Angeline Rouers

Agency for Science, Technology and Research (A*STAR) | A*Star · Infectious Diseases Labs

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. Fifty mRNA-vaccinated participants were enr...

Summary Background Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. Methods We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) vers...

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 and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present lon...

Identification of the risk factors and the high-risk groups which are most vulnerable is critical in COVID-19 disease management at a population level. Evaluating the efficacy of vaccination against infections is necessary to determine booster vaccination strategies for better protection in high-risk groups. In this study, we recruited 158 mRNA-vac...

Vaccine immunogenicity in transplant recipients can be impacted by the immunosuppressive (IS) regimens they receive. While BNT162b2 vaccination has been shown to induce an immune response in liver transplant recipients (LTRs), it remains unclear how different IS regimens may affect vaccine immunogenicity after a third BNT162b2 dose in LTRs, which i...

Dengue non-structural protein (NS1) is an important diagnostic marker during the acute phase of infection. Because NS1 is partially conserved across the flaviviruses, a highly specific DENV NS-1 diagnostic test is needed to differentiate dengue infection from Zika virus (ZIKV) infection. In this study, we characterized three newly isolated antibodi...

B-cell ELISpot is an extremely sensitive assay based on the secretion of antibodies by B cells that requires the differentiation of B cells into antibody-secreting cells. Here, we describe the procedure to analyze both plasmablast (PB) and memory B cell (MBC) responses specific to SARS-CoV-2 receptor-binding domain (RBD) in the context of acute SAR...

The emergence of new SARS-CoV-2 variants, such as the more transmissible Delta and Omicron variants, has raised concerns on efficacy of the COVID-19 vaccines. Here, we examined the waning of antibody responses against different variants following primary and booster vaccination. We found that antibody responses against variants were low following p...

Waning antibody levels against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) and the emergence of variants of concern (VOC) 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. Whilst studies h...

Objective: Despite the high vaccine efficacy of mRNA COVID-19 vaccines, there are individuals who developed excessive reactogenic and/or allergic responses after the first mRNA dose and were considered ineligible for further mRNA doses. CoronaVac, an inactivated SARS-CoV-2 vaccine, is recommended in Singapore as an alternative. Methods: Individu...

Understanding the impact of age on vaccinations is essential for the design and delivery of vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody and T...

Background On 26 November 2021, the World Health Organization designated the B.1.1.529 lineage of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the fifth variant of concern, Omicron. Infections have quickly spread worldwide, but understanding of the viral dynamics and the cytokine and cellular immunological response during infecti...

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against...

Efficient COVID-19 vaccines have been developed in record time. Here, we present findings from a comprehensive and integrated analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 mRNA vaccine. Two vaccine doses induced high antibody and T cell responses in most individuals. However, antibod...

Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiate primary...

Clinically important broadly reactive B cells evolve during multiple infections, with B cells re-activated after secondary infection differing from B cells activated after a primary infection. Here we studied CD27highCD38high plasmablasts from patients with a primary or secondary dengue virus infection. Three transcriptionally and functionally dist...

T cells play important multifaceted roles during dengue infection, and understanding their responses is important for defining correlates of protective immunity and identifying effective vaccine antigens. Using mass cytometry and a highly multiplexed peptide-HLA (human leukocyte antigen) tetramer staining strategy, we probed T cells from dengue pat...

Regulatory T cells (Tregs) play a major role in immune homeostasis and in the prevention of autoimmune diseases. It has been shown that c-Rel is critical in Treg thymic differentiation, but little is known on the role of NF-κB on mature Treg biology. We thus generated mice with a specific knockout of RelA, a key member of NF-κB, in Tregs. These mic...

Follicular helper T cells (Tfh) have been discovered in lymph nodes and, since then, are the focus of very intensive research to understand their origin, differentiation and functions. Tfh interact with B cells in the secondary lymphoid organs leading to B cell differentiation and maturation. Tfh are particularly studied in pathological contexts su...

Proportions of memory B cell populations in HIV+ patients and HIV − donors. (a) Frequency of total memory B cells (CD27+ IgD −) among CD19+ B cells. (b) Frequency of naïve B cells (CD27 − IgD+) among CD19+ B cells. (c) Frequency of IgG + cells among memory B cells. (d) Frequency of IgG2+ cells among memory B cells. (e) Frequency of CD38hi plasmabla...

Distribution and frequency of B cells according to their Ab isotype in HIV+ and HIV − donors. Frequencies of B cells secreting IgG (a), IgG1 (b), IgG2 (c) or IgG3 (d) among total B cells in EC (circle: HLA-B*57+ or square: HLA-B*57 −), cART and HIV-negative donors. Each individual is represented by a specific dot on each graph (shape and color). St...

Memory B cell responses against Influenza vaccine antigens. Frequency of Flu-specific IgG+ B cells in EC, cART and HIV-negative donors. Each individual is represented by a specific dot on each graph (shape and color). Circle: HLA-B*57+ EC; square: HLA-B*57 − EC. Statistical significance was calculated using a Kruskal-Wallis test followed by a Dunn’...

Proportion of HLA-B57+ and HLA-B57 − EC responding to viral antigens. HLA-B57+ EC (n = 16) are represented in green and HLA-B*57 − (n = 17) in orange. Proportions of patient presenting (a) IgG +, (b) IgG1 +, (c) IgG2 + and (d) IgG3 + B cell responses against HIV-Env antigens (gp140Yu2b, gp41S30 or gp160THO) and Influenza vaccine antigens (Flu, VAXI...

Phenotypic analysis of circulating B cell populations using flow cytometry. B cells were identified using CD19, and further subdivided in naïve (CD27–IgD+), total memory B cells (CD27+ IgD–), activated memory (AM, CD27+ CD21 −), resting memory (RM, CD27+ CD21+), intermediate memory (IM, CD27− CD21+), tissue-like memory (TLM, CD27 − CD21 −), plasmab...

The quantity of HIV-specific IgG in patient’s sera does not correlate with HIV-specific B cell frequency. (a) Quantity of HIV-specific IgG normalized to total IgG, evaluated using gp41 and gp140 HIV antigens, in sera from HLA-B*57 + (yellow circles) and HLA-B*57 − (pink squares) EC. Bars indicate median values. (b) Spearman correlation between the...

A fraction of HIV-1-infected individuals (so-called elite controllers, ECs) naturally control HIV-1 replication maintaining undetectable viral loads. Understanding the mechanisms implicated in natural control of HIV-1 infection will help in developing efficient HIV vaccines. In ECs, we analyzed the influence of B cell antibody responses. We show th...

The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-i...

La réponse humorale est altérée lors de l’infection par le virus de l’immunodéficience humaine (VIH). Les lymphocytes T CD4+ folliculaires helper (Tfh) sont impliqués dans la maturation des lymphocytes B (LB) dans les organes lymphoïdes secondaires. Mon travail de thèse s’est articulé autour de deux axes complémentaires visant à étudier les Tfh et...

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 derived from newly synthesized proteins (so-called endogenous). In this study, we show...

(75 words max) Adoptive cell therapy represents a promising approach for several chronic diseases. This study describes an innovative strategy for biofunctionalization of nanoparticles, allowing the generation of synthetic particulate antigens (SPAg). SPAg activate polyclonal B cells and vectorize non-cognate proteins into their endosomes, generati...

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 B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlyi...

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(+) T cells can boost Treg cell expansion through TNF or IL-2. In this study, we further characterized this effector T (Teff) cell-dependent Treg cell boost...