What type of vaccine immunity controls breakthrough COVID? DOI Creative Commons
Stephen J. Kent, Miles P. Davenport

Vaccine Insights, Journal Year: 2023, Volume and Issue: 02(08), P. 317 - 321

Published: Aug. 23, 2023

VIEWPOINT "There is interest in the possibility of developing mucosally targeted vaccines hope these may increase mucosal antibody levels, improve protection and reduce shedding virus..."

Language: Английский

Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin DOI Creative Commons
Jernej Pušnik,

Jasmin Zorn,

Werner O. Monzon-Posadas

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 10, 2024

Several studies have suggested the imprinting of SARS-CoV-2 immunity by original immune challenge without addressing formation de novo response to successive antigen exposures. As this is crucial for development antigenic sin, we assessed against mutated epitopes omicron after vaccine breakthrough. Our data demonstrate a robust humoral in thrice-vaccinated individuals following breakthrough which recall vaccine-induced memory. The and memory B cell responses altered regions surface proteins are impaired. T spike protein present due high cross-reactivity cells rather than response. findings, therefore, underpin speculation that vaccination may lead sin if future variants overcome immunity.

Language: Английский

Citations

10

Blood Distribution of SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine in Humans DOI Creative Commons
Stephen J. Kent, Shiyao Li, Thakshila Amarasena

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

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 on surface lipid nanoparticle, detectable humans boosted by human vaccination. We hypothesized PEG-specific antibodies could increase clearance vaccines. To test this, we developed methods quantify both vaccine ionizable frequent serial blood samples from 19 subjects receiving Moderna SPIKEVAX booster immunization. Both peaked 1-2 days post vaccination (median peak level 0.19 3.22 ng mL

Language: Английский

Citations

8

Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections DOI Creative Commons
Kevin J. Selva, Pradhipa Ramanathan, Ebene R. Haycroft

et al.

JCI Insight, Journal Year: 2023, Volume and Issue: 8(18)

Published: Sept. 21, 2023

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired and plasma antibodies COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19-recovered (recovered, vaccinated), individuals with breakthrough Delta or Omicron BA.2 infections infected). Saliva displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, IgA levels compared COVID-19-uninfected vaccinees. Furthermore, repeated mRNA boosted SARS-CoV-2-specific IgG2 IgG4 in both mucosa biofluids (saliva tears) plasma; however, these rises negatively correlated FcγR engagement plasma. IgG but not IgA, variants were dampened narrowed by increased preexisting vaccine-induced immunity the ancestral strain. Salivary delayed initiation following infection, BA.2, rose rapidly thereafter. Importantly, salivary engagements enhanced infections. Our data highlight how shapes has implications long-term protection COVID-19.

Language: Английский

Citations

11

Dynamic Profiling and Prediction of Antibody Response to SARS-CoV-2 Booster-Inactivated Vaccines by Microsample-Driven Biosensor and Machine Learning DOI Creative Commons
Sumin Bian, Min Shang, Ying Tao

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(4), P. 352 - 352

Published: March 25, 2024

Knowledge of the antibody response to third dose inactivated SARS-CoV-2 vaccines is crucial because it subject one largest global vaccination programs. This study integrated microsampling with optical biosensors profile neutralizing antibodies (NAbs) in fifteen vaccinated healthy donors, followed by application machine learning predict at given timepoints. Over a nine-month duration, and venipuncture were conducted seven individual A refined iteration fiber optic biolayer interferometry (FO-BLI) biosensor was designed, enabling rapid multiplexed biosensing NAbs both wild-type Omicron variants minutes. Findings revealed strong correlation (Pearson r 0.919, specificity 100%) between variant NAb levels microsamples sera. Following dose, sera increased 2.9-fold after days 3.3-fold within month, subsequently waning becoming undetectable three months. Considerable but incomplete evasion latest subvariants from booster vaccine-elicited confirmed, although higher number binding (BAbs) identified another FO-BLI Significantly, highly correlated pseudovirus neutralization assay identifying capacities 0.983). Additionally, demonstrated exceptional accuracy predicting levels, an error level <5% for BAbs across multiple Microsample-driven enables individuals access their results hours self-collection, while precise models could guide personalized strategies. The technology’s innate adaptability means has potential effective translation disease prevention vaccine development.

Language: Английский

Citations

4

SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire DOI Creative Commons
Alison Tarke,

Parham Ramezani-Rad,

Tertuliano Alves Pereira Neto

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(6), P. 101583 - 101583

Published: May 22, 2024

Little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS2) vaccine breakthrough infections (BTIs) on magnitude and breadth T cell repertoire after exposure to different variants. We studied samples from individuals who experienced symptomatic BTIs during Delta Omicron waves. In pre-BTI samples, 30% donors exhibited substantial immune memory against non-S (spike) SARS2 antigens, consistent with previous undiagnosed asymptomatic infections. Following BTI, we observed (1) enhanced S-specific CD4 CD8 responses in without infection, (2) expansion targets (M, N, nsps) independent variant, (3) generation novel epitopes recognizing variant-specific mutations. These accounted for 9%-15% total epitope repertoire. Overall, boost vaccine-induced by increasing broadening antigens recognized.

