- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- Mosquito-borne diseases and control
- Malaria Research and Control
- Eosinophilic Esophagitis
- SARS-CoV-2 detection and testing
- Asthma and respiratory diseases
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- Vaccine Coverage and Hesitancy
- Viral Infections and Vectors
- Long-Term Effects of COVID-19
- Eosinophilic Disorders and Syndromes
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- Bacteriophages and microbial interactions
- Bacterial Infections and Vaccines
- Urticaria and Related Conditions
- Peptidase Inhibition and Analysis
- Calcium signaling and nucleotide metabolism
Agency for Science, Technology and Research
2019-2024
Singapore Immunology Network
2019-2023
A*STAR Graduate Academy
2021-2022
National University of Singapore
2022
Sorbonne Université
2014-2019
Centre d'Immunologie et des Maladies Infectieuses
2014-2019
Sorbonne Paris Cité
2019
Inserm
2014-2017
Centre National de la Recherche Scientifique
2015-2017
Abstract Understanding the impact of age on vaccinations is essential for design and delivery vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis multiple compartments memory immune response in 312 individuals vaccinated with BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody T cell responses most individuals. However, recognition Spike protein Delta Omicron variants less efficient than that ancestral Wuhan strain. Age-stratified...
Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered differentiation Tfh isolated from lymph nodes HIV-infected (HIV+) individuals provide inadequate help in vitro. However, the mechanisms underlying this impairment function are not fully defined. Using a unique collection splenocytes, we compared frequency, phenotype transcriptome subsets spleens HIV negative...
Abstract It is widely assumed that CD4+ T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)–restricted Ags have been described, in particular epitopes newly synthesized proteins (so-called endogenous). In this study, we show HIV-infected dendritic (DC) present MHC-II–restricted endogenous to HIV-specific (HS) cells. This pathway functions independently the exogenous route...
Regulatory T cells (Tregs) play a major role in immune homeostasis and the prevention of autoimmune diseases. It has been shown that c-Rel is critical Treg thymic differentiation, but little known on NF-κB mature biology. We thus generated mice with specific knockout RelA, key member NF-κB, Tregs. These developed severe syndrome multi-organ infiltration high activation lymphoid myeloid cells. Phenotypic transcriptomic analyses showed RelA acquisition effector state independently surrounding...
Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different serotypes. We provide here a systematic, longitudinal analysis of B cell, T antibody responses in the same patients. Antibody as well cell activation differentiate primary from secondary responses. Hospitalization is associated lower frequencies activated, terminally differentiated cells higher percentages effector memory CD4 cells. Patients more severe...
The emergence of new SARS-CoV-2 variants, such as the more transmissible Delta and Omicron has raised concerns on efficacy COVID-19 vaccines. Here, we examined waning antibody responses against different variants following primary booster vaccination. We found that were low response was almost non-existent. Efficient boosting all including Omicron, observed a third dose. tested significantly higher at one month vaccination, compared with two months for individuals, responders identified...
CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play a major role in peripheral tolerance. Multiple environmental factors and cell types affect their biology. Among them, activated effector CD4(+) can boost Treg expansion through TNF or IL-2. In this study, we further characterized (Teff) cell-dependent vivo mice. This phenomenon was observed when both Teff were by cognate Ag, with the latter being same different. Also, highly proliferated on own, there no additional cells. condition of low...
SARS-CoV-2 was first detected in late December 2019, however, the few months that followed, resultant COVID-19 disease has developed into a devastating pandemic around world [[1]https://covid19.who.int/.Google Scholar]. This led to race produce safe and efficacious vaccine record time. In less than year, BNT162b2, an mRNA-based by BioNTech-Pfizer [[2]Polack FP Thomas SJ Kitchin N et al.Safety efficacy of BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus...
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also HIV controllers that repress HIV-1 replication. In these elite (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the correlates associated generation of bnAbs may help in designing efficient immunotherapies. this study, ECs either positive or negative for HLA-B*57 protective allele, treated HIV-infected...
