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1. Empirical and model-based evidence for a negligible role of cattle in peste des petits ruminants virus transmission and eradication

Author

Herzog, Catherine M., Aklilu, Fasil, Sibhatu, Demeke, Shegu, Dereje, Belaineh, Redeat, Mohammed, Abde Aliy, Kidane, Menbere, Schulz, Claudia, Willett, Brian J., Cleaveland, Sarah, Bailey, Dalan, Peters, Andrew R., Cattadori, Isabella M., Hudson, Peter J., Asgedom, Hagos, Buza, Joram, Forza, Mesfin Sahle, Chibssa, Tesfaye Rufael, Gebre, Solomon, Juleff, Nick, Bjørnstad, Ottar N., Baron, Michael D., and Kapur, Vivek

Published
2024
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3. Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

Author

Tan, Cedric C. S., Trew, Jahcub, Peacock, Thomas P., Mok, Kai Yi, Hart, Charlie, Lau, Kelvin, Ni, Dongchun, Orme, C. David L., Ransome, Emma, Pearse, William D., Coleman, Christopher M., Bailey, Dalan, Thakur, Nazia, Quantrill, Jessica L., Sukhova, Ksenia, Richard, Damien, Kahane, Laura, Woodward, Guy, Bell, Thomas, Worledge, Lisa, Nunez-Mino, Joe, Barclay, Wendy, van Dorp, Lucy, Balloux, Francois, and Savolainen, Vincent

Published
2023
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4. A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants

Author

Modhiran, Naphak, Lauer, Simon Malte, Amarilla, Alberto A., Hewins, Peter, Lopes van den Broek, Sara Irene, Low, Yu Shang, Thakur, Nazia, Liang, Benjamin, Nieto, Guillermo Valenzuela, Jung, James, Paramitha, Devina, Isaacs, Ariel, Sng, Julian D.J., Song, David, Jørgensen, Jesper Tranekjær, Cheuquemilla, Yorka, Bürger, Jörg, Andersen, Ida Vang, Himelreichs, Johanna, Jara, Ronald, MacLoughlin, Ronan, Miranda-Chacon, Zaray, Chana-Cuevas, Pedro, Kramer, Vasko, Spahn, Christian, Mielke, Thorsten, Khromykh, Alexander A., Munro, Trent, Jones, Martina L., Young, Paul R., Chappell, Keith, Bailey, Dalan, Kjaer, Andreas, Herth, Matthias Manfred, Jurado, Kellie Ann, Schwefel, David, Rojas-Fernandez, Alejandro, and Watterson, Daniel

Published
2023
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7. The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies

Author

Spencer, Alexandra J, Morris, Susan, Ulaszewska, Marta, Powers, Claire, Kailath, Reshma, Bissett, Cameron, Truby, Adam, Thakur, Nazia, Newman, Joseph, Allen, Elizabeth R, Rudiansyah, Indra, Liu, Chang, Dejnirattisai, Wanwisa, Mongkolsapaya, Juthathip, Davies, Hannah, Donnellan, Francesca R, Pulido, David, Peacock, Thomas P., Barclay, Wendy S., Bright, Helen, Ren, Kuishu, Screaton, Gavin, McTamney, Patrick, Bailey, Dalan, Gilbert, Sarah C, and Lambe, Teresa

Published
2022
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8. ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants

Author

van Doremalen, Neeltje, Schulz, Jonathan E., Adney, Danielle R., Saturday, Taylor A., Fischer, Robert J., Yinda, Claude Kwe, Thakur, Nazia, Newman, Joseph, Ulaszewska, Marta, Belij-Rammerstorfer, Sandra, Saturday, Greg, Spencer, Alexandra J., Bailey, Dalan, Russell, Colin A., Gilbert, Sarah C., Lambe, Teresa, and Munster, Vincent J.

Published
2022
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12. The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

Author

Zhuang, Xiaodong, Tsukuda, Senko, Wrensch, Florian, Wing, Peter A.C., Schilling, Mirjam, Harris, James M., Borrmann, Helene, Morgan, Sophie B., Cane, Jennifer L., Mailly, Laurent, Thakur, Nazia, Conceicao, Carina, Sanghani, Harshmeena, Heydmann, Laura, Bach, Charlotte, Ashton, Anna, Walsh, Steven, Tan, Tiong Kit, Schimanski, Lisa, Huang, Kuan-Ying A., Schuster, Catherine, Watashi, Koichi, Hinks, Timothy S.C., Jagannath, Aarti, Vausdevan, Sridhar R., Bailey, Dalan, Baumert, Thomas F., and McKeating, Jane A.

