A Multivariant Surrogate Virus Neutralization Test Demonstrates Distinct SARS-CoV-2-Specific Antibody Responses in People Living with HIV after a Fourth Monovalent mRNA Vaccination or an Omicron Breakthrough Infection DOI Creative Commons
David Niklas Springer,

Simon Daller,

Michael Knappik

et al.

Diagnostics, Journal Year: 2024, Volume and Issue: 14(8), P. 822 - 822

Published: April 16, 2024

While neutralizing antibodies (nAbs) induced by monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are primarily directed against the wildtype (WT), subsequent exposure to Omicron variants may increase breadth of antibodies’ cross-neutralizing activity. Here, we analyzed impact an breakthrough infection (BTI) or a fourth mRNA vaccination on nAb profiles in people living with human immunodeficiency virus (PLWH). Using multivariant surrogate neutralization test (sVNT), quantified nAbs 36 three-times vaccinated PLWH, whom 9 acquired serologically confirmed BTI, 8 received vaccine dose, and 19 were neither infected nor additionally vaccinated. WT Delta increased after BTI vaccination, significant BA.1, BA.2, BA.5 was only observed BTI. However, there no difference concentrations between samples obtained vaccination. In contrast, levels significantly lower who three vaccinations. Thus, our study demonstrates suitability sVNT assess hybrid humoral immunity BTIs PLWH SARS-CoV-2.

Language: Английский

Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection DOI Creative Commons
H. J. Yang, Weiqi Hong, Lei Hong

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 19, 2023

Abstract The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants. In Chengdu, China, an infection wave was predominantly induced by BA.5 subvariant. It is crucial determine whether hybrid anti-SARS-CoV-2 immunity following infection, coupled with a variety immune background, sufficient shape responses against newly emerged subvariants, especially for XBB lineages. To investigate this, we collected serum nasal swab samples from 108 participants who had been infected this wave, evaluated neutralization pseudoviruses. Our results showed that convalescent sera individuals, regardless vaccination history, remarkably compromised capacities XBB.1.5 Although post-vaccination breakthrough slightly elevated plasma neutralizing antibodies part pseudoviruses, activities impaired Furthermore, analyzed impacts number vaccinations, age, sex on humoral cellular after infection. findings suggest lineages elicited current are remained at low levels, indicating urgent need development next-generation vaccines designed based sub-lineages other future variants.

Language: Английский

Citations

37

B-cell and antibody responses to SARS-CoV-2: infection, vaccination, and hybrid immunity DOI Creative Commons
Dennis Lapuente, Thomas Winkler, Matthias Tenbusch

et al.

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 144 - 158

Published: Nov. 10, 2023

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 prompted scientific, medical, and biotech communities to investigate infection- vaccine-induced immune responses the context this pathogen. B-cell antibody are at center these investigations, as neutralizing antibodies (nAbs) an important correlate protection (COP) from infection primary target SARS-CoV-2 vaccine modalities. In addition absolute levels, nAb longevity, neutralization breadth, immunoglobulin isotype subtype composition, presence mucosal sites have become topics for scientists health policy makers. recent pandemic was still is a unique setting which study de novo memory (MBC) dynamic interplay immunity. It also provided opportunity explore new platforms, such mRNA or adenoviral vector vaccines, unprecedented cohort sizes. Combined with technological advances years, situation has detailed mechanistic insights into development but revealed some unexpected findings. review, we summarize key findings last 2.5 years regarding immunity, believe significant value not only future vaccination approaches endemic settings.

Language: Английский

Citations

37

Bivalent COVID-19 mRNA booster vaccination (BA.1 or BA.4/BA.5) increases neutralization of matched Omicron variants DOI Creative Commons
David Niklas Springer, Michael Bauer, Iris Medits

et al.

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 4, 2023

Abstract We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose an original monovalent or bivalent BA.1- BA.4/BA.5-adapted vaccine had breakthrough infection with Omicron variants BA.1, BA.2 BA.4/BA.5. A BA.4/BA.5 Omicron-breakthrough induced increased Omicron-neutralization compared the booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or previous variants.