A variety of signals influence the capacity dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C-type lectines, influences DC biology affects their susceptibility HIV infection. Yet, whether combined effects PPRs triggering infection HIV-specific (HS) CTL responses remain enigmatic. Here, we dissect impact receptors on maturation, infection, quality HS activation....
Background: On 26 November 2021, the World Health Organization designated B.1.1.529 lineage of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as fifth variant concern, Omicron. Infections have quickly spread worldwide but understanding viral dynamics and cytokine cellular immunological response during infection remain limited. Methods: Detailed patient-level data from 174 age-matched patients with sequence confirmed Omicron or Delta (87 each group) admitted to National Centre...
Clinically important broadly reactive B cells evolve during multiple infections, with re-activated after secondary infection differing from activated a primary infection. Here we studied CD27highCD38high plasmablasts patients or dengue virus Three transcriptionally and functionally distinct clusters were identified. The largest cluster 0/1 was plasma cell-related, coding for serotype cross-reactive antibodies of the IgG1 isotype, consistent memory cell activation an extrafollicular response....
Abstract Background On 26 November 2021, the World Health Organization designated B.1.1.529 lineage of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as fifth variant concern, Omicron. Infections have quickly spread worldwide, but understanding viral dynamics and cytokine cellular immunological response during infection remain limited. Methods Detailed patient-level data from 174 age-matched patients with sequence confirmed Omicron or Delta admitted to National Centre for...
Adoptive cell therapy represents a promising approach for several chronic diseases. This study describes an innovative strategy biofunctionalization of nanoparticles, allowing the generation synthetic particulate antigens (SPAg). SPAg activate polyclonal B cells and vectorize noncognate proteins into their endosomes, generating highly efficient stimulators ex vivo expansion antigen-specific CD4+ T cells. method also allows harnessing ability to polarize effectors or regulators.
B-cell ELISpot is an extremely sensitive assay based on the secretion of antibodies by B cells that requires differentiation into antibody-secreting cells. Here, we describe procedure to analyze both plasmablast (PB) and memory cell (MBC) responses specific SARS-CoV-2 receptor-binding domain (RBD) in context acute infection vaccination. We detail steps for MBC stimulation, PB plating, detection, counting total IgG RBD-specific spots. For complete details use execution this protocol, please...
Abstract Objective Despite the high vaccine efficacy of mRNA COVID‐19 vaccines, there are individuals who developed excessive reactogenic and/or allergic responses after first dose and were considered ineligible for further doses. CoronaVac, an inactivated SARS‐CoV‐2 vaccine, is recommended in Singapore as alternative. Methods Individuals, vaccines (BNT162b2 or mRNA‐1273) because reactive to prime vaccination, recruited offered two doses CoronaVac booster vaccination 38–224 days post their...
Abstract Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the emergence of variants concern highlight need for booster vaccinations. This is particularly important elderly population, who are at a higher risk developing disease 2019 (COVID‐19) disease. While studies have shown increased responses following vaccination, understanding changes in T B cell compartments induced by third vaccine dose remains limited. We analyzed humoral cellular...
The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development employment new functional assay measures antibodies present longitudinal data illustrating impact age, sex comorbidities on kinetics strength vaccine-induced key in an Asian volunteer cohort. We also accurate quantitation exploits unique set in-house,...
Abstract Efficient COVID-19 vaccines have been developed in record time. Here, we present findings from a comprehensive and integrated analysis of multiple compartments the memory immune response 312 individuals vaccinated with BNT162b2 mRNA vaccine. Two vaccine doses induced high antibody T cell responses most individuals. However, recognition Spike protein delta variant was less efficient than that Wuhan strain. Age stratified analyses identified group low responders where ≥ 60 years were...
Abstract Background The emergence of rapidly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, coupled with waning vaccine-induced immunity, has contributed to the rise vaccine breakthrough infections. It is crucial understand how protection mediated. Methods We examined prospective cohorts mRNA vaccinated and boosted individuals during Omicron wave infection in Singapore. Results found that who remain uninfected over follow-up period had a higher...