. The authors also discuss therapeutic interventions that currently hold most promise.
Luca Perico; Ariela Benigni; Federica Casiraghi; Lisa F. P. Ng; Laurent Renia; Giuseppe Remuzzi. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nature Reviews Nephrology 2020, 17, 46 -64.
AMA StyleLuca Perico, Ariela Benigni, Federica Casiraghi, Lisa F. P. Ng, Laurent Renia, Giuseppe Remuzzi. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nature Reviews Nephrology. 2020; 17 (1):46-64.
Chicago/Turabian StyleLuca Perico; Ariela Benigni; Federica Casiraghi; Lisa F. P. Ng; Laurent Renia; Giuseppe Remuzzi. 2020. "Immunity, endothelial injury and complement-induced coagulopathy in COVID-19." Nature Reviews Nephrology 17, no. 1: 46-64.
SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.
Guillaume Carissimo; Weili Xu; Immanuel Kwok; Mohammad Yazid Abdad; Yi-Hao Chan; Siew-Wai Fong; Kia Joo Puan; Cheryl Yi-Pin Lee; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Wilson How; Stephrene Chan; Bingwen Eugene Fan; Anand Kumar Andiappan; Bernett Lee; Olaf Rötzschke; Barnaby Edward Young; Yee-Sin Leo; David Chien Lye; Laurent Renia; Lai Guan Ng; Anis Larbi; Lisa Fp Ng. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19. Nature Communications 2020, 11, 1 -12.
AMA StyleGuillaume Carissimo, Weili Xu, Immanuel Kwok, Mohammad Yazid Abdad, Yi-Hao Chan, Siew-Wai Fong, Kia Joo Puan, Cheryl Yi-Pin Lee, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Wilson How, Stephrene Chan, Bingwen Eugene Fan, Anand Kumar Andiappan, Bernett Lee, Olaf Rötzschke, Barnaby Edward Young, Yee-Sin Leo, David Chien Lye, Laurent Renia, Lai Guan Ng, Anis Larbi, Lisa Fp Ng. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19. Nature Communications. 2020; 11 (1):1-12.
Chicago/Turabian StyleGuillaume Carissimo; Weili Xu; Immanuel Kwok; Mohammad Yazid Abdad; Yi-Hao Chan; Siew-Wai Fong; Kia Joo Puan; Cheryl Yi-Pin Lee; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Wilson How; Stephrene Chan; Bingwen Eugene Fan; Anand Kumar Andiappan; Bernett Lee; Olaf Rötzschke; Barnaby Edward Young; Yee-Sin Leo; David Chien Lye; Laurent Renia; Lai Guan Ng; Anis Larbi; Lisa Fp Ng. 2020. "Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19." Nature Communications 11, no. 1: 1-12.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Sequencing the viral genome as the outbreak progresses is important, particularly in the identification of emerging isolates with different pathogenic potential and to identify whether nucleotide changes in the genome will impair clinical diagnostic tools such as real-time PCR assays. Although single nucleotide polymorphisms and point mutations occur during the replication of coronaviruses, one of the biggest drivers in genetic change is recombination. This can manifest itself in insertions and/or deletions in the viral genome. Therefore, sequencing strategies that underpin molecular epidemiology and inform virus biology in patients should take these factors into account. A long amplicon/read length-based RT-PCR sequencing approach focused on the Oxford Nanopore MinION/GridION platforms was developed to identify and sequence the SARS-CoV-2 genome in samples from patients with or suspected of COVID-19. The protocol, termed Rapid Sequencing Long Amplicons (RSLAs) used random primers to generate cDNA from RNA purified from a sample from a patient, followed by single or multiplex PCRs to generate longer amplicons of the viral genome. The base protocol was used to identify SARS-CoV-2 in a variety of clinical samples and proved sensitive in identifying viral RNA in samples from patients that had been declared negative using other nucleic acid-based assays (false negative). Sequencing the amplicons revealed that a number of patients had a proportion of viral genomes with deletions.