Language: Английский

Citations

27

Neutralization of SARS‐CoV‐2 Omicron XBB.1.5 and JN.1 variants after COVID‐19 booster‐vaccination and infection DOI Creative Commons
David Niklas Springer, Jeremy V. Camp,

Stephan W. Aberle

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(7)

Published: July 1, 2024

Abstract SARS‐CoV‐2 Omicron lineages continue to emerge and evolve into new sublineages, causing infection waves throughout 2022 2023, which has been attributed immune escape. We examined neutralizing antibody responses the recently emerged JN.1 variant in comparison ancestral D614G BA.1, BA.2, BA.5, XBB.1.5 variants. tested 79 human sera from cohorts with different combinations of vaccinations infections, including 23 individuals who had repeatedly exposed Omicron. Individuals a monovalent vaccine booster or breakthrough robust levels against all variants tested; however, evaded antibodies after single BA.2 BA.5 infections. Moreover, non‐vaccinated cohort, serum demonstrated almost no cross‐neutralization activities D614G, JN.1. infections earlier These findings show that SARS‐CoV‐2‐immunity is heterogeneous, depending on emphasize importance considering immune‐backgrounds when evaluating novel

Language: Английский

Citations

8

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages DOI Creative Commons
Young‐Jun Park, Dora Pinto, Alexandra C. Walls

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 10, 2022

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters result potent plasma neutralizing activity against BA.1 BA.2 breakthrough infections, but not vaccination-only, induce the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells of cases cross-react Wuhan-Hu-1, receptor-binding domains whereas primary infections elicit narrow specificity. While clinical have reduced neutralization Omicron, we identified ultrapotent pan-variant antibody, is unaffected any lineage a strong candidate for development.

Language: Английский

Citations

38

Reduced Sensitivity of Commercial Spike-Specific Antibody Assays after Primary Infection with the SARS-CoV-2 Omicron Variant DOI Creative Commons
David Niklas Springer, Thomas Perkmann,

Claudia Jani

et al.

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(5)

Published: Aug. 25, 2022

The SARS-CoV-2 Omicron variant is characterized by substantial changes in the antigenic structure of Spike (S) protein. Therefore, antibodies induced primary infection lack neutralizing activity against earlier variants. In this study, we analyzed whether these impact sensitivity commercial anti-SARS-CoV-2 antibody assays. Sera from 37 unvaccinated, convalescent individuals after putative were tested with a panel 20 immunoassays. As controls, used samples 43 ancestral wild-type strain. addition, variant-specific live-virus neutralization assays as reference for presence SARS-CoV-2-specific samples. Notably, convalescents, there was statistically significant reduction all containing S or its receptor-binding-domain (RBD) antigens. Furthermore, levels quantified displayed weaker correlation Omicron-specific titers than those wild type. contrast, nucleocapsid-protein-specific immunoassays similar and Omicron-infected subjects. summary, lead to reduced immunoreactivity current S- RBD-specific assays, impairing their diagnostic performance.

Language: Английский

Citations

30

Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies DOI Open Access
Pia Gattinger, Anna Ohradanova‐Repic, Rudolf Valenta

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5352 - 5352

Published: March 10, 2023

More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused unforeseen COVID-19 pandemic with millions of deaths. In meantime, SARS-CoV-2 has become endemic and is now part repertoire viruses causing seasonal severe respiratory infections. Due to several factors, among them development immunity through natural infection, vaccination current dominance seemingly less pathogenic strains belonging omicron lineage, situation stabilized. However, challenges remain possible new occurrence highly variants remains a threat. Here we review development, features importance assays measuring neutralizing antibodies (NAbs). particular focus on in vitro infection molecular interaction studying binding receptor domain (RBD) its cognate cellular ACE2. These assays, but not measurement SARS-CoV-2-specific per se, can inform us whether produced by convalescent or vaccinated subjects may protect against thus have potential predict risk becoming newly infected. This information extremely important given fact that considerable number subjects, vulnerable persons, respond poorly production antibodies. Furthermore, these allow determine evaluate virus-neutralizing capacity induced vaccines administration plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 synthetic compounds be used for therapy assist preclinical evaluation vaccines. Both types relatively quickly adapted emerging virus about magnitude cross-neutralization, which even estimate infected appearing variants. Given paramount discuss their specific features, advantages disadvantages, technical aspects yet fully resolved issues, such as cut-off levels predicting degree vivo protection.

