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Article ; Online: Phage ImmunoPrecipitation Sequencing (PhIP-Seq)

Charles Kevin Tiu / Feng Zhu / Lin-Fa Wang / Ruklanthi de Alwis

Pathogens, Vol 11, Iss 568, p

The Promise of High Throughput Serology

2022 Volume 568

Abstract: Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a high throughput serological technology that is revolutionizing the manner in which we track antibody profiles. In this review, we mainly focus on its application to viral infectious diseases. Through ... ...

Abstract	Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a high throughput serological technology that is revolutionizing the manner in which we track antibody profiles. In this review, we mainly focus on its application to viral infectious diseases. Through the pull-down of patient antibodies using peptide-tile-expressing T7 bacteriophages and detection using next-generation sequencing (NGS), PhIP-Seq allows the determination of antibody repertoires against peptide targets from hundreds of proteins and pathogens. It differs from conventional serological techniques in that PhIP-Seq does not require protein expression and purification. It also allows for the testing of many samples against the whole virome. PhIP-Seq has been successfully applied in many infectious disease investigations concerning seroprevalence, risk factors, time trends, etiology of disease, vaccinology, and emerging pathogens. Despite the inherent limitations of this technology, we foresee the future expansion of PhIP-Seq in both investigative studies and tracking of current, emerging, and novel viruses. Following the review of PhIP-Seq technology, its limitations, and applications, we recommend that PhIP-Seq be integrated into national surveillance programs and be used in conjunction with molecular techniques to support both One Health and pandemic preparedness efforts.
Keywords	phage-immunoprecipitation sequencing ; PhIP-Seq ; sero-epidemiology ; phage ; antibody ; diagnostic ; Medicine ; R
Subject code	000
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic Mining Reveals Deep Evolutionary Relationships between Bornaviruses and Bats

Jie Cui / Lin-Fa Wang

Viruses, Vol 7, Iss 11, Pp 5792-

2015 Volume 5800

Abstract: Bats globally harbor viruses in order Mononegavirales, such as lyssaviruses and henipaviruses; however, little is known about their relationships with bornaviruses. Previous studies showed that viral fossils of bornaviral origin are embedded in the ... ...

Abstract	Bats globally harbor viruses in order Mononegavirales, such as lyssaviruses and henipaviruses; however, little is known about their relationships with bornaviruses. Previous studies showed that viral fossils of bornaviral origin are embedded in the genomes of several mammalian species such as primates, indicative of an ancient origin of exogenous bornaviruses. In this study, we mined the available 10 bat genomes and recreated a clear evolutionary relationship of endogenous bornaviral elements and bats. Comparative genomics showed that endogenization of bornaviral elements frequently occurred in vesper bats, harboring EBLLs (endogenous bornavirus-like L elements) in their genomes. Molecular dating uncovered a continuous bornavirus-bat interaction spanning 70 million years. We conclude that better understanding of modern exogenous bornaviral circulation in bat populations is warranted.
Keywords	genomic mining ; endogenous bornaviruses ; bats ; virus-host interaction ; Microbiology ; QR1-502 ; Science ; Q
Language	English
Publishing date	2015-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 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: A strategy to assess spillover risk of bat SARS-related coronaviruses in Southeast Asia

Cecilia A. Sánchez / Hongying Li / Kendra L. Phelps / Carlos Zambrana-Torrelio / Lin-Fa Wang / Peng Zhou / Zheng-Li Shi / Kevin J. Olival / Peter Daszak

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 12

Abstract: Coronaviruses may spill over from bats to humans. This study uses epidemiological data, species distribution models, and probabilistic risk assessment to map overlap among people and SARSr-CoV bat hosts and estimate how many people are infected with bat- ... ...

Abstract	Coronaviruses may spill over from bats to humans. This study uses epidemiological data, species distribution models, and probabilistic risk assessment to map overlap among people and SARSr-CoV bat hosts and estimate how many people are infected with bat-origin SARSr-CoVs in Southeast Asia annually.
Keywords	Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
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: Deconvoluting virome-wide antibody epitope reactivity profiles

Daniel R. Monaco / Sanjay V. Kottapalli / Florian P. Breitwieser / Danielle E. Anderson / Limin Wijaya / Kevin Tan / Wan Ni Chia / Kai Kammers / Patrizio Caturegli / Kathleen Waugh / Mario Roederer / Michelle Petri / Daniel W. Goldman / Marian Rewers / Lin-Fa Wang / H. Benjamin Larman

EBioMedicine, Vol 75, Iss , Pp 103747- (2022)

1479

Abstract: Summary: Background: Comprehensive characterization of exposures and immune responses to viral infections is critical to a basic understanding of human health and disease. We previously developed the VirScan system, a programmable phage-display ... ...

Abstract	Summary: Background: Comprehensive characterization of exposures and immune responses to viral infections is critical to a basic understanding of human health and disease. We previously developed the VirScan system, a programmable phage-display technology for profiling antibody binding to a library of peptides designed to span the human virome. Previous VirScan analytical approaches did not carefully account for antibody cross-reactivity among sequences shared by related viruses or for the disproportionate representation of individual viruses in the library. Methods: Here we present the AntiViral Antibody Response Deconvolution Algorithm (AVARDA), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection with species-level resolution by considering sequence alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. We further assessed AVARDA's utility in associating viral infection with type 1 diabetes and lupus. Findings: By comparing acute and convalescent sera, AVARDA successfully confirmed or detected encephalitis-associated responses to human herpesviruses 1, 3, 4, 5, and 6, improving the rate of diagnosing viral encephalitis in this cohort by 44%. AVARDA analyses of VirScan data from the type 1 diabetes and lupus cohorts implicated enterovirus and herpesvirus infections, respectively. Interpretation: AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases. Funding: This work was made possible by support from the National Institutes of Health (NIH), the US Army Research Office, the Singapore Infectious Diseases Initiative (SIDI), the Singapore Ministry of Health's National Medical Research Council (NMRC) and the Singapore National Research Foundation (NRF).
Keywords	Phage ImmunoPrecipitation Sequencing (PhIP-Seq) ; VirScan ; Encephalitis ; Type 1 diabetes ; Systemic lupus erythematosus ; Antibody profiling ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 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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