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in category allergy and immunology

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1: Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
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Posted 01 Feb 2021

Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
110,611 downloads medRxiv allergy and immunology

Florian Krammer, Komal Srivastava, PARIS team, Viviana Simon

As COVID-19 vaccines are getting rolled out, an important question is arising: Should individuals who already had a SARS-CoV-2 infection receive one or two shots of the currently authorized mRNA vaccines. In this short report, we are providing evidence that the antibody response to the first vaccine dose in individuals with pre-existing immunity is equal to or even exceeds the titers found in naive individuals after the second dose. We also show that the reactogenicity is significantly higher in individuals who already have been infected with SARS-CoV-2 in the past. Changing the policy to give these individuals only one dose of vaccine would not negatively impact on their antibody titers, spare them from unnecessary pain and free up many urgently needed vaccine doses.

2: A serological assay to detect SARS-CoV-2 seroconversion in humans
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Posted 18 Mar 2020

A serological assay to detect SARS-CoV-2 seroconversion in humans
97,825 downloads medRxiv allergy and immunology

Fatima Amanat, Daniel Stadlbauer, Shirin Strohmeier, Thi HO Nguyen, Veronika Chromikova, Meagan McMahon, Kaijun Jiang, Guha Asthagiri Arunkumar, Denise Jurczyszak, Jose Polanco, Maria Bermudez-Gonzalez, Giulio Kleiner, Teresa Aydillo, Lisa Miorin, Daniel Fierer, Luz Amarilis Lugo, Erna Milunka Kojic, Jonathan Stoever, Sean T.H. Liu, Charlotte Cunningham-Rundles, Philip L Felgner, Thomas Moran, Adolfo Garcia-Sastre, Daniel Caplivski, Allen Cheng, Katherine Kedzierska, Olli Vapalahti, Jussi Hepojoki, Viviana Simon, Florian Krammer

IntroductionSARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. MethodsHere we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. These assays were developed with negative control samples representing pre-COVID 19 background immunity in the general population and samples from COVID19 patients. ResultsThe assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as 3 days post symptom onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. ConclusionSerological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of Coronavirus SARS-Cov-2 antibody titers will also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.

3: Evidence for Aerosol Transfer of SARS-CoV2-specific Humoral Immunity
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Posted 01 May 2022

Evidence for Aerosol Transfer of SARS-CoV2-specific Humoral Immunity
39,289 downloads medRxiv allergy and immunology

Ross Kedl, Elena Hsieh, Thomas E Morrison, Gabriela Samayoa-Reyes, Siobhan Flaherty, Conner Jackson, Rosemary Rochford

Abstract. Despite the obvious knowledge that infectious particles can be shared through respiration, whether other constituents of the nasal/oral fluids can be passed between hosts has surprisingly never even been postulated, let alone investigated. The circumstances of the present pandemic facilitated a unique opportunity to fully examine this provocative idea. The data we show provides evidence for a new mechanism by which herd immunity may be manifested, the aerosol transfer of antibodies between immune and non- immune hosts.

4: The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing
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Posted 26 Feb 2020

The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing
28,647 downloads medRxiv allergy and immunology

Minfeng Liao, Yang Liu, Jin Yuan, Yanling Wen, Gang Xu, Juanjuan Zhao, Lin Chen, Jinxiu Li, Xin Wang, Fuxiang Wang, Lei Liu, Shuye Zhang, Zheng Zhang

The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19. HighlightsO_LIImmune microenvironment of SARS-CoV-2-infected lungs revealed by scRNA/TCR seq C_LIO_LIIncreased inflammatory FCN1+ macrophages are replacing FABP4+ macrophages in the BALF from severe COVID-19 patients C_LIO_LIHighly expanded and functional competent tissue resident clonal CD8+ T cells in mild COVID-19 patients C_LI

5: Obesity may hamper SARS-CoV-2 vaccine immunogenicity
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Posted 26 Feb 2021

Obesity may hamper SARS-CoV-2 vaccine immunogenicity
21,798 downloads medRxiv allergy and immunology