Language: Английский

Citations

19

Immune interference in effectiveness of influenza and COVID-19 vaccination DOI Creative Commons
Yiwen Xie, Xuebin Tian, Xiaodi Zhang

et al.

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

Published: April 19, 2023

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely polio is almost extinct because of vaccines. Rabies vaccines Bacille Calmette-Guérin (BCG) could effectively protect humans against respective infections. However, both COVID-19 unable eliminate these two diseases their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) be negatively influenced (i.e., interfered with) by immune imprinting previous infections or vaccinations, repeated vaccinations interfere with VE due mismatch between vaccine strains endemic strains. Moreover, also when more than one kind administrated concomitantly co-administrated), suggesting that modulated vaccine-induced immunity. In this review, we revisit evidence support result from vaccine, interference co-administration types discussed. Regarding development next-generation vaccines, researchers should focus on induction cross-reactive T-cell responses naive B-cell overcome negative effects system itself. The strategy co-administrating needs considered carefully clinical data needed verify safe immunogenic.

Language: Английский

Citations

17

Safety and immunogenicity of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases compared with healthy controls DOI Open Access
Felix Kartnig, Daniel Mrak, Elisabeth Simader

et al.

Annals of the Rheumatic Diseases, Journal Year: 2022, Volume and Issue: 82(2), P. 292 - 300

Published: Sept. 15, 2022

Objectives A third COVID-19 vaccination is recommended for immunosuppressed patients. However, data on immunogenicity and safety of a in patients with immune-mediated inflammatory diseases (IMIDs) are sparse therefore addressed within this clinical trial. Methods 60 48 healthy controls (HCs) received an mRNA vaccine. The primary endpoint was defined as the presence antibody levels against receptor-binding domain (RBD)>1500 BAU/mL IMIDs versus HCs. Further endpoints included differences neutralising antibodies cellular immune responses after vaccination. Reactogenicity recorded 7 days, evaluated until week 4. Results Rate individuals anti-RBD antibodies>1500 not significantly different between HCs (91% vs 100% p=0.101). Anti-RBD were lower than (p=0.002 p=0.016, respectively). In contrast, fold increase 0 4 higher IMIDs. Treatment biological (b) disease-modifying anti-rheumatic drugs (DMARD) or combination bDMARDs conventional synthetic DMARDs associated reduced levels. Enhanced response to wild type Omicron peptide stimulation observed No serious adverse event attributed Conclusion Our trial support effects DMARD therapy should be considered. Trial registration number EudraCT No: 2021-002693-10.

Language: Английский

Citations

24

HLA Variation and SARS-CoV-2 Specific Antibody Response DOI Creative Commons
Dawit Wolday,

Chun Yiu Jordan Fung,

Gregory Morgan

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 906 - 906

Published: March 31, 2023

Differences in SARS-CoV-2-specific immune responses have been observed between individuals following natural infection or vaccination. In addition to already known factors, such as age, sex, COVID-19 severity, comorbidity, vaccination status, hybrid immunity, and duration of infection, inter-individual variations SARS-CoV-2 may, part, be explained by structural differences brought about genetic variation the human leukocyte antigen (HLA) molecules responsible for presentation antigens T effector cells. While dendritic cells present peptides with HLA class I CD8+ induce cytotoxic lymphocyte (CTLs), they II follicular helper B cell differentiation followed memory plasma maturation. Plasma then produce antibodies. Here, we review published data linking polymorphisms antibody responses. there is evidence that heterogeneity response might related variation, are conflicting findings due part study designs. We provide insight into why more research needed this area. Elucidating basis variability will help optimize diagnostic tools lead development new vaccines therapeutics against other infectious diseases.

Language: Английский

Citations

16