Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus DOI Creative Commons
Jimin Lee, Samantha K. Zepeda, Young‐Jun Park

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 13, 2023

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with antigenicity their spike (S) glycoproteins remain uncharacterized. Here, we show that African Rinolophus bat sarbecovirus PRD-0038 S has a broad ACE2 usage and RBD mutations further expand promiscuity enable human utilization. We determined cryoEM structure bound to R. alcyone ACE2, explaining highlighting differences SARS-CoV-1 SARS-CoV-2. Characterization using monoclonal antibody reactivity revealed its distinct relative SARS-CoV-2 identified cross-neutralizing antibodies for pandemic preparedness. vaccination elicited greater titers cross-reacting vaccine-mismatched 2 1a sarbecoviruses compared due broader antigenic targeting, motivating inclusion antigens in next-generation vaccines enhanced resilience viral evolution.

Language: Английский

Systems Serology-Based Comparison of Humoral Immune Responses Induced by Liposome or Aluminum Hydroxide Adjuvanted SARS-CoV-2 Spike Protein DOI
Soo Ji Kim, Taewoo Kim,

Satyanarayana Bejjani

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Adjuvants play a crucial role in enhancing vaccine-induced immune responses by shaping the magnitude and quality of humoral cellular immunity. However, mechanism through which different adjuvants modulate effector functions is not fully understood. Here, we developed an International Vaccine Institute liposome-based adjuvant (ILA) comprehensively compared profiles mice following administration SARS-CoV-2 spike (S) protein formulated with either ILA or aluminum hydroxide (alum) using systems serology approach. No significant differences were observed antigen-specific total IgG neutralizing antibody titers between two adjuvanted groups. group demonstrated broader spectrum responses, exhibiting higher levels IgG2a, IgG2b, IgG3 to alum group. In addition, S-specific binding Fcγ receptor (FcγR) 1 FcγR4 was significantly alum. Moreover, Fc-mediated functions, such as antibody-mediated monocyte neutrophil phagocytosis, more active ILA-adjuvanted Overall, these findings demonstrate that induces antibodies superior FcγR alum, highlighting its potential improving

Language: Английский

Citations

0
Immunoglobulin replacement products confer in vivo protection against SARS-CoV-2 XBB.1.5 Omicron variant despite poor neutralizing activity DOI Creative Commons
Ofer Zimmerman,

Alexa Michelle Altman Doss,

Baoling Ying

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 4, 2024

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other dysregulation disorders, who have poor responses to vaccination require passive immunity conferred by commercial antibody products. The binding, neutralizing, protective activity of intravenously administered immunoglobulin against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG manufactured from December 2019 August 2022. We show that pre-pandemic had no appreciable cross-reactivity or neutralizing SARS-CoV-2. Anti-spike titers WA1/2020 D614G increased gradually after the pandemic started reached levels comparable vaccinated healthy donors 18 months diagnosis first COVID-19 case United States January 2020. average time between production infusion was 8 months, which resulted neutralization variant strain circulating at infusion. Despite limited activity, prophylaxis clinically relevant dosing protected susceptible K18-hACE2 transgenic mice clinical disease, lung infection, inflammation caused XBB.1.5 Omicron variant. Moreover, following prophylaxis, infection were higher FcγR KO than wild-type mice. Thus, evolving likely confer protection disorders through Fc-effector function mechanisms.

Language: Английский

Citations

3
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

3
Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice DOI Creative Commons
Elif Karaaslan, Teresa E. Sorvillo, Florine E. M. Scholte

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Abstract Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or the GP38 domain of GPC, can be protective when proteins are delivered viral vectors as a DNA RNA vaccine. Subunit vaccines safe and cost-effective alternative to some vaccine platforms, but Gc Gn subunit for CCHFV fail protect despite eliciting high levels neutralizing antibodies. Here, we investigated humoral cellular immune responses efficacy recombinant NP, GP38, forms (GP85 GP160) associated highly glycosylated mucin-like (MLD) domain, well NP + combination. Vaccination GP160, GP85, did not confer protection, vaccination MLD-associated blunted worsened clinical chemistry, increased in blood compared vaccination. In contrast, conferred 100% protection from lethal outcome was mild disease, while combination even more robust by reducing morbidity receiving alone. Thus, alone is promising candidate conferring survival against heterologous challenge. Moreover, incorporation should considered it further enhances surviving animals.

