Estimating SARS‐CoV‐2 Omicron XBB.1.5 Spike‐Directed Functional Antibody Levels From an Anti‐Receptor Binding Domain Wuhan‐Hu‐1‐Based Commercial Immunoassay Results DOI Creative Commons

Ángela Sánchez‐Simarro,

Enric Cuevas‐Ferrando, Daniel Fernández‐Soto

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(1)

Published: Jan. 1, 2025

ABSTRACT We investigated whether antibody concentrations measured in plasma using the Roche Elecsys® Anti‐SARS‐CoV‐2 S assay (targeting receptor binding domain, RBD) could estimate levels of Wuhan‐Hu‐1 and Omicron XBB.1.5 spike‐directed antibodies with neutralizing ability (NtAb) or those mediating NK‐cell activity. analyzed 135 samples from 39 vaccinated elderly nursing home residents. A strong correlation was found for NtAb against both (Rho = 0.73, p < 0.001) (sub)variants 0.001). Moderate positive correlations were observed activity, based on lysosome‐associated membrane protein 1 (LAMP1)‐producing NK cells stimulated 0.43, spike proteins 0.50, Similarly, interferon‐gamma (IFN‐γ)‐producing frequencies showed moderate (Wuhan‐Hu‐1: Rho 0.001; XBB.1.5: Random Forest models accurately predicted ( R 2 0.72), though less robust. Anti‐RBD 4.73 5.02 log 10 BAU/mL high XBB.1.5, respectively. Antibody thresholds predicting functional cell‐mediated responses 4.54 For LAMP1‐producing cells, 4.94 4.75 In summary, total anti‐RBD by may allow inference and, to a lesser extent, Fc‐mediated XBB.1.5.

Language: Английский

Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates DOI Creative Commons
Matthew Gagné, Barbara J. Flynn, Shayne F. Andrew

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(10), P. 1913 - 1927

Published: Sept. 3, 2024

Abstract A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 BA.5 spike proteins or a WA1–BA.5 chimpanzee adenoviral-vectored vaccine delivered by intranasal aerosol device. NHPs boosted either had minimal virus nose lungs, respectively. By contrast, was limited to lower airways. The mucosally elicited durable airway IgG IgA responses and, unlike vaccine, induced spike-specific B cells lungs. IgG, T cell correlated whereas alone upper protection. This study highlights differential serum correlates how vaccines can durably SARS-CoV-2.

Language: Английский

Citations

8
The hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies DOI Creative Commons
Arman Izadi, Yasaman Karami, Eleni Bratanis

et al.

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

Published: April 27, 2024

Abstract Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, engineer IgG2-4 subclasses of Ab25. Despite having reduced binding, IgG3 version promotes stronger phagocytosis bacteria. Using atomic simulations, show that IgG3’s Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions immune cells. We replaced four different IgG3-hinge segment subclasses, IgGh xx . Hinge-engineering does not diminish binding as but enhances function, where a 47 amino acid is comparable function. shows improved protection against S. systemic infection mouse model, suggesting promise preclinical therapeutic candidate. Importantly, enhanced function generalizable diverse strains from clinical isolates. versions anti-SARS-CoV-2 mAbs broaden biological applicability, and these also exhibit strongly compared subclass. The subclass two distant systems provides new insights into antibody

Language: Английский

Citations

6
Anti‐TNF therapy impairs both short‐ and long‐term IgG responses after repeated vaccination DOI Creative Commons

Jana Sophia Buhre,

Tamás Pongrácz, Ulf Geisen

et al.

Allergy, Journal Year: 2024, Volume and Issue: 80(2), P. 423 - 439

Published: July 25, 2024

Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects TNF blockade on short- long-term after repeated remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated sialylated Fc glycans, whilst Abs low levels galactosylation sialylation are most likely generated by long-lived plasma cells (PCs) derived primarily from germinal center (GC) response. Thus, glycosylation patterns may be applicable distinguish vaccine influence anti-TNF treatment. We used COVID-19 as a model investigate subclass patterns, B cell subsets, effector functions Ab up three vaccinations in or other immunosuppressive treatments healthy individuals. Using TriNetX, global healthcare database, we determined risk SARS-CoV-2 infections vaccinated treated drugs. Anti-TNF reduced abundance all anti-S subclasses sialylation. Re-activation potential memory initially antibodies, which were progressively each booster dose anti-TNF-treated patients, especially elderly. The (1) correlated diminished functional activity an increased for development COVID-19. data suggest reduces both GC-dependent PCs cell-derived short-lived PCs, hence long- responses, respectively, vaccination. propose therapy, elderly, benefit

Language: Английский

Citations

6
Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus DOI Creative Commons
Jacob A. Dillard, Sharon Taft-Benz, Audrey C. Knight

et al.