Published
2021
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13. A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

Author

Silva-Cayetano, Alyssa, Foster, William S., Innocentin, Silvia, Belij-Rammerstorfer, Sandra, Spencer, Alexandra J., Burton, Oliver T., Fra-Bidó, Sigrid, Le Lee, Jia, Thakur, Nazia, Conceicao, Carina, Wright, Daniel, Barrett, Jordan, Evans-Bailey, Nicola, Noble, Carly, Bailey, Dalan, Liston, Adrian, Gilbert, Sarah C., Lambe, Teresa, and Linterman, Michelle A.

Published
2021
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15. A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Author

Tan, Tiong Kit, Rijal, Pramila, Rahikainen, Rolle, Keeble, Anthony H., Schimanski, Lisa, Hussain, Saira, Harvey, Ruth, Hayes, Jack W. P., Edwards, Jane C., McLean, Rebecca K., Martini, Veronica, Pedrera, Miriam, Thakur, Nazia, Conceicao, Carina, Dietrich, Isabelle, Shelton, Holly, Ludi, Anna, Wilsden, Ginette, Browning, Clare, Zagrajek, Adrian K., Bialy, Dagmara, Bhat, Sushant, Stevenson-Leggett, Phoebe, Hollinghurst, Philippa, Tully, Matthew, Moffat, Katy, Chiu, Chris, Waters, Ryan, Gray, Ashley, Azhar, Mehreen, Mioulet, Valerie, Newman, Joseph, Asfor, Amin S., Burman, Alison, Crossley, Sylvia, Hammond, John A., Tchilian, Elma, Charleston, Bryan, Bailey, Dalan, Tuthill, Tobias J., Graham, Simon P., Duyvesteyn, Helen M. E., Malinauskas, Tomas, Huo, Jiandong, Tree, Julia A., Buttigieg, Karen R., Owens, Raymond J., Carroll, Miles W., Daniels, Rodney S., McCauley, John W., Stuart, David I., Huang, Kuan-Ying A., Howarth, Mark, and Townsend, Alain R.

Published
2021
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16. ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

Author

Lambe, Teresa, Spencer, Alexandra J., Thomas, Kelly M., Gooch, Karen E., Thomas, Stephen, White, Andrew D., Humphries, Holly E., Wright, Daniel, Belij-Rammerstorfer, Sandra, Thakur, Nazia, Conceicao, Carina, Watson, Robert, Alden, Leonie, Allen, Lauren, Aram, Marilyn, Bewley, Kevin R., Brunt, Emily, Brown, Phillip, Cavell, Breeze E., Cobb, Rebecca, Fotheringham, Susan A., Gilbride, Ciaran, Harris, Debbie J., Ho, Catherine M. K., Hunter, Laura, Kennard, Chelsea L., Leung, Stephanie, Lucas, Vanessa, Ngabo, Didier, Ryan, Kathryn A., Sharpe, Hannah, Sarfas, Charlotte, Sibley, Laura, Slack, Gillian S., Ulaszewska, Marta, Wand, Nadina, Wiblin, Nathan R., Gleeson, Fergus V., Bailey, Dalan, Sharpe, Sally, Charlton, Sue, Salguero, Francisco J., Carroll, Miles W., and Gilbert, Sarah C.

Published
2021
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19. Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression

Author

Zhuang, Xiaodong, primary, Gallo, Giulia, additional, Sharma, Parul, additional, Ha, Jiyeon, additional, Magri, Andrea, additional, Borrmann, Helene, additional, Harris, James M, additional, Tsukuda, Senko, additional, Bentley, Eleanor, additional, Kirby, Adam, additional, Neck, Simon de, additional, Yang, Hongbing, additional, Balfe, Peter, additional, Wing, Peter AC, additional, Matthews, David, additional, Harris, Adrian L, additional, Kipar, Anja, additional, Stewart, James P, additional, Bailey, Dalan, additional, and McKeating, Jane A, additional

Published
2023
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20. Development of reverse genetics for peste des petets ruminants virus (PPRV)

Author

Bailey, Dalan

Subjects
636.3089691
Abstract

Peste des petits ruminants virus (PPRV), a member of the Morbillivims genus in the family Paramyxoviridae, is the cause of a serious and emerging plague of small ruminants, mostly affecting sheep and goats. It is endemic in many developing countries in Africa and southern Asia and is highly contagious, with the mortality rate approaching 90% in some outbreaks. Development of reverse genetics systems for other morbilliviruses such as rinderpest and measles has allowed more focused research into replication, pathogenicity and marker vaccines.