Shona C. Moore; Rebekah Penrice-Randall; Muhannad Alruwaili; Nadine Randle; Stuart Armstrong; Catherine Hartley; Sam Haldenby; Xiaofeng Dong; Abdulrahman Alrezaihi; Mai Almsaud; Eleanor Bentley; Jordan Clark; Isabel García-Dorival; Paul Gilmore; Ximeng Han; Benjamin Jones; Lisa Luu; Parul Sharma; Ghada Shawli; Yani Sun; Qin Zhao; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Jake Dunning; En-Min Zhou; Tom Solomon; Michael Beadsworth; James Cruise; Derrick W. Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard Vipond; Lisa Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; James Stewart; Alistair Darby; Malcolm Semple; Lance Turtle; Julian A. Hiscox. Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism. Viruses 2020, 12, 1164 .
AMA StyleShona C. Moore, Rebekah Penrice-Randall, Muhannad Alruwaili, Nadine Randle, Stuart Armstrong, Catherine Hartley, Sam Haldenby, Xiaofeng Dong, Abdulrahman Alrezaihi, Mai Almsaud, Eleanor Bentley, Jordan Clark, Isabel García-Dorival, Paul Gilmore, Ximeng Han, Benjamin Jones, Lisa Luu, Parul Sharma, Ghada Shawli, Yani Sun, Qin Zhao, Steven T. Pullan, Daniel P. Carter, Kevin Bewley, Jake Dunning, En-Min Zhou, Tom Solomon, Michael Beadsworth, James Cruise, Derrick W. Crook, David A. Matthews, Andrew D. Davidson, Zana Mahmood, Waleed Aljabr, Julian Druce, Richard Vipond, Lisa Ng, Laurent Renia, Peter J. M. Openshaw, J. Kenneth Baillie, Miles W. Carroll, James Stewart, Alistair Darby, Malcolm Semple, Lance Turtle, Julian A. Hiscox. Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism. Viruses. 2020; 12 (10):1164.
Chicago/Turabian StyleShona C. Moore; Rebekah Penrice-Randall; Muhannad Alruwaili; Nadine Randle; Stuart Armstrong; Catherine Hartley; Sam Haldenby; Xiaofeng Dong; Abdulrahman Alrezaihi; Mai Almsaud; Eleanor Bentley; Jordan Clark; Isabel García-Dorival; Paul Gilmore; Ximeng Han; Benjamin Jones; Lisa Luu; Parul Sharma; Ghada Shawli; Yani Sun; Qin Zhao; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Jake Dunning; En-Min Zhou; Tom Solomon; Michael Beadsworth; James Cruise; Derrick W. Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard Vipond; Lisa Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; James Stewart; Alistair Darby; Malcolm Semple; Lance Turtle; Julian A. Hiscox. 2020. "Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism." Viruses 12, no. 10: 1164.
The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions.
Cheryl Yi-Pin Lee; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Yun Shan Goh; Tze Minn Mak; Sophie Octavia; Nicholas Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres; Guillaume Carissimo; Chek Meng Poh; Siew-Wai Fong; Bei Wang; Sandy Lee; Barnaby Young; Seow Yen Tan; Yee Sin Leo; David Chien Boon Lye; Raymond Tp Lin; Sebastian Maurer-Stroh; Bernett T. K. Lee; Cheng-I Wang; Laurent Renia; Lisa F. P. Ng. Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant. 2020, 1 .
AMA StyleCheryl Yi-Pin Lee, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Yun Shan Goh, Tze Minn Mak, Sophie Octavia, Nicholas Yeo, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres, Guillaume Carissimo, Chek Meng Poh, Siew-Wai Fong, Bei Wang, Sandy Lee, Barnaby Young, Seow Yen Tan, Yee Sin Leo, David Chien Boon Lye, Raymond Tp Lin, Sebastian Maurer-Stroh, Bernett T. K. Lee, Cheng-I Wang, Laurent Renia, Lisa F. P. Ng. Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant. . 2020; ():1.