Raul Pellini, Aldo Venuti, Fulvia Pimpinelli, Elva Abril, Giovanni Blandino, Flaminia Campo, Laura Conti, Armando De Virgilio, Federico De Marco, Enea Gino Di Domenico, Ornella Di Bella, Simona Di Martino, Fabrizio Ensoli, Diana Giannarelli, Chiara Mandoj, Valentina Manciocco, Paolo Marchesi, Francesco Mazzola, Silvia Moretto, Gerardo Petruzzi, Fabrizio Petrone, Barbara Pichi, Martina Pontone, Jacopo Zocchi, Antonello Vidiri, Branka Vujovic, Giulia Piaggio, Aldo Morrone, Gennaro Ciliberto

BackgroundThe first goal of the study was to analyse the antibody titre 7 days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and BMI. MethodsParticipants were assigned to receive the priming dose at baseline and booster dose at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Findings248 HWCs were analysed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7); was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. The antibody titre was found to be higher in young and female participants. A strong correlation of BMI classes with antibody titres was noticed: humoral response was more efficient in the group with under- and normal-weight vs the group with pre- and obesity participants (p<0.0001 at T1). InterpretationThese findings imply that females, lean and young people have an increased capacity to mount humoral immune responses compared to males, overweight and the older population. Although further studies are needed, this data may have important implications for the development of vaccination strategies for COVID-19, particularly in obese people. FundingNone

6: Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 infection
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Posted 01 Jul 2021

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 infection
15,719 downloads medRxiv allergy and immunology

Leo Swadling, Mariana O. Diniz, Nathalie M. Schmidt, Oliver E Amin, Aneesh Chandran, Emily Shaw, Corinna Pade, Joseph M Gibbons, Nina Le Bert, Anthony T Tan, Christine Y. L. Tham, Cedric Tan, Stephanie Kucyowicz, Gloryanne Aidoo-Micah, Joshua Rosenheim, Jessica Davies, Melanie P. Jensen, George Joy, Laura E McCoy, Ana M Valdes, Lucy van Dorp, Daniel M. Altmann, Rosemary J. Boyton, Charlotte Manisty, Thomas A Treibel, James C Moon, COVIDsortium Investigators, Francois Balloux, Aine McKnight, Mahdad Noursadeghi, Antonio Bertoletti, Mala Maini

Individuals with likely exposure to the highly infectious SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1-5. We hypothesised that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-26-12, would expand in vivo to mediate rapid viral control, potentially aborting infection. We studied T cells against the replication transcription complex (RTC) of SARS-CoV-2 since this is transcribed first in the viral life cycle13-15 and should be highly conserved. We measured SARS-CoV-2-reactive T cells in a cohort of intensively monitored healthcare workers (HCW) who remained repeatedly negative by PCR, antibody binding, and neutralisation for SARS-CoV-2 (exposed seronegative, ES). 16-weeks post-recruitment, ES had memory T cells that were stronger and more multispecific than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). The postulate that HCW with the strongest RTC-specific T cells had an abortive infection was supported by a low-level increase in IFI27 transcript, a robust early innate signature of SARS-CoV-2 infection16. We showed that the RNA-polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and was preferentially targeted by T cells from UK and Singapore pre-pandemic cohorts and from ES. RTC epitope-specific T cells capable of cross-recognising HCoV variants were identified in ES. Longitudinal samples from ES and an additional validation cohort, showed pre-existing RNA-polymerase-specific T cells expanded in vivo following SARS-CoV-2 exposure, becoming enriched in the memory response of those with abortive compared to overt infection. In summary, we provide evidence of abortive seronegative SARS-CoV-2 infection with expansion of cross-reactive RTC-specific T cells, highlighting these highly conserved proteins as targets for future vaccines against endemic and emerging Coronaviridae.

7: Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
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Posted 27 Apr 2021

Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
12,502 downloads medRxiv allergy and immunology

Kristen W Cohen, Susanne L. Linderman, Zoe Moodie, Julie Czartoski, Lilin Lai, Grace Mantus, Carson Norwood, Lindsay E. Nyhoff, Venkata-Viswanadh Edara, Katharine Floyd, Stephen C DeRosa, Hasan Ahmed, Rachael Whaley, Shivan N. Patel, Brittany Prigmore, Maria P Lemos, Carl W Davis, Sarah Furth, James O'Keefe, Mohini P. Gharpure, Sivaram Gunisetty, Kathy A. Stephens, Rustom Antia, Veronika I Zarnitsyna, David S Stephens, Srilatha Edupuganti, Nadine Rouphael, Evan J. Anderson, Aneesh K. Mehta, Jens Wrammert, Mehul S. Suthar, Rafi Ahmed, M. Juliana McElrath

Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. We evaluated 254 COVID-19 patients longitudinally from early infection and for eight months thereafter and found a predominant broad-based immune memory response. SARS-CoV-2 spike binding and neutralizing antibodies exhibited a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. In addition, there was a sustained IgG+ memory B cell response, which bodes well for a rapid antibody response upon virus re-exposure. Polyfunctional virus-specific CD4+ and CD8+ T cells were also generated and maintained with an estimated half-life of 200 days. Interestingly, the CD4+ T cell response equally targeted several SARS-CoV-2 proteins, whereas the CD8+ T cell response preferentially targeted the nucleoprotein, highlighting the importance of including the nucleoprotein as a potential vaccine antigen. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.

8: Antibody and T cell responses to Sinopharm/BBIBP-CorV in naive and previously infected individuals in Sri Lanka
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Posted 19 Jul 2021

Antibody and T cell responses to Sinopharm/BBIBP-CorV in naive and previously infected individuals in Sri Lanka
11,713 downloads medRxiv allergy and immunology

Chandima Jeewandara, Inoka Sepali Aberathna, Pradeep Dharshana Pushpakumara, Achala Kamaladasa, Dinuka Guruge, Deshni Jayathilaka, Banuri Gunesekara, Shyrar Tanussiya, Heshan Kuruppu, Thushali Ranasinghe, Shashika Dayarathne, Osanda Dissanayaka, Nayanathara Gamalath, Dinithi Ekanayaka, M.P.D.J. Jayamali, Ayesha Wijesinghe, Madushika Dissanayaka, Deshan Madushanka, Tibutius Jayadas, Anushika Mudunkotuwa, Gayasha Somathilaka, Michael James Harvie, Thashmi Nimasha, Saubhagya Danasekara, Ruwan Wijayamuni, Lisa Schimanski, Tiong Tan, Tao Dong, Alain R Townsend, Graham Ogg, Gathsaurie Neelika Malavige

Background: As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. Methods: SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor binding domain (RBD) of the wild type (WT), B.1.1.7, B.1.351 and B.1.617.2, ex vivo and cultured IFN{gamma} ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 weeks and at 6 weeks (2 weeks after the second dose). Results: 95% of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p<0.001) in individuals >60 years (93.3%) compared to those who were 20 to 39 years (98.9%). 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p=0.44). Vaccinees had significantly less (p<0.0001) antibodies to the RBD of WT and B.1.1.7, although there was no difference in antibodies to the RBD of B.1.351 and B.1.617.2 compared to convalescent sera. 27.7% of 46.4% of vaccinees had ex vivo IFN{gamma} and cultured ELISpot responses respectively, and IFN{gamma} and CD107a responses were detected by flow cytometry. Conclusions: Sinopharm/BBIBP-CorV appeared to induce high seroconversion rates and induce a similar level of antibody responses against ACE2 receptor, B.1.617.2 and B.1.351 as seen following natural infection.

9: Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults
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Posted 21 Sep 2021

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults
11,517 downloads medRxiv allergy and immunology

Ritthideach Yorsaeng, Nungruthai Suntronwong, Harit Phowatthanasathian, Suvichada Assawakosri, Sitthichai Kanokudom, Thanunrat Thongmee, Preeyaporn Vichaiwattana, Chompoonut Auphimai, Lakkhana Wongsrisang, Donchida Srimuan, Thaksaporn Thatsanatorn, Sirapa Klinfueng, Natthinee Sudhinaraset, Nasamon Wanlapakorn, Yong Poovorawan

In June 2021, Thailand was hit by the delta variant of SARS-CoV-2 resulting in the biggest wave of COVID-19. Due to the widespread delta variant, more than 600 healthcare workers had COVID-19 despite completion of two-dose CoronaVac. The Ministry of Public Health recommended that healthcare workers received a third dose of AZD1222 to increase level of protection against SARS-CoV-2. However, immune response after the third vaccination with AZD1222 are limited. In this study, sera from those who received a booster of AZD1222 in June-July 2021 were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG, anti-RBD total immunoglobulins and anti-spike protein 1 (S1) IgA. The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern (B.1.1.7, B.1.617.2, and B.1.351) using an enzyme-linked immunosorbent assay-based surrogate virus neutralization test. Participants who received the booster of AZD1222 possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than that two-dose vaccines (p < 0.001). They also elicited higher neutralizing activity against the wild type and all variants of concern than those in the recipients of the two-dose vaccines. This study demonstrated a high immunogenicity of the AZD1222 booster who completed the two-dose inactivated vaccines.

