Browsing by Department "A-Star, Singapore Immunology Network"
  • Institution Publication
    Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters
    ( 2023-01-01)
    Rouers A.
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    Wong N.
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    Goh Y.S.
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    Torres-Ruesta A.
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    Tay M.Z.
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    Chang Z.W.
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    Fong S.W.
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    Neo V.
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    Kam I.K.J.
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    Yeo N.K.W.
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    Huang Y.
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    Loh C.Y.
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    Hor P.X.
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    Wong J.X.E.
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    Tan Y.J.
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    Macary P.A.
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    Qian X.
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    Bei W.
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    Ngoh E.Z.X.
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    Salleh S.N.M.
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    Wang C.I.
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    Poh X.Y.
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    Rao S.
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    Rao S.
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    Chia P.Y.
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    Chia P.Y.
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    Chia P.Y.
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    Ong S.W.X.
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    Ong S.W.X.
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    Lee T.H.
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    Lee T.H.
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    Lin R.J.H.
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    Lin R.J.H.
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    Lim C.
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    Teo J.
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    Ren E.C.
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    Lye D.C.
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    Lye D.C.
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    Lye D.C.
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    Lye D.C.
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    Young B.E.
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    Young B.E.
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    Young B.E.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
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    Renia L.
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    Renia L.
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    Renia L.
    Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ‘‘BBB”) or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ‘‘BBM”) at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.
  • Institution Publication
    Pathogenic Th1 responses in CHIKV-induced inflammation and their modulation upon Plasmodium parasites co-infection
    ( 2020-03-01)
    Torres-Ruesta A.
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    Torres-Ruesta A.
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    Teo T.H.
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    Teo T.H.
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    Chan Y.H.
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    Rénia L.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
    The induction of polyarthritis and polyarthralgia is a hallmark of arthritogenic alphavirus infections, with an exceptionally higher morbidity observed with chikungunya virus (CHIKV). While the mechanisms underlying these incapacitating acute symptoms remain partially understood, the progression to chronic conditions in some cases remains unanswered. The highly pro-inflammatory nature of alphavirus disease has suggested the involvement of virus-specific, joint-infiltrating Th1 cells as one of the main pathogenic mediators of CHIKV-induced joint pathologies. This review summarizes the role of cell-mediated immune responses in CHIKV pathogenesis, with a specific focus on pro-inflammatory Th1 responses in the development of CHIKV joint inflammation. Furthermore, due to the explosive nature of arthritogenic alphavirus outbreaks and their recent expansion across the world, co-infections with other highly prevalent pathogens such as malaria are likely to occur but the pathological outcomes of such interactions in humans are unknown. This review will also discuss the potential impact of malaria co-infections on CHIKV pathogenesis and their relevance in alphavirus control programs in endemic areas.
  • Institution Publication
    Prolonged inflammation in patients hospitalized for coronavirus disease 2019 (COVID-19) resolves 2 years after infection
    ( 2023-05-01)
    Fong S.W.
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    Goh Y.S.
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    Torres-Ruesta A.
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    Chang Z.W.
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    Chan Y.H.
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    Neo V.K.
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    Lee B.
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    Lee B.
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    Duan K.
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    Amrun S.N.
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    Yeo N.K.W.
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    Chen H.V.
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    Tay M.Z.
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    Carissimo G.
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    Carissimo G.
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    Tan S.Y.
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    Leo Y.S.
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    Leo Y.S.
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    Leo Y.S.
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    Leo Y.S.
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    Lye D.C.
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    Lye D.C.
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    Lye D.C.
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    Lye D.C.
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    Renia L.
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    Renia L.
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    Renia L.
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    Young B.E.
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    Young B.E.
