A Cell-Based Systems Biology Assessment of Human Blood to Monitor Immune Responses after Influenza Vaccination

AbstractThe coronavirus disease of 2019 (COVID-19) has caused a global pandemic and led to nearly three million deaths globally. As of April 2021, there are still many countries that do not have COVID-19 vaccines. Before the COVID-19 vaccines were developed, some evidence suggested that an influenza vaccine may stimulate nonspecific immune responses that reduce the risk of COVID-19 infection or the severity of COVID-19 illness after infection. This study evaluated the association between influenza vaccination and the risk of COVID-19 infection. We conducted a retrospective cross-sectional study with data from July 1, 2019, to June 30, 2020 with the Claims data from Symphony Health database. The study population was adults age 65 years old or older who received influenza vaccination between September 1 and December 31 of 2019. The main outcomes and measures were odds of COVID-19 infection and severe COVID-19 illness after January 15, 2020. We found the adjusted odds ratio (aOR) of COVID-19 infection risk between the influenza-vaccination group and no-influenza-vaccination group was 0.76 (95% confidence interval (CI), 0.75–0.77). Among COVID-19 patients, the aOR of developing severe COVID-19 illness was 0.72 (95% CI, 0.68–0.76) between the influenza-vaccination group and the no-influenza-vaccination group. When the influenza-vaccination group and the other-vaccination group were compared, the aOR of COVID-19 infection was 0.95 (95% CI, 0.93–0.97), and the aOR of developing a severe COVID-19 illness was 0.95 (95% CI, 0.80–1.13). The influenza vaccine may marginally protect people from COVID-19 infection.

Download Full-text

Estimation of digestible sulphur amino acids requirements for growth performance and immune responses to Newcastle disease and avian influenza vaccination in broilers

Italian Journal of Animal Science ◽

10.1080/1828051x.2021.1938716 ◽

2021 ◽

Vol 20 (1) ◽

pp. 1002-1014

Author(s):

Saeed Ghavi ◽

Heydar Zarghi ◽

Abolghasem Golian

Keyword(s):

Amino Acids ◽

Avian Influenza ◽

Immune Responses ◽

Influenza Vaccination ◽

Growth Performance ◽

Newcastle Disease ◽

Sulphur Amino Acids

Download Full-text

Understanding Cell Interactions Using Modular Nanoparticle Libraries

Australian Journal of Chemistry ◽

10.1071/ch19269 ◽

2019 ◽

Vol 72 (8) ◽

pp. 595 ◽

Cited By ~ 1

Author(s):

Georgina K. Such ◽

Angus P. R. Johnston

Keyword(s):

Immune Responses ◽

Small Molecules ◽

Active Form ◽

Reticuloendothelial System ◽

Endosomal Escape ◽

Biological Interactions ◽

Nanoparticle Delivery ◽

A Cell ◽

Nanoparticle Structure ◽

The Right

Nanoparticle delivery systems have significant potential to facilitate the delivery of novel therapeutics, such as proteins, DNA or small molecules. However, there are multiple biological barriers that need to be overcome to deliver the cargo in an active form. These challenges include evading clearance by the reticuloendothelial system, minimising adverse immune responses, targeting specific cells and tissues, and trafficking into the right compartment of the cell. In this account, we will discuss how nanoparticle structure can be tuned to optimise biological interactions and thus improve the ability of nanoparticles to overcome these barriers. The focus of this article will be on controlling cell targeting and trafficking within a cell, e.g. endosomal escape.

Download Full-text

No cell is an island: circulating T cell:monocyte complexes are markers of immune perturbations

10.1101/411553 ◽

2018 ◽

Author(s):

Julie G. Burel ◽

Mikhail Pomaznoy ◽

Cecilia S. Lindestam Arlehamn ◽

Daniela Weiskopf ◽

Ricardo da Silva Antunes ◽

...

Keyword(s):

Flow Cytometry ◽

T Cell ◽

Immune Responses ◽

Human Blood ◽

Significant Proportion ◽

Complex Frequency ◽

The Common ◽

First Time ◽

High Resolution Microscopy

AbstractOur results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artefacts and thus ignored in data acquisition and analysis, are the result of true biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell:monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be revisited.

Download Full-text

A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans

Frontiers in Immunology ◽

10.3389/fimmu.2021.647873 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lynda Mottram ◽

Anna Lundgren ◽

Ann-Mari Svennerholm ◽

Susannah Leach

Keyword(s):

Systems Biology ◽

Immune Responses ◽

B Cell ◽

Vaccine Development ◽

Oral Vaccine ◽

Antibody Responses ◽

Cell Maturation ◽

Antigen Specificity ◽

B Cell Maturation ◽

B Cell Maturation Antigen

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

Download Full-text

SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

10.1101/2021.03.10.21253299 ◽

2021 ◽

Author(s):

Raymond T. Suhandynata ◽

Nicholas J. Bevins ◽

Jenny T. Tran ◽

Deli Huang ◽

Melissa A. Hoffman ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Adaptive Immune Response ◽

Antibody Assay ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Previous Infection ◽

A Cell

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

Download Full-text