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1. Widespread human exposure to ledanteviruses in Uganda: A population study.

Author

James G Shepherd, Shirin Ashraf, Jesus F Salazar-Gonzalez, Maria G Salazar, Robert G Downing, Henry Bukenya, Hanna Jerome, Joseph T Mpanga, Chris Davis, Lily Tong, Vattipally B Sreenu, Linda A Atiku, Nicola Logan, Ezekiel Kajik, Yafesi Mukobi, Cyrus Mungujakisa, Michael V Olowo, Emmanuel Tibo, Fred Wunna, Hollie Jackson Ireland, Andrew E Blunsum, Iyanuoluwani Owolabi, Ana da Silva Filipe, Josephine Bwogi, Brian J Willett, Julius J Lutwama, Daniel G Streicker, Pontiano Kaleebu, and Emma C Thomson

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda.

Published
2024
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2. Enhancement of Omicron-specific immune responses following bivalent COVID-19 booster vaccination in patients with chronic lymphocytic leukaemia

Author

Thomas Roberts, Grace Uwenedi, Rachel Bruton, Graham McIlroy, Sarah Damery, Panagiota Sylla, Nicola Logan, Sam Scott, May Lau, Ahmed Elzaidi, Siobhan Plass, Soumyajit Mallick, Katie Spencer, Christine Stephens, Christopher Bentley, Guy Pratt, Jianmin Zuo, Shankara Paneesha, Brian Willett, Paul Moss, and Helen Parry

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2024
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3. SARS-CoV-2 Seroprevalence and Cross-Variant Antibody Neutralization in Cats, United Kingdom

Author

Grace B. Tyson, Sarah Jones, Nicola Logan, Michael McDonald, Leigh Marshall, Pablo R. Murcia, Brian J. Willett, William Weir, and Margaret J. Hosie

Subjects
COVID-19, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, viruses, respiratory infections, zoonoses, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021–February 2022. The variant-specific response in cats trailed circulating variants in humans, indicating multiple human-to-cat transmissions over a prolonged period.

Published
2023
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4. Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion

Author

Nicola Logan, David Wright, Rebecca J Brownlie, Robert J Salmond, Rose Zamoyska, Alexandra Rose Teagle, Patricia Castro-Sanchez, and Simran S Kapoor

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell antitumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTLs) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion.Methods Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic restimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout.Results Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Antitumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL.Conclusions This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short-term augmented effector function against the risk of T cell exhaustion in order to achieve longer-term protection.

Published
2023
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5. Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysisResearch in context

Author

Christopher A. Martin, Joshua Nazareth, Amar Jarkhi, Daniel Pan, Mrinal Das, Nicola Logan, Sam Scott, Luke Bryant, Neha Abeywickrama, Oluwatobi Adeoye, Aleem Ahmed, Aqua Asif, Srini Bandi, Nisha George, Marjan Gohar, Laura J. Gray, Ross Kaszuba, Jitendra Mangwani, Marianne Martin, Arumugam Moorthy, Valerie Renals, Lucy Teece, Denny Vail, Kamlesh Khunti, Paul Moss, Andrea Tattersall, Bassam Hallis, Ashley D. Otter, Cathy Rowe, Brian J. Willett, Pranab Haldar, Andrea Cooper, and Manish Pareek

Subjects
SARS-CoV-2, COVID-19, Vaccine, Ethnicity, Heathcare worker, Medicine (General), R5-920
Abstract

Summary: Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06–2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05–2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178–12,852] vs 5888 BAU/ml [5023–6902], P = 0.008 and 2851 95% CI [1811–4487] vs 1199 [984–1462], P

Published
2023
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6. Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia

Author

Helen Parry, Graham McIlroy, Rachel Bruton, Sarah Damery, Grace Tyson, Nicola Logan, Chris Davis, Brian Willett, Jianmin Zuo, Myah Ali, Manjit Kaur, Christine Stephens, Dawn Brant, Ashley Otter, Tina McSkeane, Hayley Rolfe, Sian Faustini, Alex Richter, Sophie Lee, Farooq Wandroo, Salim Shafeek, Guy Pratt, Shankara Paneesha, and Paul Moss

Subjects
Vaccination, CLL, Leukaemia, SARS-CoV-2, COVID, Antibody, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. Method We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. Results Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. Conclusions These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.