Published
2006

21. Predicting the past and future evolutionary space of SARS-CoV-2

Author

Hiscox, Julian, primary, Dong, Xiaofeng, additional, Matthews, David, additional, Gallo, Giulia, additional, Darby, Alisdair, additional, Donovan-Banfield, I'ah, additional, Goldswain, Hannah, additional, MacGill, Tracy, additional, Myers, Todd, additional, Orr, Robert, additional, Bailey, Dalan, additional, and Carroll, Miles, additional

Published
2023
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22. Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Author

Graham, Simon P., McLean, Rebecca K., Spencer, Alexandra J., Belij-Rammerstorfer, Sandra, Wright, Daniel, Ulaszewska, Marta, Edwards, Jane C., Hayes, Jack W. P., Martini, Veronica, Thakur, Nazia, Conceicao, Carina, Dietrich, Isabelle, Shelton, Holly, Waters, Ryan, Ludi, Anna, Wilsden, Ginette, Browning, Clare, Bialy, Dagmara, Bhat, Sushant, Stevenson-Leggett, Phoebe, Hollinghurst, Philippa, Gilbride, Ciaran, Pulido, David, Moffat, Katy, Sharpe, Hannah, Allen, Elizabeth, Mioulet, Valerie, Chiu, Chris, Newman, Joseph, Asfor, Amin S., Burman, Alison, Crossley, Sylvia, Huo, Jiandong, Owens, Raymond J., Carroll, Miles, Hammond, John A., Tchilian, Elma, Bailey, Dalan, Charleston, Bryan, Gilbert, Sarah C., Tuthill, Tobias J., and Lambe, Teresa

Published
2020
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23. ChAdOx1 nCoV‐19 vaccination generates spike‐specific CD8 + T cells in aged mice

Author

Foster, William S, primary, Newman, Joseph, additional, Thakur, Nazia, additional, Spencer, Alexandra J, additional, Davies, Sophie, additional, Woods, Danielle, additional, Godfrey, Leila, additional, Ross, Sarah H, additional, Sharpe, Hayley J, additional, Richard, Arianne C, additional, Bailey, Dalan, additional, Lambe, Teresa, additional, and Linterman, Michelle A, additional

Published
2023
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25. Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway

Author

Benedikz, Elizabeth K., Bailey, Dalan, Cook, Charlotte N. L., Gonçalves-Carneiro, Daniel, Buckner, Michelle M. C., Blair, Jessica M. A., Wells, Timothy J., Fletcher, Nicola F., Goodall, Margaret, Flores-Langarica, Adriana, Kingsley, Robert A., Madsen, Jens, Teeling, Jessica, Johnston, Sebastian L., MacLennan, Calman A., Balfe, Peter, Henderson, Ian R., Piddock, Laura J. V., Cunningham, Adam F., and McKeating, Jane A.

Published
2019
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26. ChAdOx1 nCoV-19 vaccination generates spike-specific CD8+ T cells in aged mice

Author

Foster, William, primary, Thakur, Nazia, additional, Newman, Joseph, additional, Spencer, Alexandra, additional, Woods, Danielle, additional, Godfrey, Leila, additional, Ross, Sarah, additional, Richard, Arianne, additional, Sharpe, Hayley, additional, Bailey, Dalan, additional, Lambe, Teresa, additional, and Linterman, Michelle, additional

Published
2023
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27. Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

Author

Tan, Cedric C.S., primary, Trew, Jahcub, additional, Peacock, Thomas P., additional, Mok, Kai Yi, additional, Hart, Charlie, additional, Lau, Kelvin, additional, Ni, Dongchun, additional, Orme, David, additional, Ransome, Emma, additional, Pearse, William D., additional, Coleman, Christopher M., additional, Bailey, Dalan, additional, Thakur, Nazia, additional, Quantrill, Jessica L., additional, Sukhova, Ksenia, additional, Richard, Damien, additional, Woodward, Guy, additional, Bell, Thomas, additional, Worledge, Lisa, additional, Nunez-Mino, Joe, additional, Barclay, Wendy, additional, van Dorp, Lucy, additional, Balloux, Francois, additional, and Savolainen, Vincent, additional