10: Pre-existing T cell memory as a risk factor for severe 1 COVID-19 in the elderly
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Posted 18 Sep 2020

Pre-existing T cell memory as a risk factor for severe 1 COVID-19 in the elderly
10,444 downloads medRxiv allergy and immunology

Petra Bacher, Elisa Rosati, Daniela Esser, Gabriela Rios Martini, Carina Saggau, Esther Schiminsky, Justina Dargvainiene, Ina Schr&amp;oumlder, Imke Wieters, Fabian Eberhardt, Holger Neb, Yascha Khodamoradi, Michael Sonntagbauer, Maria J.G.T. Vehreschild, Claudio Conrad, Florian Tran, Philip Rosenstiel, Robert Markewitz, Klaus-Peter Wandinger, Jan Rybniker, Matthias Kochanek, Frank Leypoldt, Oliver Andreas Cornely, Philipp Koehler, Andre Franke, Alexander Scheffold

Coronavirus disease 2019 (COVID-19) displays high clinical variability but the parameters that determine disease severity are still unclear. Pre-existing T cell memory has been hypothesized as a protective mechanism but conclusive evidence is lacking. Here we demonstrate that all unexposed individuals harbor SARS-CoV-2-specific memory T cells with marginal cross-reactivity to common cold corona and other unrelated viruses. They display low functional avidity and broad protein target specificities and their frequencies correlate with the overall size of the CD4+ memory compartment reflecting the immunological age of an individual. COVID-19 patients have strongly increased SARS-CoV-2-specific inflammatory T cell responses that are correlated with severity. Strikingly however, patients with severe COVID-19 displayed lower TCR functional avidity and less clonal expansion. Our data suggest that a low avidity pre-existing T cell memory negatively impacts on the T cell response quality against neoantigens such as SARS-CoV-2, which may predispose to develop inappropriate immune reactions especially in the elderly. We propose the immunological age as an independent risk factor to develop severe COVID-19.

11: Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2
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Posted 20 Mar 2020

Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2
9,332 downloads medRxiv allergy and immunology

Ling Ni, Fang Ye, Meng-Li Chen, Yu Feng, Yong-Qiang Deng, Hui Zhao, Peng Wei, Jiwan Ge, Xiaoli Li, Lin Sun, Pengzhi Wang, Peng Liang, Han Guo, Xinquan Wang, Cheng-Feng Qin, Fang Chen, Chen Dong

The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.

12: Heterologous vaccination with inactivated and mRNA vaccines increases B and T cell responses to SARS-CoV-2
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Posted 05 Jan 2022

Heterologous vaccination with inactivated and mRNA vaccines increases B and T cell responses to SARS-CoV-2
9,332 downloads medRxiv allergy and immunology

Fanglei Zuo, Hassan Abolhassani, Likun Du, Antonio Piralla, Federico Bertoglio, Leire de Campos-Mata, Hui Wan, Maren Schubert, Yating Wang, Rui Sun, Irene Cassaniti, Stelios Vlachiotis, Makiko Kumagai-Braesch, Juni Andrell, Zhaoxia Zhang, Yintong Xue, Esther Veronika Wenzel, Luigi Calzolai, Luca Varani, Nima Rezaei, Zahra Chavoshzadeh, Fausto Baldanti, Michael Hust, Lennart Hammarstrom, Harold Marcotte, Qiang Pan-Hammarstrom