Published
2022
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7. SARS-CoV-2 in Domestic UK Cats from Alpha to Omicron: Swab Surveillance and Case Reports

Author

Sarah Jones, Grace B. Tyson, Richard J. Orton, Katherine Smollett, Federica Manna, Kirsty Kwok, Nicolás M. Suárez, Nicola Logan, Michael McDonald, Andrea Bowie, Ana Da Silva Filipe, Brian J. Willett, William Weir, and Margaret J. Hosie

Subjects
SARS-CoV-2, COVID-19, coronavirus, pets, companion animals, reverse zoonosis, Microbiology, QR1-502
Abstract

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified by active surveillance (1/549, 0.18%), during the Delta wave (1/175, 0.57%). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. These cases demonstrate that, although uncommon in cats, a variety of clinical signs can occur.

Published
2023
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8. Increase in SARS-CoV-2 Seroprevalence in UK Domestic Felids Despite Weak Immunogenicity of Post-Omicron Variants

Author

Grace B. Tyson, Sarah Jones, Chloe Montreuil-Spencer, Nicola Logan, Sam Scott, Hagar Sasvari, Michael McDonald, Leigh Marshall, Pablo R. Murcia, Brian J. Willett, William Weir, and Margaret J. Hosie

Subjects
serology, SARS-CoV-2, coronaviruses, cats, feline infections, neutralising antibodies, Microbiology, QR1-502
Abstract

Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, the feline immune response to these variants is not well defined. We aimed to estimate the current seroprevalence of SARS-CoV-2 in UK pet cats, as well as characterise the neutralising antibody response to the Omicron (BA.1) variant. A neutralising seroprevalence of 4.4% and an overall seroprevalence of 13.9% was observed. Both purebred and male cats were found to have the highest levels of seroprevalence, as well as cats aged between two and five years. The Omicron variant was found to have a lower immunogenicity in cats than the B.1, Alpha and Delta variants, which reflects previous reports of immune and vaccine evasion in humans. These results further underline the importance of surveillance of SARS-CoV-2 infections in UK cats as the virus continues to evolve.

Published
2023
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9. mRNA or ChAd0x1 COVID-19 Vaccination of Adolescents Induces Robust Antibody and Cellular Responses With Continued Recognition of Omicron Following mRNA-1273

Author

Alexander C. Dowell, Annabel A. Powell, Chris Davis, Sam Scott, Nicola Logan, Brian J. Willett, Rachel Bruton, Morenike Ayodele, Elizabeth Jinks, Juliet Gunn, Eliska Spalkova, Panagiota Sylla, Samantha M. Nicol, Jianmin Zuo, Georgina Ireland, Ifeanyichukwu Okike, Frances Baawuah, Joanne Beckmann, Shazaad Ahmad, Joanna Garstang, Andrew J. Brent, Bernadette Brent, Marie White, Aedin Collins, Francesca Davis, Ming Lim, Jonathan Cohen, Julia Kenny, Ezra Linley, John Poh, Gayatri Amirthalingam, Kevin Brown, Mary E. Ramsay, Rafaq Azad, John Wright, Dagmar Waiblinger, Paul Moss, and Shamez N. Ladhani

Subjects
COVID-19, vaccine, paediatric, T-cell, antibody, neuro-disabilities, Immunologic diseases. Allergy, RC581-607
Abstract

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.

Published
2022
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10. Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination.

Author

Chris Davis, Nicola Logan, Grace Tyson, Richard Orton, William T Harvey, Jonathan S Perkins, Guy Mollett, Rachel M Blacow, COVID-19 Genomics UK (COG-UK) Consortium, Thomas P Peacock, Wendy S Barclay, Peter Cherepanov, Massimo Palmarini, Pablo R Murcia, Arvind H Patel, David L Robertson, John Haughney, Emma C Thomson, Brian J Willett, and COVID-19 DeplOyed VaccinE (DOVE) Cohort Study investigators

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Published
2021
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11. Correlating IgG Levels with Neutralising Antibody Levels to Indicate Clinical Protection in Healthcare Workers at Risk during a Measles Outbreak

Author

Siyuan Hu, Nicola Logan, Sarah Coleman, Cariad Evans, Brian J. Willett, and Margaret J. Hosie

Subjects
measles outbreak, healthcare workers, neutralising antibody, clinical protection, IgG testing, Microbiology, QR1-502
Abstract