Published
2023
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28. Study Design and Operation for Evaluating Nipah Virus Vaccine Candidates Among Backyard Pigs of Indigenous Communities in Bangladesh

Author

Rahman, Mustafizur, Shanta, Ireen Sultana, McLean, Rebecca, Siddika, Ayesha, Begum, Mst. Noorjahan, Rahman, Md Sezanur, Bhuyan, Abdulla, Thakur, Nazia, Bailey, Dalan, Chappell, Keith, Isaacs, Ariel, Watterson, Daniel, Alam, Muntasir, Hassan, Mahdi, Rahman, Mohammed Ziaur, Lambe, T, Gilbert, Sarah C, Young, Paul, and Graham, Simon

Abstract

Background: Nipah virus (NiV) causes a severe and often fatal neurological disease in humans. Although only bats were identified to cause NiV outbreaks in Bangladesh, direct pig-to-human transmission of NiV was responsible for outbreaks in Malaysia and Singapore during 1998-99. Despite the threat, both in animals and humans, no licensed vaccines are currently available. To address this gap, we aim to evaluate the immunogenicity of three NiV vaccine candidates in pigs under field conditions in Bangladesh. Methods: From January-August 2021, we enrolled 7 indigenous communities/villages and carried out community mobilization and engagement activities through interactive discussions . Subsequently, we blood sampled 60 randomly selected pigs and examined the presence of NiV G and F specific antibodies by ELISA. The NiV antibody-negative 45 pigs were immunized with three NiV vaccine candidates: (1) an adjuvanted NiV sG protein; (2) NiV G protein delivered by a replication-deficient simian adenoviral vector (ChAdOx1 NiV G); and (3) an adjuvanted, molecular clamp stabilized NiV F (mcsF) protein. We followed up the pigs for any adverse effects and collected blood samples on day 14, day 28 and day 42 to test both humoral and cellular immunogenicity. Results: We identified that 63% (143/238) households raised pigs as free scavenging livestock in the selected villages. Among the 60 pigs that selected for NiV antibody testing, the mean and median age was 6 months; 16 were female. To analyze the ELISA test positivity for NiV antibodies, we used a standard arbitrary threshold of 4 x the OD of the negative sera. We did not detect any NiV G or F reactive responses in the enrolled pigs. No adverse effects were observed among immunized pigs. Collected blood samples in different time points were stored at icddr,b biorepository for future laboratory investigation to determine T cell IFN-γ responses, NiV-neutralizing antibody (nAb) titers, and NiV antigen-specific Ab ELISA titers. Conclusion: The absence of antibodies against NiV G/F in pigs should be interpreted cautiously due to the relatively small sample size and single-location investigation. The impending findings of this study will provide a platform and strategy for developing NiV vaccine(s) not only for animals but also for humans.

Published
2023
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29. An alpaca-derived nanobody recognizes a unique conserved epitope and retains potent activity against the SARS-CoV-2 omicron variant

Author

Modhiran, Naphak, primary, Lauer, Simon Malte, additional, Amarilla, Alberto A, additional, Hewins, Peter, additional, van den Broek, Sara Irene Lopes, additional, Low, Yu Shang, additional, Thakur, Nazia, additional, Liang, Benjamin, additional, Nieto, Guillermo Valenzuela, additional, Jung, James, additional, Paramitha, Devina, additional, Isaacs, Ariel, additional, de Sng, Julian, additional, Song, David, additional, Jørgensen, Jesper Tranekjær, additional, Cheuquemilla, Yorka, additional, Bürger, Jörg, additional, Andersen, Ida Vang, additional, Himelreichs, Johanna, additional, Jara, Ronald, additional, MacLoughlin, Ronan, additional, Miranda-Chacon, Zaray, additional, Chana-Cuevas, Pedro, additional, Kramer, Vasko, additional, Spahn, Christian M.T., additional, Mielke, Thorsten, additional, Khromykh, Alexander A, additional, Munro, Trent, additional, Jones, Martina, additional, Young, Paul R, additional, Chappell, Keith, additional, Bailey, Dalan, additional, Kjaer, Andreas, additional, Herth, Matthias Manfred, additional, Jurado, Kellie Ann, additional, Schwefel, David, additional, Rojas-Fernandez, Alejandro, additional, and Watterson, Daniel, additional

Published
2022
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30. ChAdOx1 nCoV‐19 vaccination generates spike‐specific CD8+ T cells in aged mice.

