Publications by authors named "Lin-Fa Wang"

We describe isolation and characterization of a novel henipavirus, designated Salt Gully virus, from the urine of pteropid bats in Australia. We noted the virus to be most closely related to Angavokely virus, not reliant on ephrin receptors for cell entry, and of unknown risk for human disease.

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Community-based serosurveillance for emerging zoonotic viruses can provide a powerful and cost-effective measurement of cryptic spillovers. Betacoronaviruses, including SARS-CoV, SARS-CoV-2 and MERS-CoV, are known to infect bats and can cause severe respiratory illness in humans, yet remain under-surveyed in high-risk populations. This study aimed to determine the seroprevalence of betacoronaviruses in an occupational cohort in contact with bats before and after the emergence of SARS-CoV-2.

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Bats as the only flying mammals incur a high metabolic cost during extended powered flight, which results in febrile-like temperatures without injury. Herein, we investigate the in vivo heat shock response (HSR) in the cave nectar bat Eonycteris spelaea. We demonstrate that E.

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Antibodies play a crucial role in protection against SARS-CoV-2. Understanding the correlation between binding and functional antibodies is essential to determine whether binding antibody levels can reliably predict neutralizing activity. We assessed antibody responses in 111 individuals vaccinated with the inactivated vaccine CoronaVac and 111 COVID-19 patients in Thailand.

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Several bat species live >20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Artibeus jamaicensis - spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence, express active telomerase, and show attenuated SIPs with dampened secretory phenotype.

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People living with HIV (PLWH) exhibit heterogeneous immune responses, influenced by varying degrees of immune deficiency and viral suppression. The efficacy of COVID-19 vaccines in this population remains underexplored, particularly in those with low CD4 counts. This study assessed the antibody response in PLWH with CD4 T-cell levels ≤200 cells/mm3 compared to those with higher levels, following a bivalent mRNA COVID-19 vaccine booster.

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Introduction: We report Singapore's convalescent plasma (CP) programme during the first year of the COVID-19 pandemic. Based on historical data and its potential therapeutic promise, CP was offered as an experimental treatment option for severe or high-risk COVID-19 patients when established therapeutics were lacking.

Methods: The CP programme was implemented under monitored expanded access approved by Singapore's Ministry of Health.

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Bats are a natural reservoir for a wide variety of notorious viruses that are deadly to humans and other mammals but cause no or minimal clinical damage in bats. The co-evolution of bats and viruses for more than sixty million years has established unique and balanced immune defenses within bats against a number of viruses. With the COVID-19 pandemic, bats have gained greater attention as a likely reservoir of the SARS-CoV-2 ancestor virus.

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Background: Crimean-Congo hemorrhagic fever is a tick-borne zoonotic disease that may be severe and is present in many African countries. We aimed to understand the seroprevalence and risk for Crimean-Congo hemorrhagic fever virus in Tanzania by testing archived serum samples from patients enrolled in a prospective cohort study.

Methods: We prospectively enrolled febrile inpatients and outpatients from 2012 through 2014 at two referral hospitals in northern Tanzania.

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The COVID-19 pandemic highlighted the critical need for well-established clinical research networks capable of rapid response during infectious disease outbreaks. In Southeast Asia, the absence of active research networks at the onset of the COVID-19 contributed to gaps in regional preparedness. This manuscript discusses the challenges and opportunities identified during a regional workshop held in Singapore (February 26 to March 1, 2024), which brought together 130 stakeholders from across the region.

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Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical framework and a large sequence data set from bat-CoVs (including 589 novel CoV sequences) in China to study their macroevolution, cross-species transmission and dispersal.

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We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

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Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Although it is unconfirmed whether pangolins or other traded wildlife served as intermediate hosts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the trafficking of pangolins presents a clear risk for transmission of viruses with zoonotic and epizootic potential regardless. We have investigated the origins of pangolin carcasses seized in Hong Kong and have evaluated their potential exposure to SARSr-CoVs, other coronaviruses, and paramyxoviruses, aiming to address a gap in our knowledge with regard to the role of wildlife trade in the maintenance and emergence of pathogens with zoonotic and epizootic potential.

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Background: A periurban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016 to 2019 at hospitals serving the epizootic area.

Methods: From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at 2 hospitals in Moshi, Tanzania.

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Dynamic pathogen exposure may impact the immunological response to SARS-CoV-2 (SCV2). One potential explanation for the lack of severe SCV2-related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2-related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat-to-human spillover exposures in the region.

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Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation.

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Asia remains vulnerable to new and emerging infectious diseases. Understanding how to improve next generation sequencing (NGS) use in pathogen surveillance is an urgent priority for regional health security. Here we developed a pathogen genomic surveillance assessment framework to assess capacity in low-resource settings in South and Southeast Asia.

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Background: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine.

Methods: We conducted a randomized, participant-blinded, controlled trial.

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Among their many unique biological features, bats are increasingly recognized as a key reservoir of many emerging viruses that cause massive morbidity and mortality in humans. Bats are capable of harboring many of these deadly viruses without any apparent signs of pathology, in a mechanism known as viral disease tolerance. However, the immunological mechanisms behind viral tolerance remain poorly understood.

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Article Synopsis
  • - A study evaluated the immune responses from two types of booster vaccinations (homologous BNT162b2 and heterologous mRNA-1273) in individuals who had previously received BNT162b2 and had not been infected with SARS-CoV-2.
  • - The results showed that those who received the heterologous booster had significantly higher antibody levels against wild-type SARS-CoV-2 six months after vaccination, and many participants experienced Omicron breakthrough infections regardless of the booster type.
  • - The findings suggest that while booster shots are beneficial, the immune response decreases significantly over time, highlighting the need for timely booster administration before infection surges. !*
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Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells.

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