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

Published: May 3, 2024

Abstract Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these are protective against homologous coronavirus infection, emergence of novel variants and presence large zoonotic reservoirs harboring heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises risk adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model disease evaluate performance either challenge or bat-derived that represents potential emerging threat. We show can cause during while an alternative adjuvant does not drive promotes viral clearance. In this work, highlight impact selection on safety efficacy infection.

Language: Английский

Citations

5
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

5
Vaccine development against tuberculosis before and after Covid-19 DOI Creative Commons
Stefan H. E. Kaufmann

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 15, 2023

Coronavirus disease (Covid-19) has not only shaped awareness of the impact infectious diseases on global health. It also provided instructive lessons for better prevention strategies against new and current major importance. Tuberculosis (TB) is a health threat caused by

Language: Английский

Citations

12
Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants DOI Creative Commons
Ebene R. Haycroft, Samantha K. Davis, Pradhipa Ramanathan

et al.

Medical Microbiology and Immunology, Journal Year: 2023, Volume and Issue: 212(4), P. 291 - 305

Published: July 21, 2023

Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge worldwide public health. The receptor-binding domain (RBD) is hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated impact of RBD including 5 variants concern (VOC) or interest-including Omicron (BA.2)-and 33 common point both on IgG recognition and ACE2-binding inhibition, as well FcγRIIa- FcγRIIIa-binding antibodies, in plasma from two-dose BNT162b2-vaccine recipients mild-COVID-19 convalescent subjects obtained first wave using custom-designed bead-based 39-plex array. IgG-recognition FcγR-binding antibodies were decreased against Beta mutation G446S, found several sub-variants compared wild type. Notably, while there was profound decrease inhibition less affected, suggesting that Fc functional antibody responses may be better retained comparison neutralization. Furthermore, measurement RBD-ACE2-binding affinity via biolayer interferometry showed all VOC RBDs have enhanced human ACE2, demonstrate polymorphisms, E35K (rs1348114695) has reduced VOCs, K26R (rs4646116) S19P (rs73635825) increased binding kinetics potentially affecting virus-host interaction and, thereby, host susceptibility. Collectively, our findings provide in-depth coverage mutations key facets host-virus interactions.

Language: Английский

Citations

11
An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission DOI Creative Commons
Weizhong Li, Tao Wang, Arunraj Mekhemadhom Rajendrakumar

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 6, 2023

SARS-CoV-2 is primarily transmitted through droplets and airborne aerosols, in order to prevent infection reduce viral spread vaccines should elicit protective immunity the airways. The neonatal Fc receptor (FcRn) transfers IgG across epithelial barriers can enhance mucosal delivery of antigens. Here we explore FcRn-mediated respiratory spike (S). A monomeric was fused a stabilized spike; resulting S-Fc bound S-specific antibodies FcRn. Intranasal immunization mice with CpG significantly induced antibody responses compared vaccination S alone or PBS. Furthermore, intranasally immunized hamsters S-Fc. significant reduction virus replication nasal turbinate, lung, brain observed following challenges its variants. also reduced transmission hamsters. Nasal IgA, neutralizing antibodies, lung-resident memory T cells, bone-marrow plasma cells mediated protection. Hence, FcRn delivers an antigen effectively into airway induces protection against transmission.

Language: Английский

Citations

11
Therapeutic antibodies and alternative formats against SARS-CoV-2 DOI Creative Commons
Rahel R. Winiger, Laurent Perez

Antiviral Research, Journal Year: 2024, Volume and Issue: 223, P. 105820 - 105820

Published: Feb. 1, 2024

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) heavily burdened the entire world. Despite a prompt generation of vaccines and therapeutics to confront infection, virus remains threat. ancestor viral strain has evolved into several variants concern, with Omicron variant now having many distinct sublineages. Consequently, most available antibodies targeting spike went obsolete thus new therapies or therapeutic formats are needed. In this review we focus on antibody targets, provide an overview progress made so far, describe novel being explored, lessons learned from that can enhance preparedness.

Language: Английский

Citations

4
Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses DOI Creative Commons

Susanna E Barouch,

Taras M. Chicz, Ross Blanc

et al.

Open Forum Infectious Diseases, Journal Year: 2024, Volume and Issue: 11(4)

Published: March 13, 2024

Abstract Background The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, immunogenicity of concurrent vs separate administration these vaccines remains unclear. Methods Here, we analyzed antibody responses health care workers who received booster vaccine on same day or different days through systems serology. Antibody-binding functional characterized at peak after 6 months following vaccination. Results IgG1 neutralization to SARS-CoV-2 XBB.1.5 higher as compared with vaccines. While similar results not observed for responses, no interference was noted administration. Conclusions These data suggest that may yield more durable neutralizing while maintaining against influenza.

Language: Английский

Citations

4