The rapid transmission of measles poses a great challenge for measles elimination. Thus, rapid testing is required to screen the health status in the population during measles outbreaks. A pseudotype-based virus neutralisation assay was used to measure neutralising antibody titres in serum samples collected from healthcare workers in Sheffield during the measles outbreak in 2016. Vesicular stomatitis virus (VSV) pseudotypes bearing the haemagglutinin and fusion glycoproteins of measles virus (MeV) and carrying a luciferase marker gene were prepared; the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity. Spearman’s correlation coefficients between IgG titres and neutralising antibody levels ranged from 0.40 to 0.55 (p < 0.05) or from 0.71 to 0.79 (p < 0.0001) when the IgG titres were obtained using different testing kits. In addition, the currently used vaccine was observed to cross-neutralise most circulating MeV genotypes. However, the percentage of individuals being “well-protected” was lower than 95%, the target rate of vaccination coverage to eliminate measles. These results demonstrate that the level of clinical protection against measles in individuals could be inferred by IgG titre, as long as a precise correlation has been established between IgG testing and neutralisation assay; moreover, maintaining a high vaccination coverage rate is still necessary for measles elimination.

Published
2022
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12. Abstracts from the 3rd International Severe Asthma Forum (ISAF)

Author

M. E. Ketelaar, K. Van De Kant, F. N. Dijk, E. M. M. Klaassen, N. Grotenboer, M. C. Nawijn, E. Dompeling, G. H. Koppelman, Clare Murray, Philip Foden, Lesley Lowe, Hannah Durrington, Adnan Custovic, Angela Simpson, Andrew J. Simpson, Dominick E. Shaw, Ana R. Sousa, Louise J. Fleming, Graham Roberts, Ioannis Pandis, Aruna T. Bansal, Julie Corfield, Scott Wagers, Ratko Djukanovic, Kian Fan Chung, Peter J. Sterk, Jorgen Vestbo, Stephen J. Fowler, S. J. Tebbutt, A. Singh, C. P. Shannon, Y. W. Kim, C. X. Yang, G. M. Gauvreau, J. M. Fitzgerald, L. P. Boulet, P. M. O’Byrne, N. Begley, A. Loudon, D. W. Ray, Selene Baos, Lucía Cremades, David Calzada, Carlos Lahoz, Blanca Cárdaba, Kewal Asosingh, Chris Lauruschkat, Kimberly Queisser, Nicholas Wanner, Kelly Weiss, Weiling Xu, Serpil Erzurum, Milena Sokolowska, Li-Yuan Chen, Yueqin Liu, Asuncion Martinez-Anton, Carolea Logun, Sara Alsaaty, Rosemarie Cuento, Rongman Cai, Junfeng Sun, Oswald Quehenberger, Aaron Armando, Edward Dennis, Stewart Levine, James Shelhamer, Kilyong Choi, Snezhina Lazova, Penka Perenovska, Dimitrinka Miteva, Stamatios Priftis, Guergana Petrova, Vassil Yablanski, Evgeni Vlaev, Hristina Rafailova, Takashi Kumae, L. J. Holmes, J. Yorke, D. M. Ryan, Sasawan Chinratanapisit, Khlongtip Matchimmadamrong, Jitladda Deerojanawong, Wissaroot Karoonboonyanan, Paskorn Sritipsukho, Vania Youroukova, Denitsa Dimitrova, Yanina Slavova, Spaska Lesichkova, Iren Tzocheva, Snezhana Parina, Svetla Angelova, Neli Korsun, Mihai Craiu, Iustina Violeta Stan, Matea Deliu, Tolga Yavuz, Matthew Sperrin, Umit M. Sahiner, Danielle Belgrave, Cansin Sackesen Sackesen, Ömer Kalayci, Petar Velikov, Tsvetelina Velikova, Ekaterina Ivanova-Todorova, Kalina Tumangelova-Yuzeir, Dobroslav Kyurkchiev, Spyridon Megremis, Bede Constantinides, Alexandros Georgios Sotiropoulos, Paraskevi Xepapadaki, David Robertson, Nikolaos Papadopoulos, Maxim Wilkinson, Craig Portsmouth, David Ray, Royston Goodacre, Anna Valerieva, Irina Bobolea, Daiana Guillén Vera, Gabriel Gonzalez-Salazar, Carlos Melero Moreno, Consuelo Fernandez Rodriguez, Natividad De Las Cuevas Moreno, R. Wang, I. Satia, R. Niven, J. A. Smith, T. Southworth, J. Plumb, V. Gupta, J. Pearson, I. Ramis, M. D. Lehner, M. Miralpeix, D. Singh, Imran Satia, Mark Woodhead, Paul O’Byrne, Jaclyn Ann Smith, Cecilia Forss, Peter Cook, Sheila Brown, Freya Svedberg, Katherine Stephenson, Margherita Bertuzzi, Elaine Bignell, Malin Enerbäck, Danen Cunoosamy, Andrew Macdonald, Caini Liu, Liang Zhu, Kiochi Fukuda, Cunjin Zhang, Suidong Ouyang, Xing Chen, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li, Marie-Chantal Larose, Anne-Sophie Archambault, Véronique Provost, Jamila Chakir, Michel Laviolette, Nicolas Flamand, Nicola Logan, Dominik Ruckerl, Judith E. Allen, Tara E. Sutherland, E. Hamelmann, C. Vogelberg, S. Goldstein, G. E. Azzi, M. Engel, R. Sigmund, S. J. Szefler, Raquel Mesquita, Luis Coentrão, Rui Veiga, José-Artur Paiva, Roberto Roncon-Albuquerque, Wendy Vargas Porras, Ana González Moreno, Jesus Macías Iglesias, Gustavo Córdova Ramos, Yesenia Peña Acevedo, Miguel Angel Tejedor Alonso, Maria Del Mar Moro Moro, Irena Krcmova, Jakub Novosad, Nicola Alexander Hanania, Marc Massanari, Heike Hecker, Eric Kassel, Craig Laforce, Kathy Rickard, Sanne Snelder, Gert-Jan Braunstahl, T. L. Jones, D. Neville, E. R. Heiden, E. Lanning, T. Brown, H. Rupani, K. S. Babu, A. J. Chauhan, M. Y. Eldegeir, A. A. Chapman, M. Ferwana, and M. Caldron

