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Article ; Online: Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concernResearch in context

Aled O’Neill / Chinmay Kumar Mantri / Chee Wah Tan / Wilfried A.A. Saron / Santhosh Kambaiah Nagaraj / Monica Palanichamy Kala / Christy Margarat Joy / Abhay P.S. Rathore / Shashank Tripathi / Lin-Fa Wang / Ashley L. St. John

EBioMedicine, Vol 99, Iss , Pp 104924- (2024)

1481

Abstract: Summary: Background: COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through ... ...

Abstract	Summary: Background: COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. Methods: Here we tested an intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 compared with the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum, in mice, for immunological read-outs. The same formulation delivered I.N. or S.C. was tested in hamsters to assess efficacy. Findings: I.N. vaccination improved systemic T cell responses compared to an equivalent dose of antigen delivered S.C. and T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralising the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralising capacity against multiple variants of concern (VOC), compared to S.C. vaccination. I.N. vaccination provided significant protection from lung pathology compared to unvaccinated animals upon challenge with homologous and heterologous SARS-CoV-2 strains in a hamster model. Interpretation: These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralising antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases. Funding: This study was funded by Duke-NUS Medical School, the Singapore Ministry ...
Keywords	Mucosal vaccine ; T cell ; SARS-CoV-2 ; COVID-19 ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Use of a point-of-care test to rapidly assess levels of SARS-CoV-2 nasal neutralising antibodies in vaccinees and breakthrough infected individuals

Chee Wah Tan / Chuan Kok Lim / Jacqueline Prestedge / Mitchell Batty / Yun Yan Mah / Michelle O’Han / Lin-Fa Wang / Dean Kilby / Danielle E. Anderson

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 13

Abstract: Abstract Despite SARS-CoV-2 vaccines eliciting systemic neutralising antibodies (nAbs), breakthrough infections still regularly occur. Infection helps to generate mucosal immunity, possibly reducing disease transmission. Monitoring mucosal nAbs is ... ...

Abstract	Abstract Despite SARS-CoV-2 vaccines eliciting systemic neutralising antibodies (nAbs), breakthrough infections still regularly occur. Infection helps to generate mucosal immunity, possibly reducing disease transmission. Monitoring mucosal nAbs is predominantly restricted to lab-based assays, which have limited application to the public. In this multi-site study, we used lateral-flow surrogate neutralisation tests to measure mucosal and systemic nAbs in vaccinated and breakthrough infected individuals in Australia and Singapore. Using three lateral flow assays to detect SARS-CoV-2 nAbs, we demonstrated that nasal mucosal nAbs were present in 71.4 (95% CI 56.3–82.9%) to 85.7% (95% CI 71.8–93.7%) of individuals with breakthrough infection (positivity rate was dependent upon the type of test), whereas only 20.7 (95% CI 17.1–49.4%) to 34.5% (95% CI 19.8–52.7%) of vaccinated individuals without breakthrough infection had detectible nasal mucosal nAbs. Of the individuals with breakthrough infection, collective mucosal anti-S antibody detection in confirmatory assays was 92.9% (95% CI 80.3–98.2%) of samples, while 72.4% (95% CI 54.1–85.5%) of the vaccinated individuals who had not experienced a breakthrough infection were positive to anti-S antibody. All breakthrough infected individuals produced systemic anti-N antibodies; however, these antibodies were not detected in the nasal cavity. Mucosal immunity is likely to play a role in limiting the transmission of SARS-CoV-2 and lateral flow neutralisation tests provide a rapid readout of mucosal nAbs at the point-of-care.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years

Chee Fu Yung / Nina Le Bert / Kai Qian Kam / Seyed Ehsan Saffari / Chee Wah Tan / Yun Yan Mah / Jinyan Zhang / Aileen Ying-Yan Yeoh / Feng Zhu / Smrithi Hariharaputran / Chia Yin Chong / Antonio Bertoletti / Linfa Wang

Scientific Reports, Vol 13, Iss 1, Pp 1-

a cohort study

2023 Volume 8

Abstract: Abstract There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) ... ...