Author

Foster, William S, Newman, Joseph, Thakur, Nazia, Spencer, Alexandra J, Davies, Sophie, Woods, Danielle, Godfrey, Leila, Ross, Sarah H, Sharpe, Hayley J, Richard, Arianne C, Bailey, Dalan, Lambe, Teresa, and Linterman, Michelle A

Subjects
T cells, SARS-CoV-2, CYTOTOXIC T cells, OLDER people, VACCINATION
Abstract

Effective vaccines have reduced the morbidity and mortality caused by severe acute respiratory syndrome coronavirus‐2 infection; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8+ T cells are important for killing virally infected cells, and vaccines that induce antigen‐specific CD8+ T cells in addition to humoral immunity provide an extra layer of immune protection. This is particularly important in cases where antibody titers are suboptimal, as can occur in older individuals. Here, we show that in aged mice, spike epitope–specific CD8+ T cells are generated in comparable numbers to younger animals after ChAdOx1 nCoV‐19 vaccination, although phenotypic differences exist. This demonstrates that ChAdOx1 nCoV‐19 elicits a good CD8+ T‐cell response in older bodies, but that typical age‐associated features are evident on these vaccine reactive T cells. [ABSTRACT FROM AUTHOR]

Published
2023
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31. A platform technology for generating subunit vaccines against diverse viral pathogens

Author

Young, Andrew, primary, Isaacs, Ariel, additional, Scott, Connor A. P., additional, Modhiran, Naphak, additional, McMillan, Christopher L. D., additional, Cheung, Stacey T. M., additional, Barr, Jennifer, additional, Marsh, Glenn, additional, Thakur, Nazia, additional, Bailey, Dalan, additional, Li, Kenneth S. M., additional, Luk, Hayes K. H., additional, Kok, Kin-Hang, additional, Lau, Susanna K. P., additional, Woo, Patrick C. Y., additional, Furuyama, Wakako, additional, Marzi, Andrea, additional, Young, Paul R., additional, Chappell, Keith J., additional, and Watterson, Daniel, additional

Published
2022
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32. An entropic safety catch controls hepatitis C virus entry and antibody resistance

Author

Stejskal, Lenka, primary, Kalemera, Mphatso D, primary, Lewis, Charlotte B, additional, Palor, Machaela, additional, Walker, Lucas, additional, Daviter, Tina, additional, Lees, William D, additional, Moss, David S, additional, Kremyda-Vlachou, Myrto, additional, Kozlakidis, Zisis, additional, Gallo, Giulia, additional, Bailey, Dalan, additional, Rosenberg, William, additional, Illingworth, Christopher JR, additional, Shepherd, Adrian J, additional, and Grove, Joe, additional

Published
2022
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33. An entropic safety catch controls hepatitis C virus entry and antibody resistance

Author

Stejskal, Lenka, Kalemera, Mphatso D., Lewis, Charlotte B., Palor, Machaela, Walker, Lucas, Daviter, Tina, Lees, William D., Moss, David S., Kremyda-Vlachou, Myrto, Kozlakidis, Zisis, Gallo, Giulia, Bailey, Dalan, Rosenberg, William, Illingworth, Christopher J. R., Shepherd, Adrian J., Grove, Joe, Stejskal, Lenka, Kalemera, Mphatso D., Lewis, Charlotte B., Palor, Machaela, Walker, Lucas, Daviter, Tina, Lees, William D., Moss, David S., Kremyda-Vlachou, Myrto, Kozlakidis, Zisis, Gallo, Giulia, Bailey, Dalan, Rosenberg, William, Illingworth, Christopher J. R., Shepherd, Adrian J., and Grove, Joe

Abstract

E1 and E2 (E1E2), the fusion proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Thus, HVR-1 is akin to a safety catch that prevents premature triggering of E1E2 activity. Crucially, this mechanism is turned off by host receptor interactions at the cell surface to allow entry. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies. This discovery provides an explanation for the ability of HCV to persist in the face of continual immune assault and represents a novel regulatory mechanism that is likely to be found in other viral fusion machinery.