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2017
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13. Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection.

Author

Tara E Sutherland, Dominik Rückerl, Nicola Logan, Sheelagh Duncan, Thomas A Wynn, and Judith E Allen

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Ym1 and RELMα are established effector molecules closely synonymous with Th2-type inflammation and associated pathology. Here, we show that whilst largely dependent on IL-4Rα signaling during a type 2 response, Ym1 and RELMα also have IL-4Rα-independent expression patterns in the lung. Notably, we found that Ym1 has opposing effects on type 2 immunity during nematode infection depending on whether it is expressed at the time of innate or adaptive responses. During the lung migratory stage of Nippostrongylus brasiliensis, Ym1 promoted the subsequent reparative type 2 response but once that response was established, IL-4Rα-dependent Ym1 was important for limiting the magnitude of type 2 cytokine production from both CD4+ T cells and innate lymphoid cells in the lung. Importantly, our study demonstrates that delivery of Ym1 to IL-4Rα deficient animals drives RELMα production and overcomes lung repair deficits in mice deficient in type 2 immunity. Together, Ym1 and RELMα, exhibit time and dose-dependent interactions that determines the outcome of lung repair during nematode infection.

Published
2018
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14. Myeloid cell recruitment versus local proliferation differentiates susceptibility from resistance to filarial infection

Author

Sharon M Campbell, Johanna A Knipper, Dominik Ruckerl, Conor M Finlay, Nicola Logan, Carlos M Minutti, Matthias Mack, Stephen J Jenkins, Matthew D Taylor, and Judith E Allen

Subjects
helminth, nematode, macrophages, type 2 immunity, Medicine, Science, Biology (General), QH301-705.5
Abstract

Both TH2-dependent helminth killing and suppression of the TH2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, Litomosoides sigmodontis. C57BL/6 mice exhibited a profoundly expanded resident MΦ (resMΦ) population, which was gradually replenished from the bone marrow in an age-dependent manner. Infection status did not alter the bone-marrow derived contribution to the resMΦ population, confirming local proliferation as the driver of resMΦ expansion. Significantly less resMΦ expansion was observed in the susceptible BALB/c strain, which instead exhibited an influx of monocytes that assumed an immunosuppressive PD-L2+ phenotype. Inhibition of monocyte recruitment enhanced nematode killing. Thus, the balance of monocytic vs. resident M(IL-4) numbers varies between inbred mouse strains and impacts infection outcome.