Abstract	Abstract There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5–11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR 16.5–30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Low neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: WHO international standard for SARS-CoV-2 antibodies to determine markers of protection

Feng Zhu / Thomas Althaus / Chee Wah Tan / Alizée Costantini / Wan Ni Chia / Nguyen Van Vinh Chau / Le Van Tan / Giada Mattiuzzo / Nicola J Rose / Eric Voiglio / Lin-Fa Wang

The Lancet Microbe, Vol 3, Iss 2, Pp e81-e

2022 Volume 82

Keywords	Medicine (General) ; R5-920 ; Microbiology ; QR1-502
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dynamics of Neutralizing Antibody and T-Cell Responses to SARS-CoV-2 and Variants of Concern after Primary Immunization with CoronaVac and Booster with BNT162b2 or ChAdOx1 in Health Care Workers

Watsamon Jantarabenjakul / Pimpayao Sodsai / Napaporn Chantasrisawad / Anusara Jitsatja / Sasiprapa Ninwattana / Nattakarn Thippamom / Vichaya Ruenjaiman / Chee Wah Tan / Rakchanok Pradit / Jiratchaya Sophonphan / Supaporn Wacharapluesadee / Lin-Fa Wang / Thanyawee Puthanakit / Nattiya Hirankarn / Opass Putcharoen

Vaccines, Vol 10, Iss 639, p

2022 Volume 639

Abstract: Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declines within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster ... ...

Abstract	Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declines within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants who received ChAdOx1 and forty-two participants who received BNT162b2 were enrolled into this study, which evaluated immune responses, including anti-SARS-CoV-2 spike total antibodies (Elecsys ® ), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript), five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization, as well as 4 and 12 weeks after receiving the booster. This study showed a significant increase in anti-SARS-CoV-2 spike total antibodies, sVNT, and T-cell immune response after the booster, including against the Omicron variant. Immune responses rapidly decreased in the booster group at 12 weeks after booster but were still higher than post-primary vaccination. A fourth dose or a second booster should be recommended, particularly in health care workers.
Keywords	COVID-19 ; SARS-CoV-2 ; vaccines ; anti-SARS-CoV-2 spike total antibodies ; surrogate viral neutralizing antibody ; T-cell immune response ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections

Kevin J. Selva / Pradhipa Ramanathan / Ebene R. Haycroft / Arnold Reynaldi / Deborah Cromer / Chee Wah Tan / Lin-Fa Wang / Bruce D. Wines / P. Mark Hogarth / Laura E. Downie / Samantha K. Davis / Ruth A. Purcell / Helen E. Kent / Jennifer A. Juno / Adam K. Wheatley / Miles P. Davenport / Stephen J. Kent / Amy W. Chung

JCI Insight, Vol 8, Iss

2023 Volume 18

Abstract: Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from ... ...

Abstract	Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19–recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19–recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19–uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2–specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2–specific antibody responses and has implications for long-term protection from COVID-19.
Keywords	COVID-19 ; Medicine ; R
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Early detection of neutralizing antibodies against SARS-CoV-2 in COVID-19 patients in Thailand.

Opass Putcharoen / Supaporn Wacharapluesadee / Wan Ni Chia / Leilani Paitoonpong / Chee Wah Tan / Gompol Suwanpimolkul / Watsamon Jantarabenjakul / Chanida Ruchisrisarod / Phanni Wanthong / Jiratchaya Sophonphan / Pajaree Chariyavilaskul / Lin-Fa Wang / Thiravat Hemachudha

PLoS ONE, Vol 16, Iss 2, p e

2021 Volume 0246864

Abstract: Background The presence of neutralizing antibodies (NAbs) is an indicator of protective immunity for most viral infections. A newly developed surrogate viral neutralization assay (sVNT) offers the ability to detect total receptor binding domain-targeting ...

Abstract	Background The presence of neutralizing antibodies (NAbs) is an indicator of protective immunity for most viral infections. A newly developed surrogate viral neutralization assay (sVNT) offers the ability to detect total receptor binding domain-targeting NAbs in an isotype-independent manner, increasing the test sensitivity. Thus, specimens with low IgM/ IgG antibody levels showed strong neutralization activity in sVNT. Methods This study aimed to measure the %inhibition of NAbs measured by sVNT in PCR-confirmed COVID-19 patients. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection and its kinetics were determined. Results Ninety-seven patients with PCR-confirmed SARS-CoV-2 infection were included in this study. Majority of the patients were 21-40 years old (67%) and 63% had mild symptoms. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection was 99% (95% confidence interval (CI) 94.4-100%) and the specificity was 100% (95% CI 98.3-100%). The negative predictive value of sVNT from the samples collected before and after 7 days of symptom onset was 99.5% (95% CI 97.4-100%) and 100% (95% CI 93.8-100%), respectively. The level of inhibition at days 8-14 were significantly higher than days 0-7 (p<0.001). The median %inhibition values by severity of COVID-19 symptoms were 79.9% (interquartile range (IQR) 49.7-91.8%); 89.0% (IQR 71.2-92.4%); and 86.6% (IQR 69.5-92.8%), for mild, moderate and severe/critical symptoms respectively. The median level of sVNT %inhibition of severe was significantly higher than the mild group (p = 0.05). Conclusion The sVNT is a practical and robust serological test for SARS-CoV-2 infection and does not require specialized biosafety containment. It can be used clinically to aid diagnosis in both early and late infection especially in cases when the real-time RT-PCR results in weakly negative or weakly positive, and to determine the protective immune response from SARS-CoV-2 infection in patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness

Chandima Jeewandara / Deshni Jayathilaka / Laksiri Gomes / Ananda Wijewickrama / Eranga Narangoda / Damayanthi Idampitiya / Dinuka Guruge / Ruwan Wijayamuni / Suranga Manilgama / Graham S. Ogg / Chee Wah Tan / Lin-Fa Wang / Gathsaurie Neelika Malavige

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV-2 neutralizing antibodies (NAbs), and their association with clinical disease ... ...

Abstract	Abstract In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV-2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points. Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p = 0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had NAbs, 38/76 (50%) in those with > 90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (> 90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Yidan Wang / Ying Xu / Chee Wah Tan / Longliang Qiao / Wan Ni Chia / Hongyi Zhang / Qin Huang / Zhenqiang Deng / Ziwei Wang / Xi Wang / Xurui Shen / Canyu Liu / Rongjuan Pei / Yuanxiao Liu / Shuai Xue / Deqiang Kong / Danielle E. Anderson / Fengfeng Cai / Peng Zhou /

Lin-Fa Wang / Haifeng Ye

Nature Communications, Vol 14, Iss 1, Pp 1-

Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice

2023 Volume 1

Keywords	Science ; Q
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Infection of human Nasal Epithelial Cells with SARS-CoV-2 and a 382-nt deletion isolate lacking ORF8 reveals similar viral kinetics and host transcriptional profiles.

Akshamal M Gamage / Kai Sen Tan / Wharton O Y Chan / Jing Liu / Chee Wah Tan / Yew Kwang Ong / Mark Thong / Anand K Andiappan / Danielle E Anderson / De Yun Wang / Lin-Fa Wang

PLoS Pathogens, Vol 16, Iss 12, p e

2020 Volume 1009130

Abstract: The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding of the host immune response to SARS-CoV-2 is still in its infancy. A 382-nt deletion strain ... ...

Abstract	The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding of the host immune response to SARS-CoV-2 is still in its infancy. A 382-nt deletion strain lacking ORF8 (Δ382 herein) was isolated in Singapore in March 2020. Infection with Δ382 was associated with less severe disease in patients, compared to infection with wild-type SARS-CoV-2. Here, we established Nasal Epithelial cells (NECs) differentiated from healthy nasal-tissue derived stem cells as a suitable model for the ex-vivo study of SARS-CoV-2 mediated pathogenesis. Infection of NECs with either SARS-CoV-2 or Δ382 resulted in virus particles released exclusively from the apical side, with similar replication kinetics. Screening of a panel of 49 cytokines for basolateral secretion from infected NECs identified CXCL10 as the only cytokine significantly induced upon infection, at comparable levels in both wild-type and Δ382 infected cells. Transcriptome analysis revealed the temporal up-regulation of distinct gene subsets during infection, with anti-viral signaling pathways only detected at late time-points (72 hours post-infection, hpi). This immune response to SARS-CoV-2 was significantly attenuated when compared to infection with an influenza strain, H3N2, which elicited an inflammatory response within 8 hpi, and a greater magnitude of anti-viral gene up-regulation at late time-points. Remarkably, Δ382 induced a host transcriptional response nearly identical to that of wild-type SARS-CoV-2 at every post-infection time-point examined. In accordance with previous results, Δ382 infected cells showed an absence of transcripts mapping to ORF8, and conserved expression of other SARS-CoV-2 genes. Our findings shed light on the airway epithelial response to SARS-CoV-2 infection, and demonstrate a non-essential role for ORF8 in modulating host gene expression and cytokine production from infected cells.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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