Published
2022

34. Differential susceptibility of SARS-CoV-2 in animals : Evidence of ACE2 host receptor distribution in companion animals, livestock and wildlife by immunohistochemical characterisation

Author

Lean, Fabian Z.X., Núñez, Alejandro, Spiro, Simon, Priestnall, Simon L., Vreman, Sandra, Bailey, Dalan, James, Joe, Wrigglesworth, Ethan, Suarez-Bonnet, Alejandro, Conceicao, Carina, Thakur, Nazia, Byrne, Alexander M.P., Ackroyd, Stuart, Delahay, Richard J., van der Poel, Wim H.M., Brown, Ian H., Fooks, Anthony R., Brookes, Sharon M., Lean, Fabian Z.X., Núñez, Alejandro, Spiro, Simon, Priestnall, Simon L., Vreman, Sandra, Bailey, Dalan, James, Joe, Wrigglesworth, Ethan, Suarez-Bonnet, Alejandro, Conceicao, Carina, Thakur, Nazia, Byrne, Alexander M.P., Ackroyd, Stuart, Delahay, Richard J., van der Poel, Wim H.M., Brown, Ian H., Fooks, Anthony R., and Brookes, Sharon M.

Abstract

Angiotensin converting enzyme 2 (ACE2) is a host cell membrane protein (receptor) that mediates the binding of coronavirus, most notably SARS coronaviruses in the respiratory and gastrointestinal tracts. Although SARS-CoV-2 infection is mainly confined to humans, there have been numerous incidents of spillback (reverse zoonoses) to domestic and captive animals. An absence of information on the spatial distribution of ACE2 in animal tissues limits our understanding of host species susceptibility. Here, we describe the distribution of ACE2 using immunohistochemistry (IHC) on histological sections derived from carnivores, ungulates, primates and chiroptera. Comparison of mink (Neovison vison) and ferret (Mustela putorius furo) respiratory tracts showed substantial differences, demonstrating that ACE2 is present in the lower respiratory tract of mink but not ferrets. The presence of ACE2 in the respiratory tract in some species was much more restricted as indicated by limited immunolabelling in the nasal turbinate, trachea and lungs of cats (Felis catus) and only the nasal turbinate in the golden Syrian hamster (Mesocricetus auratus). In the lungs of other species, ACE2 could be detected on the bronchiolar epithelium of the sheep (Ovis aries), cattle (Bos taurus), European badger (Meles meles), cheetah (Acinonyx jubatus), tiger and lion (Panthera spp.). In addition, ACE2 was present in the nasal mucosa epithelium of the serotine bat (Eptesicus serotinus) but not in pig (Sus scrofa domestica), cattle or sheep. In the intestine, ACE2 immunolabelling was seen on the microvillus of enterocytes (surface of intestine) across various taxa. These results provide anatomical evidence of ACE2 expression in a number of species which will enable further understanding of host susceptibility and tissue tropism of ACE2 receptor-mediated viral infection.

Published
2022

36. An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity.

Author

Wing, Peter AC, Schmidt, Nathalie M., Peters, Rory, Erdmann, Maximilian, Brown, Rachel, Wang, Hao, Swadling, Leo, Newman, Joseph, Thakur, Nazia, Shionoya, Kaho, Morgan, Sophie B., Hinks, Timothy SC, Watashi, Koichi, Bailey, Dalan, Hansen, Scott B., Davidson, Andrew D., Maini, Mala K., and McKeating, Jane A.

Subjects
SARS-CoV-2, LIFE cycles (Biology), LIPID rafts, COVID-19 treatment, CELL physiology, T cells, CHOLESTEROL metabolism, T cell receptors
Abstract

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314. Author summary: Cholesterol metabolism is a key element in both viral replication and immune cell signalling. We show that Avasimibe, an inhibitor of the cholesterol esterification enzyme Acyl-CoA:cholesterol acyltransferase (ACAT), potently inhibits SARS-CoV-2 entry and viral RNA replication. Importantly, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells isolated from the blood of patients sampled during the acute phase of infection. Our findings show that Avasimibe has combined antiviral and T cell boosting properties in acute SARS-CoV-2 infection. This study reinforces an emerging picture of the importance of cholesterol metabolism in viral replication and T cell immunity, providing new insights on intrinsic anti-viral pathways that may be applicable to other viral pathogens. [ABSTRACT FROM AUTHOR]

