Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection
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ABSTRACT:
PROVIDER: PRJNA1089238 | ENA |
REPOSITORIES: ENA
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Project description:At this stage in the COVID-19 pandemic, most infections are 'breakthrough' infections that occur in individuals with prior immunity to SARS-CoV-2 through infection or vaccination. Understanding both innate and adaptive immune induction in the setting of breakthrough infection is critical to refining vaccine strategies to ensure long-term efficacy against emerging variants, yet existing studies have primarily focused on adaptive immune responses. Here, we performed single-cell transcriptomic, proteomic, and functional profiling of innate and adaptive immunity during primary and breakthrough COVID-19 infections by comparing immune responses between unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave. Breakthrough infections were characterized by a significantly less activated transcriptomic profile in CD56dim NK cells and monocytes, with induction of pathways limiting NK cell proliferation and monocyte migratory potential. Furthermore, we observed a female-specific trend of increased transcriptomic activation of CD16+ monocytes and type-2 conventional dendritic cells (cDC2s) during breakthrough infections. Despite these differences, antibody-dependent cellular cytotoxicity responses were similar between breakthrough and primary infection groups. These insights suggest that prior vaccination prevents overactivation of innate immune responses during breakthrough infections with discernible sex-specific patterns and underscore the potential of harnessing vaccines in mitigating pathologic immune responses resulting from overactivation.
2025-01-30 | GSE261862 | GEO
Project description:To gain a deeper understanding of Omicron waves in the context of vaccination, we performed scRNA-seq together with single-cell V(D)J sequencing using PBMCs from nine Omicron breakthrough infection patients and six vaccinees to identify the possible cellular and molecular response mechanisms after breakthrough infection.
2024-12-18 | GSE248556 | GEO
Project description:Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. Vaccine was dosed to induce binding antibody titers against ancestral spike, but not efficient virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post infection reflects both vaccination status and disease course, and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of neutralizing antibodies, correlates with recall of broadly reactive B- and T-cell responses.
2023-12-18 | GSE246866 | GEO
Project description:COVID-19 vaccination is associated with attenuation of inflammatory responses during breakthrough disease
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Project description:Prior vaccination exceeds prior infection in eliciting innate and humoral immune responses in Omicron infected outpatients
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Project description:Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.
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Project description:Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
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Project description:A greater understanding of the relationships between a vaccine, the immune response it induces, and protection from disease would greatly facilitate vaccine development. Modified Vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis (TB) vaccine designed to enhance responses induced by Bacille Calmette-Guerin (BCG). Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A and peaks one week post-vaccination, however, the variability in response between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression following vaccination with MVA85A and understand how these are related to long-term immunogenicity. 24 volunteers were vaccinated with 10^8 pfu MVA85A. 12 volunteers were vaccinated intramuscularly and 12 intradermally. Volunteers were healthy and did not have HIV, HCV, HBV or latent or active tuberculosis. Blood for this study was taken on the day of vaccination, immediately prior to the vaccine being given (day 0), and 2 and 7 days post-vaccination. Volunteers with a prior BCG vaccination were vaccinated with 1x10^8 pfu MVA85A either intradermally (id) or intramuscularly (im). Blood was taken immediately prior to vaccination (day 0) and 2 and 7 days post-vaccination. PBMCs were separated and frozen down. PBMCs were then thawed and RNA was extracted directly for microarray analysis. Some arrays contain control samples: from volunteers, incubated with either media alone or antigen 85, MVA85A or MVA wild type. These samples were used separately.
2012-09-28 | E-GEOD-40719 | biostudies-arrayexpress
Project description:Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood. Here we use systems immunology approaches, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences), to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean: 151 days after diagnosis) and 40 age- and sex-matched controls who never had COVID-19. At baseline and independent of time since COVID-19, recoverees had elevated T-cell activation signatures and lower expression of innate immune genes in monocytes. COVID-19-recovered males had coordinately higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy male and COVID-19-recovered females, partly because male recoverees had monocytes with higher IL-15 responses early after vaccination coupled with elevated pre-vaccination frequencies of "virtual memory" like CD8+ T-cells poised to produce more IFNg upon IL-15 stimulation. In addition, the expression of the repressed innate immune genes in monocytes increased by day 1 through day 28 post-vaccination in recoverees, thus moving towards the pre-vaccination baseline of healthy controls. In contrast, these genes decreased on day 1 and returned to the baseline by day 28 in controls. Our study reveals sex-dimorphic impacts of prior mild COVID-19 and suggests that viral infections in humans can establish new immunological set-points impacting future immune responses in an antigen-agnostic manner.
2022-03-09 | GSE194378 | GEO
Project description:Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood. Here we use systems immunology approaches, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences), to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean: 151 days after diagnosis) and 40 age- and sex-matched controls who never had COVID-19. At baseline and independent of time since COVID-19, recoverees had elevated T-cell activation signatures and lower expression of innate immune genes in monocytes. COVID-19-recovered males had coordinately higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy male and COVID-19-recovered females, partly because male recoverees had monocytes with higher IL-15 responses early after vaccination coupled with elevated pre-vaccination frequencies of "virtual memory" like CD8+ T-cells poised to produce more IFNg upon IL-15 stimulation. In addition, the expression of the repressed innate immune genes in monocytes increased by day 1 through day 28 post-vaccination in recoverees, thus moving towards the pre-vaccination baseline of healthy controls. In contrast, these genes decreased on day 1 and returned to the baseline by day 28 in controls. Our study reveals sex-dimorphic impacts of prior mild COVID-19 and suggests that viral infections in humans can establish new immunological set-points impacting future immune responses in an antigen-agnostic manner.
2023-01-04 | GSE206265 | GEO