Published
2018
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15. Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies.

Author

Brian J Willett, Martin Kraase, Nicola Logan, Elizabeth McMonagle, Mariana Varela, and Margaret J Hosie

Subjects
Medicine, Science
Abstract

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development.

Published
2013
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16. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Author

Felicity Liew, Shubha Talwar, Andy Cross, Brian J. Willett, Sam Scott, Nicola Logan, Matthew K. Siggins, Dawid Swieboda, Jasmin K. Sidhu, Claudia Efstathiou, Shona C. Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A.A. Roger Thompson, Sarah L. Rowland-Jones, Annemarie B. Docherty, James D. Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G. Wootton, Susanna Dunachie, Jennifer K. Quint, Rachael A. Evans, Louise V. Wain, Sara Fontanella, Thushan I. de Silva, Antonia Ho, Ewen Harrison, J. Kenneth Baillie, Malcolm G. Semple, Christopher Brightling, Ryan S. Thwaites, Lance Turtle, Peter J.M. Openshaw, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian Griffin, Rishi K. Gupta, Ewen M. Harrison, Antonia Y.W. Ho, Karl Holden, Peter W. Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Matthew Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J. Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, Emma C. Thomson, Lance C.W. Turtle, Maria Zambon, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Lisa Norman, Riinu Pius, Catherine A. Shaw, Marie Connor, Jo Dalton, Carrol Gamble, Michelle Girvan, Sophie Halpin, Janet Harrison, Clare Jackson, James Lee, Laura Marsh, Daniel Plotkin, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Susan Knight, Eva Lahnsteiner, Gary Leeming, Lucy Norris, James Scott-Brown, Sarah Tait, Murray Wham, Richard Clark, Audrey Coutts, Lorna Donelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise MacGillivray, Alan Maclean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Gail Carson, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Tassos Grammatikopoulos, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Joanne Howard, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Thapas Nagarajan, Megan Nagel, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Sarah Sarah, Matthias Schmid, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Rachel Vincent, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, Sarah E. McDonald, Victoria Shaw, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Lisa Flaherty, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Hannah Massey, Nicole Maziere, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Seán Keating, Cara Donegan, Rebecca G. Spencer, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Wilna Oosthuyzen, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. Brunskill, M. Buch, P. Buckley, A. Bularga, E. Bullmore, L. Burden, T. Burdett, D. Burn, G. Burns, A. Burns, J. Busby, R. Butcher, A. 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Subjects
SARS-CoV-2 variants, Mucosal immunity, Nasal antibody, SDG 3 - Good Health and Well-being, Biochemistry, Genetics and Molecular Biology(all), SARS-CoV-2 immunity, Vaccination, COVID-19, General Medicine, Convalescent, General Biochemistry, Genetics and Molecular Biology
Abstract

Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.

Published
2022

17. Evaluation of the effect of maternally derived antibody on response to MMR vaccine in Thai infants

Author

Siyuan Hu, Nicola Logan, Jiratchaya Puenpa, Nasamon Wanlapakorn, Sompong Vongpunsawad, Yong Poovorawan, Brian J. Willett, and Margaret J. Hosie

Subjects
General Veterinary, General Immunology and Microbiology, Vaccination, Public Health, Environmental and Occupational Health, Infant, Antibodies, Viral, Thailand, Infectious Diseases, HEK293 Cells, Molecular Medicine, Humans, Mumps, Measles-Mumps-Rubella Vaccine, Rubella, Measles
Abstract