Chicago/Turabian StyleCheryl Yi-Pin Lee; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Yun Shan Goh; Tze Minn Mak; Sophie Octavia; Nicholas Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres; Guillaume Carissimo; Chek Meng Poh; Siew-Wai Fong; Bei Wang; Sandy Lee; Barnaby Young; Seow Yen Tan; Yee Sin Leo; David Chien Boon Lye; Raymond Tp Lin; Sebastian Maurer-Stroh; Bernett T. K. Lee; Cheng-I Wang; Laurent Renia; Lisa F. P. Ng. 2020. "Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant." , no. : 1.
In vitro antibody selection against pathogens from naïve combinatorial libraries can yield various classes of antigen-specific binders that are distinct from those evolved from natural infection1–4. Also, rapid neutralizing antibody discovery can be made possible by a strategy that selects for those interfering with pathogen and host interaction5. Here we report the discovery of antibodies that neutralize SARS-CoV-2, the virus responsible for the COVID-19 pandemic, from a highly diverse naïve human Fab library. Lead antibody 5A6 blocks the receptor binding domain (RBD) of the viral spike from binding to the host receptor angiotensin converting enzyme 2 (ACE2), neutralizes SARS-CoV-2 infection of Vero E6 cells, and reduces viral replication in reconstituted human nasal and bronchial epithelium models. 5A6 has a high occupancy on the viral surface and exerts its neutralization activity via a bivalent binding mode to the tip of two neighbouring RBDs at the ACE2 interaction interface, one in the “up” and the other in the “down” position, explaining its superior neutralization capacity. Furthermore, 5A6 is insensitive to several spike mutations identified in clinical isolates, including the D614G mutant that has become dominant worldwide. Our results suggest that 5A6 could be an effective prophylactic and therapeutic treatment of COVID-19.
Bei Wang; Daniel Asarnow; Wen-Hsin Lee; Ching-Wen Huang; Bryan Faust; Patricia Miang Lon Ng; Eve Zi Xian Ngoh; Markus Bohn; David Bulkley; Andrés Pizzorno; Hwee Ching Tan; Chia Yin Lee; Rabiatul Adawiyah Minhat; Olivier Terrier; Mun Kuen Soh; Frannie Jiuyi Teo; Yvonne Yee Chin Yeap; Yuanyu Hu; Shirley Gek Kheng Seah; Sebastian Maurer-Stroh; Laurent Renia; Brendon John Hanson; Manuel Rosa-Calatrava; Aashish Manglik; Yifan Cheng; Charles S. Craik; Cheng-I Wang. Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization. 2020, 1 .
AMA StyleBei Wang, Daniel Asarnow, Wen-Hsin Lee, Ching-Wen Huang, Bryan Faust, Patricia Miang Lon Ng, Eve Zi Xian Ngoh, Markus Bohn, David Bulkley, Andrés Pizzorno, Hwee Ching Tan, Chia Yin Lee, Rabiatul Adawiyah Minhat, Olivier Terrier, Mun Kuen Soh, Frannie Jiuyi Teo, Yvonne Yee Chin Yeap, Yuanyu Hu, Shirley Gek Kheng Seah, Sebastian Maurer-Stroh, Laurent Renia, Brendon John Hanson, Manuel Rosa-Calatrava, Aashish Manglik, Yifan Cheng, Charles S. Craik, Cheng-I Wang. Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization. . 2020; ():1.
Chicago/Turabian StyleBei Wang; Daniel Asarnow; Wen-Hsin Lee; Ching-Wen Huang; Bryan Faust; Patricia Miang Lon Ng; Eve Zi Xian Ngoh; Markus Bohn; David Bulkley; Andrés Pizzorno; Hwee Ching Tan; Chia Yin Lee; Rabiatul Adawiyah Minhat; Olivier Terrier; Mun Kuen Soh; Frannie Jiuyi Teo; Yvonne Yee Chin Yeap; Yuanyu Hu; Shirley Gek Kheng Seah; Sebastian Maurer-Stroh; Laurent Renia; Brendon John Hanson; Manuel Rosa-Calatrava; Aashish Manglik; Yifan Cheng; Charles S. Craik; Cheng-I Wang. 2020. "Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization." , no. : 1.