Abstract Background There has been an unprecedented global effort to produce safe and effective vaccines against SARS-CoV-2. However, production challenges, supply shortages and unequal global reach, together with an increased number of breakthrough infections due to waning of immunity and the emergence of new variants of concern (VOC), have prolonged the pandemic. To boost the immune response, several heterologous vaccination regimes have been tested and have shown increased antibody responses compared to homologous vaccination. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines. Methods The levels of specific antibodies against the receptor-binding domain (RBD) of the spike protein from wild-type virus and the Beta, Delta and Omicron variants were measured in healthy individuals who had received two doses of homologous inactivated (BBIBP-CorV or CoronoVac) or mRNA (BNT162b2 or mRNA-1273) vaccines, and in donors who were given an mRNA vaccine boost after two doses of either vaccine. Pre-vaccinated healthy donors, or individuals who had been infected and subsequently received the mRNA vaccine were also included as controls. In addition, specific memory B and T cell responses were measured in a subset of samples. Results A booster dose of an mRNA vaccine significantly increased the specific antibody response to the wild-type and VOCs including Omicron (by 14-fold), in individuals who had previously received two doses of inactivated vaccines. The levels of specific antibodies in the heterologous vaccination group were similar to those in individuals receiving a third dose of homologous mRNA vaccines or boosted with mRNA vaccine after natural infection. Furthermore, this heterologous vaccination regime significantly improved the specific memory B and T cell responses. Conclusions Heterologous prime-boost immunization with inactivated vaccine followed by an mRNA vaccine boost markedly increased the levels of specific antibodies and B and T cell responses and may thus increase protection against emerging SARS-CoV-2 variants including Omicron.

13: Antibody Response after Second-dose of ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) among Health Care Workers in India: Final Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study
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Posted 04 Jun 2021

Antibody Response after Second-dose of ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) among Health Care Workers in India: Final Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study
9,319 downloads medRxiv allergy and immunology

AWADHESH KUMAR SINGH, Sanjeev Ratnakar Phatak, RITU SINGH, Kingshuk Bhattacharjee, Nagendra Kumar Singh, Arvind Gupta, Arvind Sharma

Background: We assessed the humoral immune response after the completion of two doses of both ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) vaccines in Indian health care workers (HCW). Methods: A Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study was conducted that measured SARS-CoV-2 anti-spike binding antibody quantitatively, 21 days or more after the first and second dose of two vaccines in both severe acute respiratory syndrome (SARS-CoV-2) naive and recovered HCW. Primary aim was to analyze antibody response (seropositivity rate and median [inter-quartile range, IQR] antibody titre) following each dose of both vaccines and its correlation to age, sex, blood group, body mass index (BMI) and comorbidities. Here we report the final results of anti-spike antibody response after the two completed doses. Results: Among the 515 HCW (305 Male, 210 Female), 95.0% showed seropositivity after two doses of both vaccines. Of the 425 Covishield and 90 Covaxin recipients, 98.1% and 80.0% respectively, showed seropositivity. However, both seropositivity rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient (98.1 vs. 80.0%; 127.0 vs. 53 AU/mL; both p<0.001). This difference persisted in 457 SARS-CoV-2 naive cohorts and propensity-matched (age, sex and BMI) analysis of 116 cohorts. While no difference was observed in relation to sex, BMI, blood group and any comorbidities; people with age >60 years or those with type 2 diabetes had a significantly lower seropositivity rates. Both vaccine recipients had similar solicited mild to moderate adverse events and none had severe or unsolicited side effects. In SARS-CoV-2 naive cohorts, sex, presence of comorbidities, and vaccine type were independent predictors of antibody positivity rate in multiple logistic regression analysis. Conclusions: Both vaccines elicited good immune response after two doses, although seropositivity rates and median anti-spike antibody titre was significantly higher in Covishield compared to Covaxin arm.

14: SARS-CoV-2 seroconversion in health care workers
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Posted 19 May 2020

SARS-CoV-2 seroconversion in health care workers
8,908 downloads medRxiv allergy and immunology

Adrian Shields, Sian E Faustini, Marisol Perez-Toledo, Sian Jossi, Erin L Aldera, Joel D Allen, Saly Al-Taei, Claire Backhouse, Andrew Bosworth, Lyndsey Dunbar, Daniel Ebanks, Beena Emmanuel, Joanne Grey, I Michael Kidd, Golaeh McGinnell, Dee McLoughlin, Gabriella Morley, Joanne O'Neill, Danai Papakonstantinou, Oliver Pickles, Charlotte Poxon, Megan Richter, Eloise Walker, Kasun Wanigasooriya, Yasunori Watanabe, Celina Whalley, Agnieszka E Zielinska, Max Crispin, David C Wraith, Andrew D Beggs, Adam F Cunningham, Mark T Drayson, Alex G Richter

Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, {chi}2 =21.1034, p<0.0001). In the week preceding peak COVID-19-related mortality at UHBFT, seroconversion rates amongst those who were suffering from symptomatic illnesses peaked at 77.8%. Prior symptomatic illness generated quantitatively higher antibody responses than asymptomatic seroconversion. Seroconversion rates were highest amongst those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%) with lower rates observed in participants working in intensive care (14.8%) and emergency medicine (13.3%). Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices.

