scholarly journals Immune profiling reveals early disease trajectories associated with COVID-19 mortality: a sub-study from the ACTT-1 trial

2021 ◽  
Author(s):  
Joshua M Thiede ◽  
Abigail R Gress ◽  
Samuel D Libby ◽  
Christine E Ronayne ◽  
William E Matchett ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antiviral Therapy ◽  
Symptom Onset ◽  
Antibody Responses ◽  
Early Disease ◽  
Host Immune Responses ◽  
Study Enrollment ◽  
Cytokine Responses ◽  
Study Participants ◽  
Immune Profiling

Abstract COVID-19 outcomes are linked to host immune responses and may be impacted by antiviral therapy. We investigated antibody and cytokine responses in ACTT-1 study participants enrolled at our center. We studied serum specimens from 19 hospitalized adults with COVID-19 randomized to treatment with remdesivir or placebo. We assessed SARS-CoV-2 antibody responses and identified cytokine signatures using hierarchical clustering. We identified no clear immunologic trends attributable to remdesivir treatment. Seven subjects were initially seronegative at study enrollment, and all four deaths occurred in this group with more recent symptom onset. We identified three dominant cytokine signatures, demonstrating different disease trajectories.

scholarly journals Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shidan Tosif ◽  
Melanie R. Neeland ◽  
Philip Sutton ◽  
Paul V. Licciardi ◽  
Sohinee Sarkar ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Family Members ◽  
Antibody Responses ◽  
Healthy Controls ◽  
Serological Testing ◽  
Igg Antibody ◽  
Cytokine Responses ◽  
Asymptomatic Infections ◽  
Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

scholarly journals Acute and Chronic Phases of Toxoplasma gondii Infection in Mice Modulate the Host Immune Responses

1998 ◽  
Vol 66 (6) ◽  
pp. 2991-2995 ◽  
Author(s):  
T. D. Nguyen ◽  
G. Bigaignon ◽  
J. Van Broeck ◽  
M. Vercammen ◽  
T. N. Nguyen ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Soluble Protein ◽  
Chronic Phase ◽  
Antibody Responses ◽  
Protein Antigen ◽  
Host Immune Responses ◽  
Toxoplasma Gondii Infection ◽  
Igg1 Isotype ◽  
Murine Antibody

ABSTRACT Murine antibody responses to soluble proteins are generally restricted to the immunoglobulin G1 (IgG1) isotype. When mice were infected with Toxoplasma gondii Beverley and concomitantly immunized with a soluble unrelated protein antigen, a modification in the isotypic distribution of antibodies directed against this nonparasite antigen was observed, with a preferential production of IgG2a. Interestingly, when mice were immunized with a soluble protein antigen during the chronic phase (day 40) of infection with T. gondii Beverley, a similar modification in the isotypic distribution of antiprotein antibodies was observed.

scholarly journals Time of day of vaccination affects SARS-CoV-2 antibody responses in an observational study of healthcare workers

2021 ◽  
Author(s):  
Wei Wang ◽  
Peter Balfe ◽  
David W Eyre ◽  
Sheila F Lumley ◽  
Denise O'Donnell ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Time Of Day ◽  
Antibody Responses ◽  
Post Vaccination ◽  
Host Immune Responses ◽  
Vaccine Type ◽  
Multiple Pathogens ◽  
Vaccination Time

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time-of-day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, age, sex, and days post-vaccination on anti-Spike antibody responses in healthcare workers. The magnitude of the anti-Spike antibody response associated with the time-of-day of vaccination, vaccine type, participant age, sex, and days post vaccination. These results may be relevant for optimizing SARS-CoV-2 vaccine efficacy.

scholarly journals Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotoxemia versus ex vivo stimulation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dina M. Tawfik ◽  
Jacqueline M. Lankelma ◽  
Laurence Vachot ◽  
Elisabeth Cerrato ◽  
Alexandre Pachot ◽  
...  
Keyword(s):  
Immune Responses ◽  
Ex Vivo ◽  
Host Immune Responses ◽  
Immune Profiling

scholarly journals Efficient mucosal antibody response to SARS-CoV-2 vaccination is induced in previously infected individuals

2021 ◽  
Author(s):  
Kaori Sano ◽  
Disha Bhavsar ◽  
Gagandeep Singh ◽  
Daniel Floda ◽  
Komal Srivastava ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Mucosal Immunity ◽  
Respiratory Infections ◽  
Antibody Responses ◽  
Secretory Iga ◽  
Mucosal Antibody ◽  
Before And After ◽  
Paired Serum ◽  
Study Participants

AbstractMucosal immune responses are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. We analyzed, therefore, paired serum and saliva samples from study participants with and without COVID-19 at multiple timepoints before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. Our data indicate that vaccinated seropositive individuals were able to swiftly induce relatively high anti-spike SIgA responses by boosting pre-existing mucosal immunity. In contrast, seronegative individuals did not have pre-existing anti-SARS-CoV-2 or cross-reacting anti-HCoV SIgA antibodies prior to vaccination, and, thus, little or no anti-SARS-CoV-2 SIgA antibodies were induced by vaccination in these individuals.

scholarly journals Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

2020 ◽  
Author(s):  
Shidan Tosif ◽  
Melanie Neeland ◽  
Philip Sutton ◽  
Paul Licciardi ◽  
Sohinee Sarkar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Chronic Exposure ◽  
Family Members ◽  
Asymptomatic Infection ◽  
Antibody Responses ◽  
Healthy Controls ◽  
Serological Testing ◽  
Igg Antibody ◽  
Cytokine Responses ◽  
Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have mild or asymptomatic infection, but the underlying immunological differences remain unclear. We describe clinical features, virology, longitudinal cellular and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who were repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children were similar to their parents at all timepoints. All family members had salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincided with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child had IgG antibody detected against the S1 protein and virus neutralising activity ranging from just detectable to robust titers. Using a systems serology approach, we show that all family members demonstrated higher levels of SARS-CoV-2-specific antibody features than healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological evidence of infection. This raises the possibility that despite chronic exposure, immunity in children prevents establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may therefore not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

scholarly journals Systems immune profiling of variant-specific vaccination against SARS-CoV-2

2021 ◽  
Author(s):  
Lei Peng ◽  
Jonathan J. Park ◽  
Zhenhao Fang ◽  
Xiaoyu Zhou ◽  
Matthew B. Dong ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Immune Cell ◽  
Global Gene Expression ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Repertoire Diversity ◽  
Immune Profiling

AbstractLipid-nanoparticle(LNP)-mRNA vaccines offer protection against COVID-19. However, multiple variant lineages caused widespread breakthrough infections. There is no report on variant-specific vaccines to date. Here, we generated LNP-mRNAs specifically encoding wildtype, B.1.351 and B.1.617 SARS-CoV-2 spikes, and systematically studied their immune responses in animal models. All three LNP-mRNAs induced potent antibody responses in mice. However, WT-LNP-mRNA vaccination showed reduced neutralization against B.1.351 and B.1.617; and B.1.617-specific vaccination showed differential neutralization. All three vaccine candidates elicited antigen-specific CD8 and CD4 T cell responses. Single cell transcriptomics of B.1.351-LNP-mRNA and B.1.617-LNP-mRNA vaccinated animals revealed a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induced a systemic increase in reactive CD8 T cell population, with a strong signature of transcriptional and translational machineries in lymphocytes. BCR-seq and TCR-seq unveiled repertoire diversity and clonal expansions in vaccinated animals. These data provide direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.

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