Background:\ud Although the number of measles cases declined globally in response to anti-measles immunisation campaigns, measles has re-emerged. A review of current vaccination policies is required to improve measles elimination strategies.\ud \ud Methods:\ud A pseudotype-based virus neutralisation assay (PVNA) was used to measure neutralising antibody titres in serum samples collected from Thai infants at six timepoints before and after two-doses of MMR (1 & 2) vaccination (ClinicalTrials.gov no. NCT02408926). Vesicular stomatitis virus (VSV) luciferase pseudotypes bearing the haemaglutinin (H) and fusion (F) glycoproteins of measles virus (MeV) were prepared. Serial dilutions of serum samples were incubated with VSV (MeV) pseudotypes and plated onto HEK293-human SLAM1 cells; the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity.\ud \ud Results:\ud Neutralising antibody titres in infants born with high levels of maternal immunity (H group) persisted at the time of the first MMR vaccination, and those infants did not respond effectively by developing protective titres. In contrast, infants with lower maternal immunity (L group) developed protective titres of antibody following vaccination. Responses to the second MMR vaccination were significantly higher (P = 0.0171, Wilcoxon signed-rank test) in the H group. The observed correlation between anti-MeV IgG level and neutralising antibody titre in Thai infants indicates the possibility of using rapid IgG testing as a surrogate measure for neutralising activity to define clinical protection levels within populations.\ud \ud Conclusion:\ud These results demonstrate that varying the timing of the first MMR immunisation according to the level of acquired maternal immunity could increase vaccination immunogenicity and hence accelerate measles eradication.

Published
2022

18. Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver

Author

Lucy H. Jackson-Jones, Dietmar M. W. Zaiss, Emma Ringqvist, Raquel Guillamat-Prats, Tara E. Sutherland, Antonio Artigas, Zissis C. Chroneos, Belén García-Fojeda, Cordula Stamme, Nicola Logan, Johanna A. Knipper, Judith E. Allen, Carlos M. Minutti, Cristina Casals, and David A. Ferenbach

Subjects
0301 basic medicine, Multidisciplinary, Biology, medicine.disease, Surfactant protein A, Type 2 immune response, 03 medical and health sciences, Peritoneal cavity, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Immune system, Fibrosis, Immunology, medicine, Macrophage, Macrophage proliferation, Tissue homeostasis, 030215 immunology
Abstract

Local macrophage clean-up Infection, especially by helminths or bacteria, can cause tissue damage (see the Perspective by Bouchery and Harris). Minutti et al. studied mouse models of helminth infection and fibrosis. They expressed surfactant protein A (a member of the complement component C1q family) in the lung, which enhanced interleukin-4 (IL-4)-mediated proliferation and activation of alveolar macrophages. This activation accelerated helminth clearance and reduced lung injury. In the peritoneum, C1q boosted macrophage activation for liver repair after bacterial infection. By a different approach, Bosurgi et al. discovered that after wounding caused by migrating helminths in the lung or during inflammation in the gut of mice, IL-4 and IL-13 act only in the presence of apoptotic cells to promote tissue repair by local macrophages. Science , this issue p. 1076 , p. 1072 ; see also p. 1014