Language: Английский

Citations

4

Humoral and cellular immune responses following Omicron BA.2.2 breakthrough infection and Omicron BA.5 reinfection DOI Creative Commons

Xin‐Jing Zhao,

Bin Ji,

Chao Shang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(7), P. 110283 - 110283

Published: June 15, 2024

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy immunity induced by prior breakthrough infection (BTI) or reinfection against current circulating subvariants. Here, we prospectively investigated durability antibody and T cell responses in individuals post BA.2.2 BTI, with without subsequent BA.5 reinfection. Our findings reveal that emerging subvariants, including CH.1.1, XBB, JN.1, exhibit extensive immune evasion previous infections. Notably, level IgG neutralizing antibodies were found to correlate Fortunately, recognizing both BA.2 CH.1.1 peptides observed. Furthermore, may alleviate imprinting WT-vaccination, bolster virus-specific ICS

Language: Английский

Citations

4

Randomised controlled trial reveals no benefit to a 3-month delay in COVID-19 mRNA booster vaccine DOI Creative Commons
Wen Shi Lee, Jennifer Audsley, Mai-Chi Trieu

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(17)

Published: July 11, 2024

BACKGROUNDThere is uncertainty about the timing of booster vaccination against COVID-19 in highly vaccinated populations during present endemic phase COVID-19. Studies focused on primary have previously suggested improved immunity with a longer interval between first and second vaccine doses.METHODSWe conducted randomized, controlled trial (November 2022-August 2023) assigned 52 fully adults to an immediate or 3-month delayed bivalent Spikevax mRNA vaccine. Follow-up visits were completed for 48 participants (n = 24 per arm), collection saliva plasma samples following each visit.RESULTSThe rise neutralizing antibody responses ancestral Omicron strains almost identical arms. Analyses salivary (IgG, IgA), antibody-dependent phagocytic activity, decay kinetics similar 2 Symptomatic asymptomatic SARS-CoV-2 infections occurred 49% (21 49) over median 11.5 months follow-up also arms.CONCLUSIONSOur data suggest that there was no benefit delaying preimmune COVID-19.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry number 12622000411741 (https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12622000411741).FUNDINGNational Health Medical Research Council, Australia (program grant App1149990) Future Fund (App2005544).

Language: Английский

Citations

4

Randomised trial of same vs opposite arm co-administration of inactivated influenza and SARS-CoV-2 mRNA vaccines DOI Creative Commons
Wen Shi Lee, Kevin J. Selva, Jennifer Audsley

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

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

Language: Английский

Citations

0

Modulation of germinal center and antibody dynamics via ipsilateral versus contralateral immunization against SARS-CoV-2 DOI Creative Commons
Lauren Burmas, Wen Shi Lee, Andrew P. Kelly

et al.

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Abstract Human clinical trials have reported immunological outcomes can differ between ipsilateral (same side) and contralateral (alternate sides) prime-boost vaccination. However, our mechanistic understanding of how keeping or shifting the anatomical sites immunization impacts resultant germinal centers (GCs) antibody responses is limited. Here, we use an adjuvanted SARS-CoV-2 spike vaccine to dissect GC dynamics in draining lymph nodes serological following vaccination C57BL/6 mice. Contralateral elicited independent GCs at distinct nodes, where robust secondary only appeared upon distal vaccination, while ongoing from primary site were not boosted. In contrast, resulted sustained activity. Ipsilateral accelerated development titers against ancestral (wild-type [WT]), Beta, BA.1 but later comparable groups terms magnitude, durability, neutralization capacity beyond 28 d. Using a heterologous WT/BA.1 model, cross-reactive generated WT spike, with analogous homologous model. Within B cells, differential recognition antigens was observed further compartmentalized GCs, depending on regimes. Collectively, maintaining common augments kinetics memory cell recall transiently drive higher titers, longer-term are unaffected by localization immunization.

Language: Английский

Citations

0

Reading of Human Acute Immune Dynamics in Omicron SARS-CoV-2 Breakthrough Infection DOI Creative Commons

Haibo Li,

Hongyu Liu, Hongping Wu

et al.

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

The dynamics of the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections remain unclear, particularly when compared responses in naive individuals. In this longitudinal prospective cohort study, 13 participants were recruited. Peripheral blood samples collected every other day until 7 after symptom onset. Transcriptome sequencing, single-cell T-cell receptor (TCR) B-cell (BCR) Olink proteomics, and antigen-antibody binding experiments then performed. During incubation periods infections, peripheral exhibited type cytokine response, which shifted 1 upon Plasma levels C-X-C motif chemokine ligand 10, monocyte chemoattractant protein-1, interferon-γ, interleukin-6 show larger changes than naïve infections. inflammatory rapidly subsided, returning homeostasis by 5 Notably, monocyte-derived S100A8/A9, previously considered a marker disease, physiologically significantly increased early stages mild cases persisted 7, suggesting specific biological function. Longitudinal tracking also revealed that antibodies anti-Receptor Binding Domain (anti-RBD) onset, whereas cytotoxic T lymphocytes appeared 5. This study presents reference for interpreting immunological infectious disease humans.

Language: Английский

Citations

0