bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.09.05.506626

Immune dynamics at single cell protein level after delta/omicron infection in COVID-19 vaccinated convalescent individuals

Abstract

Both COVID-19 mRNA or recombinant Adenovirus vector (rAdVV) based vaccines have shown a great efficacy in generating humoral and cellular immune responses. Two doses of the COVID-19 vaccines generate enough antibodies and generate spike-specific T cell responses. However, after 6-8 months there is a decline in antibody production and T cell responses. Due to the rise of new SARS-CoV-2 variants of concern, a third or even fourth dose of vaccine was recommended for the elderly, immune comprised and frontline medical health care workers. However, despite additional booster doses given, those who were infected with either delta or omicron (during December 2021 - March 2022) had symptoms of illness. By what means these COVID-19 vaccines provide immunity against the SARS-CoV-2 virus at the molecular level is not explored extensively yet and, it is an emerging research field as to how the SARS-CoV-2 virus is able to evade the host immunity. Most of the infected people had mild symptoms whilst some were asymptomatic. Many of the people had developed nucleocapsid antibodies against the SARS-CoV-2 delta/omicron variants confirming a humoral immune response against viral infection. Furthermore, cellular analysis shows that post-vaccinated recovered COVID-19 individuals have significantly reduced NK cells and increased T naive CD4+, TEM CD8+ and B cells. This decrease in cellular immunity corresponds to individuals who recovered from alpha variants infection and had mild symptoms. Our results highlight that booster doses clearly reduce the severity of infection against delta/omicron infection. Furthermore, our cellular and humoral immune system is trained by vaccines and ready to deal with breakthrough infections in the future.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bajaj, R., Yang, Z., Hammer, V., Poeschel, S., Beiber, K., Salker, M. S., Casadei, N., Ossowski, S., Riess, O., Singh, Y.. 2022-09-06. Immune dynamics at single cell protein level after delta/omicron infection in COVID-19 vaccinated convalescent individuals. https://doi.org/10.1101/2022.09.05.506626

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

ATF3 Preserves Macrophage Cholesterol Homeostasis during Metabolic Stress

Background: Macrophages must coordinate immune activation with maintenance of cellular cholesterol homeostasis, yet the transcriptional mechanisms integrating these processes remain incompletely understood. Activating transcription factor 3 (ATF3) suppresses inflammatory and interferon responses and has been implicated in macrophage lipid metabolism, suggesting a role in coordinating immune and sterol-responsive transcriptional programs. Methods: Wild-type and ATF3-deficient bone marrow-derived macrophages were analyzed by bulk RNA sequencing following Toll-like receptor stimulation and under conditions of sterol loading or depletion. Cholesterol content, cytokine production, and sterol-responsive gene expression were quantified. Human metabolic dysfunction-associated steatotic liver disease (MASLD) datasets and Kupffer cell-specific ATF3 knockout mice were used to assess disease relevance in vivo. Results: ATF3 deficiency enhanced inflammatory and interferon-responsive transcriptional programs while suppressing a sterol-responsive gene module enriched for SREBP2 target genes. This phenotype was conserved across diverse Toll-like receptor stimuli and accompanied by persistent Ch25h upregulation. Despite exhibiting elevated cellular cholesterol, ATF3-deficient macrophages retained transcriptional responsiveness to sterol loading and depletion while demonstrating reduced induction of SREBP2-dependent genes across conditions. IFNAR blockade reduced interferon-responsive gene expression but did not normalize Ch25h or sterol-responsive gene expression. In contrast, CRISPR-mediated reduction of Ch25h partially restored sterol-responsive gene expression in inflammatory ATF3-deficient macrophages. In human MASLD, hepatic ATF3 expression positively correlated with disease severity. In mice, ATF3 was preferentially induced in Kupffer cells during metabolic stress, and Kupffer cell-specific deletion of ATF3 increased liver injury and Kupffer cell lipid accumulation. Conclusions: ATF3 supports sterol-responsive transcriptional programs while restraining inflammatory activation in macrophages. ATF3 loss results in elevated cellular cholesterol, impaired SREBP2-dependent gene expression, and persistent derepression of Ch25h, which contributes to but does not fully explain the sterol phenotype. These findings identify ATF3 as a coordinator of macrophage adaptation to inflammatory and metabolic stress and support a protective role for Kupffer cell ATF3 during metabolic liver disease.

immunology↗

Therapeutic anti-IgE antibodies generate distinct functional immune complex signatures

Therapeutic IgG anti-IgE antibodies are benchmarked by their ability to interfere with IgE-Fc[epsilon]RI binding, but their activity within IgE and IgG-containing immune complexes remains poorly defined. Here we show that omalizumab and ligelizumab form binary IgE-IgG and ternary allergen-containing immune complexes with distinct functional properties. In primary human leukocytes, these complexes exhibited antibody- and composition-dependent patterns of cellular association and activation. Using multiplexed focal molography, we resolved Fc receptor engagement across free and complexed antibody states and identified distinct receptor-binding signatures for omalizumab- and ligelizumab-containing complexes. Notably, allergen incorporation reversed the relative ability of the two antibodies to neutralize IgE-Fc[epsilon]RI interactions and remodelled Fc[gamma]R binding. Thus, immune-complex composition is a determinant of therapeutic antibody function.

immunology↗

Proliferation and mutation as humoral immune response

The affinity maturation process, through which antibodies acquire relatively high affinity for an invading pathogen, involves complex mechanisms whose relative importance is not yet fully understood. This study proposes an analytical model of this process, to investigate the main factors governing proliferation and mutation and assess their respective roles. The model suggests that the immune system should not be expected to follow a single, rigid evolutionary pattern, as a wide range of proliferation and mutation strategies can yield nearly optimal outcomes. Keywords: Antibody, antigen, affinity, B-cell, mutation, proliferation

immunology↗