15: Safety, Immunogenicity, and Efficacy of a COVID-19 Vaccine (NVX-CoV2373) Co-administered With Seasonal Influenza Vaccines
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Posted 13 Jun 2021

Safety, Immunogenicity, and Efficacy of a COVID-19 Vaccine (NVX-CoV2373) Co-administered With Seasonal Influenza Vaccines
8,076 downloads medRxiv allergy and immunology

Paul Heath, Seth Toback, Eva Galiza, Catherine Cosgrove, James B Galloway, Anna L. Goodman, Pauline A. Swift, Sankarasubramanian Rajaram, Alison Graves-Jones, Jonathan Edelman, Fiona Burns, Angela M. Minassian, Iksung Cho, Lakshmi Kumar, Joyce S. Plested, E. Joy Rivers, Andreana Robertson, Filip Dubovsky, Greg Glenn

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines has not yet been reported. Methods A sub-study on influenza vaccine co-administration was conducted as part of the phase 3 randomized trial of the safety and efficacy of NVX-CoV2373. The first ~400 participants meeting main study entry criteria and with no contraindications to influenza vaccination were invited to join the sub-study. After randomization in a 1:1 ratio to receive NVX-CoV2373 (n=217) or placebo (n=214), sub-study participants received an age-appropriate, licensed, open-label influenza vaccine with dose 1 of NVX-CoV2373. Reactogenicity was evaluated via electronic diary for 7 days post-vaccination in addition to monitoring for unsolicited adverse events (AEs), medically-attended AEs (MAAEs), and serious AEs (SAEs). Influenza haemagglutination inhibition and SARS-CoV-2 anti-spike IgG assays were performed. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed. Comparisons were made between sub-study and main study participants. Findings Sub-study participants were younger, more racially diverse, and had fewer comorbid conditions than main study participants. Reactogenicity events more common in the co-administration group included tenderness (70.1% vs 57.6%) or pain (39.7% vs 29.3%) at injection site, fatigue (27.7% vs 19.4%), and muscle pain (28.3% vs 21.4%). Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. Co-administration resulted in no change to influenza vaccine immune response, while a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. Vaccine efficacy in the sub-study was 87.5% (95% CI: -0.2, 98.4) while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5). Interpretation This is the first study to demonstrate the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. The results suggest concomitant vaccination may be a viable immunisation strategy. Funding This study was funded by Novavax, Inc.

16: Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination
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Posted 05 Apr 2021

Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination
7,684 downloads medRxiv allergy and immunology

Lucie Loyal, Julian Braun, Larissa Henze, Beate Kruse, Manuela Dingeldey, Ulf Reimer, Florian Kern, Tatjana Schwarz, Maike Mangold, Clara Unger, Friederike Doerfler, Shirin Kadler, Jennifer Rosowski, Kuebrah Guercan, Zehra Uyar-Aydin, Marco Frentsch, Florian Kurth, Karsten Schnatbaum, Maren Eckey, Stefan Hippenstiel, Andreas C. Hocke, Marcel A Mueller, Birgit Sawitzki, Stefan Miltenyi, Friedemann Paul, Marcus A. Mall, Holger Wenschuh, Sebastian Voigt, Christian Drosten, Roland Lauster, Nils Lachmann, Leif-Erik Sander, Victor Max Corman, Jobst Roehmel, Lil Antonia Meyer-Arndt, Andreas M Thiel, Claudia Giesecke-Thiel

While evidence for pre-existing SARS-CoV-2-cross-reactive CD4+ T cells in unexposed individuals is increasing, their functional significance remains unclear. Here, we comprehensively determined SARS-CoV-2-cross-reactivity and human coronavirus-reactivity in unexposed individuals. SARS-CoV-2-cross-reactive CD4+ T cells were ubiquitous, but their presence decreased with age. Within the spike glycoprotein fusion domain, we identified a universal immunodominant coronavirus-specific peptide epitope (iCope). Pre-existing spike- and iCope-reactive memory T cells were efficiently recruited into mild SARS-CoV-2 infections and their abundance correlated with higher IgG titers. Importantly, the cells were also reactivated after primary BNT162b2 COVID-19 mRNA vaccination in which their kinetics resembled that of secondary immune responses. Our results highlight the functional importance of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Abundant spike-specific cross-immunity may be responsible for the unexpectedly high efficacy of current vaccines even with single doses and the high rate of asymptomatic/mild infection courses.