Published
2023
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38. Author response: An entropic safety catch controls hepatitis C virus entry and antibody resistance

Author

Stejskal, Lenka, primary, Kalemera, Mphatso D, primary, Lewis, Charlotte B, additional, Palor, Machaela, additional, Walker, Lucas, additional, Daviter, Tina, additional, Lees, William D, additional, Moss, David S, additional, Kremyda-Vlachou, Myrto, additional, Kozlakidis, Zisis, additional, Gallo, Giulia, additional, Bailey, Dalan, additional, Rosenberg, William, additional, Illingworth, Christopher JR, additional, Shepherd, Adrian J, additional, and Grove, Joe, additional

Published
2022
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39. SARS-CoV-2 Spike has broad tropism for mammalian ACE2 proteins yet exhibits a distinct pattern of receptor usage when compared to other β-coronavirus Spike proteins

Author

Conceicao*, Carina, primary, Thakur*, Nazia, additional, Human, Stacey, additional, Kelly, James T, additional, Logan, Leanne, additional, Bialy, Dagmara, additional, Bhat, Sushant, additional, Stevenson-Leggett, Phoebe, additional, Zagrajek, Adrian K, additional, Hollinghurst, Philippa, additional, Varga, Michal, additional, Tsirigoti, Christina, additional, Tully, Matthew, additional, Chiu, Chris, additional, Moffat, Katy, additional, Silesian, Adrian Paul, additional, Hammond, John A, additional, Maier, Helena J, additional, Bickerton, Erica, additional, Shelton, Holly, additional, Dietrich, Isabelle, additional, Graham, Stephen C, additional, and Bailey, Dalan, additional

Published
2022
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40. Distinct antigenic properties of the SARS-CoV-2 Omicron lineages BA.4 and BA.5

Author

Willett, Brian J., primary, Kurshan, Ashwini, additional, Thakur, Nazia, additional, Newman, Joseph, additional, Manali, Maria, additional, Tyson, Grace, additional, Logan, Nicola, additional, Murcia, Pablo R., additional, Snell, Luke B., additional, Edgeworth, Jonathan D., additional, Zhou, Jie, additional, Sukhova, Ksenia, additional, Amirthalingam, Gayatri, additional, Brown, Kevin, additional, Charleston, Bryan, additional, Malim, Michael H., additional, Thomson, Emma C., additional, Barclay, Wendy S., additional, Bailey, Dalan, additional, Doores, Katie J., additional, and Peacock, Thomas P., additional

Published
2022
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42. Porcine Respiratory Coronavirus as a Model for Acute Respiratory Coronavirus Disease

Author

Keep, Sarah, primary, Carr, Brigid Veronica, additional, Lean, Fabian Z. X., additional, Fones, Albert, additional, Newman, Joseph, additional, Dowgier, Giulia, additional, Freimanis, Graham, additional, Vatzia, Eleni, additional, Polo, Noemi, additional, Everest, Holly, additional, Webb, Isobel, additional, Mcnee, Adam, additional, Paudyal, Basu, additional, Thakur, Nazia, additional, Nunez, Alejandro, additional, MacLoughlin, Ronan, additional, Maier, Helena, additional, Hammond, John, additional, Bailey, Dalan, additional, Waters, Ryan, additional, Charleston, Bryan, additional, Tuthill, Toby, additional, Britton, Paul, additional, Bickerton, Erica, additional, and Tchilian, Elma, additional

Published
2022
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43. Efficacy of ChAdOx1 vaccines against SARS-CoV-2 Variants of Concern Beta, Delta and Omicron in the Syrian hamster model

Author

Doremalen, Neeltje van, primary, Schulz, Jonathan E., additional, Adney, Danielle R., additional, Saturday, Taylor A., additional, Fischer, Robert J., additional, Yinda, Claude Kwe, additional, Thakur, Nazia, additional, Newman, Joseph, additional, Ulaszewska, Marta, additional, Belij-Rammerstorfer, Sandra, additional, Saturday, Greg, additional, Spencer, Alexandra J., additional, Bailey, Dalan, additional, Gilbert, Sarah C., additional, Lambe, Teresa, additional, and Munster, Vincent J., additional

Published
2022
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45. Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway

Author

Zhou, Jie, primary, Peacock, Thomas P., additional, Brown, Jonathan C., additional, Goldhill, Daniel H., additional, Elrefaey, Ahmed M.E., additional, Penrice-Randal, Rebekah, additional, Cowton, Vanessa M., additional, De Lorenzo, Giuditta, additional, Furnon, Wilhelm, additional, Harvey, William T., additional, Kugathasan, Ruthiran, additional, Frise, Rebecca, additional, Baillon, Laury, additional, Lassaunière, Ria, additional, Thakur, Nazia, additional, Gallo, Giulia, additional, Goldswain, Hannah, additional, Donovan-Banfield, I'ah, additional, Dong, Xiaofeng, additional, Randle, Nadine P., additional, Sweeney, Fiachra, additional, Glynn, Martha C., additional, Quantrill, Jessica L., additional, McKay, Paul F., additional, Patel, Arvind H., additional, Palmarini, Massimo, additional, Hiscox, Julian A., additional, Bailey, Dalan, additional, and Barclay, Wendy S., additional

Published
2022
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46. The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

Author

Peacock, Thomas P., primary, Brown, Jonathan C., additional, Zhou, Jie, additional, Thakur, Nazia, additional, Sukhova, Ksenia, additional, Newman, Joseph, additional, Kugathasan, Ruthiran, additional, Yan, Ada W.C., additional, Furnon, Wilhelm, additional, De Lorenzo, Giuditta, additional, Cowton, Vanessa M., additional, Reuss, Dorothee, additional, Moshe, Maya, additional, Quantrill, Jessica L., additional, Platt, Olivia K., additional, Kaforou, Myrsini, additional, Patel, Arvind H., additional, Palmarini, Massimo, additional, Bailey, Dalan, additional, and Barclay, Wendy S., additional

Published
2022
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48. Neutralising antibody activity against SARS-CoV-2 variants, including Omicron, in an elderly cohort vaccinated with BNT162b2

Author

Newman, Joseph, primary, Thakur, Nazia, additional, Peacock, Thomas P., additional, Bialy, Dagmara, additional, Elreafey, Ahmed ME, additional, Bogaardt, Carlijn, additional, Horton, Daniel L., additional, Ho, Sammy, additional, Kankeyan, Thivya, additional, Carr, Christine, additional, Hoschler, Katja, additional, Barclay, Wendy S., additional, Amirthalingam, Gayatri, additional, Brown, Kevin, additional, Charleston, Bryan, additional, and Bailey, Dalan, additional

Published
2021
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50. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Author

Meng, Bo, Kemp, Steven A, Papa, Guido, Datir, Rawlings, Ferreira, Isabella ATM, Marelli, Sara, Harvey, William T, Lytras, Spyros, Mohamed, Ahmed, Gallo, Giulia, Thakur, Nazia, Collier, Dami A, Mlcochova, Petra, COVID-19 Genomics UK (COG-UK) Consortium, Duncan, Lidia M, Carabelli, Alessandro M, Kenyon, Julia C, Lever, Andrew M, De Marco, Anna, Saliba, Christian, Culap, Katja, Cameroni, Elisabetta, Matheson, Nicholas J, Piccoli, Luca, Corti, Davide, James, Leo C, Robertson, David L, Bailey, Dalan, Gupta, Ravindra K, Kemp, Steven [0000-0001-7077-6793], Datir, Rawlings [0000-0003-0521-2144], Mlcochova, Petra [0000-0001-6908-9363], Carabelli, Alessandro [0000-0003-3625-4021], Matheson, Nicholas [0000-0002-3318-1851], Gupta, Ravindra [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
Medical Physiology, Antibodies, Viral, Antibodies, Cell Line, resistance, COVID-19 Genomics UK (COG-UK) Consortium, Recurrence, spike mutation, Chlorocebus aethiops, Animals, Humans, neutralizing antibodies, Viral, deletion, B.1.1.7, Neutralizing, Lung, Pandemics, Vero Cells, Phylogeny, Immune Evasion, SARS-CoV-2, infectivity, COVID-19, Pneumonia, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus, body regions, Infectious Diseases, Emerging Infectious Diseases, Good Health and Well Being, HEK293 Cells, Alpha variant, Mutation, Spike Glycoprotein, Coronavirus, antibody escape, Biochemistry and Cell Biology, Protein Binding
Abstract

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. Invitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Published
2021

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