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    Young B.E.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
    Long-term complications from coronavirus disease 2019 (COVID-19) are concerning, as survivors can develop subclinical multiorgan dysfunction. It is unknown if such complications are due to prolonged inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination may reduce sequela. We conducted a prospective longitudinal study on hospitalized patients over 24 months. Clinical symptoms were collected by self-reporting during follow-up, along with blood samples for quantification of inflammatory markers and immune cell frequencies. All patients were given one dose of mRNA vaccine at 12−16 months. Their immune profiles at 12 and 24 months were compared. Approximately 37% and 39% of our patients reported post-COVID-19 symptoms at 12 and 24 months, respectively. The proportion of symptomatic patients with more than one symptom decreased from 69% at 12 months to 56% at 24 months. Longitudinal cytokine profiling revealed a cluster of individuals with persistently high inflammatory cytokine levels 12 months after infection. Patients with prolonged inflammation showed elevated terminally differentiated memory T cells in their blood; 54% had symptoms at 12 months. The majority of inflammatory markers and dysregulated immune cells in vaccinated patients recovered to a healthy baseline at 24 months, even though symptoms persisted. Post-COVID-19 symptoms can linger for 2 years after the initial infection and are associated with prolonged inflammation. Prolonged inflammation in hospitalized patients resolves after 2 years. We define a set of analytes associated with persistent inflammation and presence of symptoms, which could be useful biomarkers for identifying and monitoring high-risk survivors.
  • Institution Publication
    Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection
    ( 2022-02-01)
    Fong S.W.
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    Yeo N.K.W.
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    Chan Y.H.
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    Goh Y.S.
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    Amrun S.N.
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    Ang N.
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    Rajapakse M.P.
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    Lum J.
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    Foo S.
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    Lee C.Y.P.
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    Carissimo G.
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    Chee R.S.L.
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    Torres-Ruesta A.
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    Torres-Ruesta A.
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    Tay M.Z.
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    Chang Z.W.
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    Poh C.M.
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    Young B.E.
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    Young B.E.
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    Young B.E.
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    Tambyah P.A.
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    Tambyah P.A.
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    Tambyah P.A.
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    Kalimuddin S.
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    Kalimuddin S.
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    Leo Y.S.
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    Leo Y.S.
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    Leo Y.S.
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    Leo Y.S.
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    Lye D.C.
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    Lye D.C.
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    Lye D.C.
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    Lye D.C.
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    Lee B.
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    Biswas S.
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    Howland S.W.
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    Renia L.
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    Renia L.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host–pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.
  • Institution Publication
    Viperin controls chikungunya virus-specific pathogenic T cell IFNγ Th1 stimulation in mice
    ( 2019-01-01)
    Carissimo G.
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    Carissimo G.
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    Teo T.H.
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    Teo T.H.
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    Chan Y.H.
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    Chan Y.H.
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    Chan Y.H.
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    Lee C.Y.P.
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    Lee C.Y.P.
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    Lee C.Y.P.
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    Lee B.
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    Lee B.
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    Torres-Ruesta A.
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    Torres-Ruesta A.
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    Torres-Ruesta A.
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    Tan J.J.L.
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    Tan J.J.L.
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    Chua T.K.
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    Chua T.K.
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    Fong S.W.
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    Fong S.W.
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    Fong S.W.
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    Lum F.M.
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    Lum F.M.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
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    Ng L.F.P.
    Chikungunya virus (CHIKV) has been a worldwide threat since its reemergence in La Reunion Island in 2004. Expression of the interferon-stimulated protein Viperin correlates with viral load burden in patients, and studies in mice have demonstrated its role to limit disease severity against CHIKV infection. Using Viperin2/2 mice, we aimed to understand the contribution of Viperin to the T-cell immune response against CHIKV. CD4 T-cell depletion in Viperin2/2 mice showed that increased late acute joint inflammation (5-8 d postinfection) was exclusively mediated by T cells. Specifically, CHIKV-infected Viperin2/2 mice showed an increased INFγ Th1 profile of CD4 T cells, enhanced INFγ stimulation by APCs, an increased INFγ secretion profile in the joint microenvironment, and increased numbers of inflammatory monocytes in virus-infected joints compared with WT mice. Bone marrow grafting experiments showed that Viperin expression in both hematopoietic and non-hematopoietic cells is instrumental in reducing disease severity associated with a CD4 T-cell response.