17: Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine.
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Posted 02 Mar 2022

Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine.
7,568 downloads medRxiv allergy and immunology

Sitthichai Kanokudom, Suvichada Assawakosri, Nungruthai Suntronwong, Jira Chansaenroj, Chompoonut Auphimai, Pornjarim Nilyanimit, Preeyaporn Vichaiwattana, Thanunrat Thongmee, Ritthideach Yorsaeng, Thaneeya Duangchinda, Warangkana Chantima, Pattarakul Pakchotanon, Donchida Srimuan, Thaksaporn Thatsanatorn, Sirapa Klinfueng, Juthathip Mongkolsapaya, Natthinee Sudhinaraset, Nasamon Wanlapakorn, Sittisak Honsawek, Yong Poovorawan

The coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 g- than the 30 g-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 g- than the 50 g-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply.

18: ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism
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Posted 07 Feb 2020

ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism
7,434 downloads medRxiv allergy and immunology

Jun Wang, Shanmeizi Zhao, Ming Liu, Zhiyao Zhao, Yiping Xu, Ping Wang, Meng Lin, Yanhui Xu, Bing Huang, Xiaoyu Zuo, Zhanghua Chen, Fan Bai, Jun Cui, Andrew M Lew, Jincun Zhao, Yan Dora Zhang, Hai-Bin Luo, Yuxia Zhang

Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection.

19: In vitro Characterization of SARS-CoV-2 Protein Translated from the Moderna mRNA-1273 Vaccine
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Posted 02 Mar 2022

In vitro Characterization of SARS-CoV-2 Protein Translated from the Moderna mRNA-1273 Vaccine
5,716 downloads medRxiv allergy and immunology

Timothy Veenstra, Elisha Injeti, Bradley Pauley

Extensive research around mRNA vaccines and their proposed utility during the current COVID-19 pandemic resulted in many publications concerning the SARS-Cov-2 spike protein and angiotensin converting enzyme-2 receptor-binding domain of the virus, but none describe the characteristics of the full-length protein obtained from the modified/synthetic mRNA that is part of the Moderna and Pfizer-BioNTech vaccines. In this paper, we provide the first data characterizing the actual proteins produced by mouse and human cells in culture that had been incubated up to 30 minutes with the commercial vaccine produced by Moderna (i.e., Spikevax). The mRNA vaccine continues to produce proteins up to 12-14 days after introduction to the cells. The molecular weight of the SARS-CoV-2 encoded protein ranges from 135-200 kilodaltons depending on the extent of glycosylation.

20: Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation
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Posted 03 May 2020

Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation
5,500 downloads medRxiv allergy and immunology

Matthew Woodruff, Richard Ramonell, Kevin Cashman, Doan Nguyen, Ankur Saini, Natalie Haddad, Ariel Ley, Shuya Kyu, J. Christina Howell, Tugba Ozturk, Saeyun Lee, Weirong Chen, Jacob Estrada, Andrea Morrison-Porter, Andrew Derrico, Fabliha Anam, Monika Sharma, Henry Wu, Sang Le, Scott Jenks, Christopher M Tipton, Wiliam Hu, F. Eun-Hyung Lee, Ignacio Sanz

A wide clinical spectrum has become a hallmark of the SARS-CoV-2 (COVID-19) pandemic, although its immunologic underpinnings remain to be defined. We have performed deep characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation as previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody secreting cell expansion and early production of high levels of SARS-CoV-2-specific antibodies. Yet, these patients fared poorly with elevated inflammatory biomarkers, multi-organ failure, and death. Combined, the findings strongly indicate a major pathogenic role for immune activation in subsets of COVID-19 patients. Our study suggests that, as in autoimmunity, targeted immunomodulatory therapy may be beneficial in specific patient subpopulations that can be identified by careful immune profiling.

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