Published
2017

19. Abstracts from the 3rd International Severe Asthma Forum (ISAF)

Author

Khlongtip Matchimmadamrong, J. Yorke, M. C. Nawijn, David Robertson, Serpil C. Erzurum, Evgeni Vlaev, Matthew Sperrin, Cecilia Forss, Jun Qin, A. A. Chapman, E. M. M. Klaassen, K. S. Babu, Tsvetelina Velikova, Consuelo Fernandez Rodriguez, Natividad De Las Cuevas Moreno, Rui Veiga, Nicola Logan, Clare S. Murray, Dominick E. Shaw, Vandana Gupta, Peter C. Cook, Li-Yuan Chen, Junfeng Sun, Louise Fleming, Sanne M. Snelder, Irina Bobolea, Dave Singh, N. Begley, James Shelhamer, Xing Chen, Kimberly Queisser, Gabriel Gonzalez-Salazar, Dan Neville, Freya Svedberg, Andrew Simpson, Jamila Chakir, C. P. Shannon, L. J. Holmes, Mark Woodhead, Philip Foden, Maria Del Mar Moro Moro, Yueqin Liu, Judith E. Allen, Gail M. Gauvreau, Paskorn Sritipsukho, Gustavo Córdova Ramos, Caini Liu, Miguel Angel Tejedor Alonso, Liang Zhu, Peter J. Sterk, Xiaoxia Li, David W. Ray, Stan Szefler, E. Dompeling, Blanca Cárdaba, Edward Dennis, Daiana Guillén Vera, Rosemarie Cuento, Oswald Quehenberger, Ana González Moreno, Kathy Rickard, Ellie Lanning, Kalina Tumangelova-Yuzeir, Eckard Hamelmann, Bede Constantinides, Tom C. Brown, M. Caldron, G. E. Azzi, Marie-Chantal Larose, Carlos Lahoz, Luis Coentrão, Andrew Macdonald, Penka Perenovska, Michael Engel, F. N. Dijk, Yesenia Peña Acevedo, S. J. Tebbutt, M. E. Ketelaar, I. Satia, Weiling Xu, Nicolas Flamand, Isabel Ramis, José-Artur Paiva, Maxim Wilkinson, Martin D. Lehner, J. M. Fitzgerald, Eric Kassel, Nicholas Wanner, Takashi Kumae, Y. W. Kim, N. Grotenboer, S. Goldstein, Montserrat Miralpeix, Kian Fan Chung, Omer Kalayci, Véronique Provost, Umit Murat Sahiner, Anne-Sophie Archambault, M. Ferwana, Milena Sokolowska, M. Y. Eldegeir, Svetla Angelova, Sasawan Chinratanapisit, David Calzada, Kilyong Choi, Nikolaos G. Papadopoulos, Matea Deliu, Spaska Lesichkova, Roberto Roncon-Albuquerque, Ana R. Sousa, Scott Wagers, Tolga S Yavuz, Vassil Yablanski, Margherita Bertuzzi, D. M. Ryan, Carlos Melero Moreno, Carolea Logun, Christian Vogelberg, Elaine Bignell, Petar Velikov, Ratko Djukanovic, Ralf Sigmund, Anna Valerieva, Spyridon Megremis, Snezhina Lazova, R. Niven, A. Singh, Danen Cunoosamy, Paraskevi Xepapadaki, Craig Laforce, Wendy Vargas Porras, Aruna T. Bansal, Adnan Custovic, Michel Laviolette, Chris Lauruschkat, Jakub Novosad, Katherine Stephenson, Jesus Macías Iglesias, Paul M. O'Byrne, R. Wang, Yanina Slavova, K.D.G. van de Kant, Cunjin Zhang, Ekaterina Ivanova-Todorova, Wissaroot Karoonboonyanan, Iren Tzocheva, Tara E. Sutherland, Jørgen Vestbo, Selene Baos, Mihai Craiu, Andrew S. I. Loudon, Guergana Petrova, Aaron Armando, Danielle Belgrave, Dimitrinka Miteva, Suguna Rachakonda, Lucía Cremades, Craig Portsmouth, Royston Goodacre, Marc Massanari, Sheila Brown, C. X. Yang, Irena Krčmová, Louis P. Boulet, Suidong Ouyang, Snezhana Parina, Thomas Southworth, Vania Youroukova, Sara Alsaaty, Anoop Chauhan, P. M. O’Byrne, Emily Heiden, Mark A. Aronica, Hristina Rafailova, J. Pearson, Kelly Weiss, J. A. Smith, Imran Satia, Angela Simpson, Dominik Rückerl, Dobroslav Kyurkchiev, Jitladda Deerojanawong, Asuncion Martinez-Anton, Kiochi Fukuda, Graham Roberts, Neli Korsun, Jaclyn A. Smith, Kewal Asosingh, Lesley Lowe, Gerard H. Koppelman, Nicola A. Hanania, Stewart Levine, Raquel Mesquita, Denitsa Dimitrova, Stamatios Priftis, Heike Hecker, Hannah J. Durrington, Ioannis Pandis, Julie Corfield, Hitasha Rupani, D. W. Ray, Iustina Violeta Stan, Thomas Jones, Gert-Jan Braunstahl, Alexandros Georgios Sotiropoulos, Rongman Cai, Luke Qin, Stephen J. Fowler, Malin Enerbäck, Jonathan Plumb, Cansin Sackesen, and Çocuk Sağlığı ve Hastalıkları

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Allergy, business.industry, Severe asthma, Immunology, RC581-607, medicine.disease, Meeting Abstracts, medicine, Immunology and Allergy, Immunologic diseases. Allergy, Intensive care medicine, business
Published
2017
Full Text
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20. COPD guidelines.

Author

Nicola Logan

Subjects
*NURSES, *CAREER development, *OBSTRUCTIVE lung diseases, *LUNG diseases, *RESEARCH
Abstract

Recounts the experience of British nurse Nicola Logan of improving her knowledge of chronic obstructive pulmonary disease after reading a continuing professional development article. Background on the article that examined the National Institute for Health and Clinical Excellence's guide identifying key priorities likely to have the greatest impact on patients and the National Health Service; Thoroughness of the article; Information provided.

Published
2005

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