Publications by authors named "Wen S Lee"

Background: The immunogenicity of current influenza vaccines need improvement. Inactivated influenza and COVID-19 mRNA vaccines can be co-administered but randomized controlled trial data is lacking on whether the two vaccines are more immunogenic if given in the same or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when co-formulated and delivered together.

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Recombinant influenza viruses are promising vectors that can bolster antibody and resident lymphocyte responses within mucosal sites. This study evaluates recombinant influenza viruses with SARS-CoV-2 RBD genes in eliciting mucosal and systemic responses. Using reverse genetics, we generated replication-competent recombinant influenza viruses carrying heterologous RBD genes in monomeric, trimeric, or ferritin-based nanoparticle forms.

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Background: SARS-CoV-2 transmission and COVID-19 disease severity is influenced by immunity from natural infection and/or vaccination. Population-level immunity is complicated by the emergence of viral variants. Antibody Fc-dependent effector functions are as important mediators in immunity.

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Lipid nanoparticle mRNA vaccines are an exciting but emerging technology used in humans. There is limited understanding of the factors that influence their biodistribution and immunogenicity. Antibodies to poly(ethylene glycol) (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination.

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Article Synopsis
  • A study investigated the timing of bivalent mRNA COVID-19 booster vaccinations in highly vaccinated adults, comparing immediate vs. a 3-month delayed administration.
  • The findings showed no significant difference in immune response (antibody levels and effectiveness against variants) between the two groups.
  • The results suggest that delaying booster shots does not provide any additional benefits in enhancing immunity during the current endemic phase of the virus.
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Objectives: Although antiretroviral therapy (ART) efficiently suppresses HIV viral load, immune dysregulation and dysfunction persist in people living with HIV (PLWH). γδ T cells are functionally impaired during untreated HIV infection, but the extent to which they are reconstituted upon ART is currently unclear.

Methods: Utilising a cohort of ART-treated PLWH, we assessed the frequency and phenotype, characterised functional responses and defined the impact of immune checkpoint marker expression on effector functions of both Vδ1 and Vδ2 T cells.

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Article Synopsis
  • - The emergency phase of the COVID-19 pandemic has ended, but ongoing research focuses on understanding the SARS-CoV-2 virus, its evolution, and the effects of infections.
  • - Studies are increasingly examining both acute and long-term impacts of COVID-19, including post-infection effects and potential therapies.
  • - An overview of current research efforts highlights advancements across clinical, epidemiological, and social areas to improve future pandemic response.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.

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Groundwater is one of the alternatives to surface water that can be used for drinking water; however, it normally exists with high iron and manganese content. In this study, a column study was conducted to observe the elimination of iron (Fe) and manganese (Mn) in the groundwater under different retention times by using zeolite immobilized with iron-oxidizing bacteria (IOB). Rossellomorea sp.

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Although the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infection in previously vaccinated individuals. Recall of spike-specific CD4 T cells was rapid, with cellular proliferation and extensive activation evident as early as 1 day post symptom onset.

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Vγ9Vδ2 T cells can recognize various molecules associated with cellular stress or transformation, providing a unique avenue for the treatment of cancers or infectious diseases. Nonetheless, Vγ9Vδ2 T-cell-based immunotherapies frequently achieve suboptimal efficacies in vivo. Enhancing the cytotoxic effector function of Vγ9Vδ2 T cells is one potential avenue through which the immunotherapeutic potential of this subset may be improved.

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Employing monoclonal antibodies to target vaccine antigens to different immune cells within lymph nodes where adaptive immunity is initiated can provide a mechanism to fine-tune the magnitude or the quality of immune responses. However, studying the effects of different targeting antibodies head-to-head is challenging due to the lack of a feasible method that allows rapid screening of multiple antibodies for their impact on immunogenicity. Here self-assembling ferritin nanoparticles are prepared that co-display vaccine antigens and the Fc-binding domain of Staphylococcal protein A, allowing rapid attachment of soluble antibodies to the nanoparticle surface.

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Objectives: Following infection with SARS-CoV-2, virus-specific antibodies are generated, which can both neutralise virions and clear infection via Fc effector functions. The importance of IgG antibodies for protection and control of SARS-CoV-2 has been extensively reported. By comparison, other antibody isotypes including IgA have been poorly characterised.

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Article Synopsis
  • Natural killer (NK) cells are crucial for the body's defense against viral infections, and their behavior can change based on past or current infections, particularly with viruses like HCMV and HIV-1.
  • In HIV-1-infected individuals, there is a notable increase in a specific NK cell type (CD57+NKG2C+), particularly when they are also infected with HCMV, and these cells remain prevalent even after patients undergo antiretroviral therapy.
  • These CD57+NKG2C+ NK cells are highly active and can effectively target and kill HIV-1-infected cells, indicating that they might contribute to HIV-1 disease progression or could be harnessed for therapeutic approaches.
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Background: The field of oncology is at the forefront of advances in artificial intelligence (AI) in health care, providing an opportunity to examine the early integration of these technologies in clinical research and patient care. Hope that AI will revolutionize health care delivery and improve clinical outcomes has been accompanied by concerns about the impact of these technologies on health equity.

Objective: We aimed to conduct a scoping review of the literature to address the question, "What are the current and potential impacts of AI technologies on health equity in oncology?"

Methods: Following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines for scoping reviews, we systematically searched MEDLINE and Embase electronic databases from January 2000 to August 2021 for records engaging with key concepts of AI, health equity, and oncology.

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Article Synopsis
  • - Researchers created a version of the human antibody IgG that binds to the SARS-CoV-2 receptor ACE2, forming an antiviral decoy that effectively neutralizes the virus across different strains.
  • - They found that various modifications to the Fc portion of the antibody influenced its ability to neutralize the virus and interact with immune system components, with some mutations enhancing neutralization while others boosted complement-dependent cytotoxicity.
  • - These findings highlight the potential to tailor Fc-based therapeutic agents for better protection against SARS-CoV-2 and potentially other viral infections by engineering specific immune responses.
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Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG, but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle-immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines or no SARS-CoV-2 vaccine for PEG-specific antibodies.

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Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4 T cell responses to the spike protein, including circulating follicular helper T (cT) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S tetramer to track spike-specific CD4 T cells, we show that primary infection or vaccination induces robust S-specific CXCR5 and cT cell memory responses. Secondary exposure induced recall of CD4 T cells with a transitory CXCR3 phenotype, and drove expansion of cT cells transiently expressing ICOS, CD38 and PD-1.

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Broadly neutralising antibodies (bNAbs) may play an important role in future strategies for HIV control. The development of anti-drug antibody (ADA) responses can reduce the efficacy of passively transferred bNAbs but the impact of ADA is imperfectly understood. We previously showed that therapeutic administration of the anti-HIV bNAb PGT121 (either WT or LALA version) controlled viraemia in pigtailed macaques with ongoing SHIV infection.

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Objectives: SARS-CoV-2 can be transmitted by aerosols, and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed the SARS-CoV-2-specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination.

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