Language: Английский

Citations

3
Understanding Fc function for rational vaccine design against pathogens DOI Creative Commons
Kathryn Bowman, Paulina Kapłonek, Ryan P. McNamara

et al.

mBio, Journal Year: 2023, Volume and Issue: 15(1)

Published: Dec. 19, 2023

Antibodies represent the primary correlate of immunity following most clinically approved vaccines. However, their mechanisms action vary from pathogen to pathogen, ranging neutralization, opsonophagocytosis, cytotoxicity. Antibody functions are regulated both by antigen specificity (Fab domain) and interaction Fc domain with distinct types receptors (FcRs) present in immune cells. Increasing evidence highlights critical nature Fc:FcR interactions controlling spread limiting disease state. Moreover, variation Fc-receptor engagement during course infection has been demonstrated across a range pathogens, this can be further influenced prior exposure(s)/immunizations, age, pregnancy, underlying health conditions. functional occurs at level antibody isotype subclass selection as well post-translational modification antibodies that shape Fc:FcR-interactions. These factors collectively support model whereby system actively harnesses directs fight disease. By defining precise humoral control infections, understanding how these tuned, it may possible open new paths for improving existing or novel

Language: Английский

Citations

8
Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions DOI Creative Commons

C. Pierre,

Lily E. Adams, Kara Anasti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 26, 2023

ABSTRACT Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be yet it protected mice cynomolgus macaques from severe disease. The mechanisms of this antibody-mediated protection are unknown. Here we show Fc mediate (non-nAb) MA10 viral challenge in mice. Though non-nAb infusion did not suppress infectious titers lung as potently NTD (nAb) infusion, disease markers including gross discoloration were similar nAb groups. functional knockout substitutions abolished increased group. Finally, enhancement relative WT, supporting a positive association between functionality degree infection. This study demonstrates non-nAbs can utilize Fc-mediated lower load prevent damage due coronavirus AUTHOR SUMMARY COVID-19 has claimed over 6.8 million lives worldwide caused economic social disruption globally. Preventing more deaths is principal goal biologic vaccine developers. To guide design such countermeasures, an understanding how immune system prevents needed. We demonstrate here other than neutralization contribute Specifically, antibodies rely on its portion confer challenged with mouse adapted version SARS-CoV-2. Mice given could neutralize still showed decrease amount virus lungs less irrelevant antibody. even larger when engineered antibody-dependent cellular cytotoxicity potently. Thus, absence activity, binding overall defense infection progression.

Language: Английский

Citations

7
A Nasal Vaccine Candidate, Containing Three Antigenic Regions from SARS-CoV-2, to Induce a Broader Response DOI Creative Commons
Yadira Lobaina, Rong Chen, Edith Suzarte

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(6), P. 588 - 588

Published: May 28, 2024

A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli. The N fragment belongs to C-terminal domain whereas spans fibre structure post-fusion conformation spike protein. resultant named S2NDH, able form spherical particles 10 nm, which forms aggregates upon mixture with CpG ODN-39M. Both preparations were recognized positive COVID-19 human sera. S2NDH + ODN-39M formulation administered intranasal route resulted highly immunogenic Balb/c mice. It induced cross-reactive anti-N humoral immunity both sera bronchoalveolar fluids, under Th1 pattern. cell-mediated (CMI) also broad, response even against protein SARS-CoV-1. However, neither neutralizing antibodies (NAb) nor CMI region obtained. As alternative, RBD included inducer NAb. Upon evaluation mice route, clear adjuvant effect detected for preparation over RBD. High levels NAb SARS-CoV-2 bivalent RBD, constitutes an attractive proposal booster vaccine sarbecovirus scope.

Language: Английский

Citations

2
SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity DOI

Mario A. Peña-Hernández,

Mia Madel Alfajaro, Renata B. Filler

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(8), P. 2038 - 2050

Published: July 29, 2024

Language: Английский

Citations

2
Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families DOI Creative Commons
Matthew J. Vukovich, Andrea R. Shiakolas, Jared Lindenberger

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(9), P. e1012499 - e1012499

Published: Sept. 18, 2024

Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains a virus provide barrier to evolution escape mutants. Using LIBRA-seq (linking B cell receptor antigen specificity through sequencing) data the repertoire an individual chronically infected with human immunodeficiency type 1 (HIV-1), we identified lineage IgG3 predicted bind HIV-1 Envelope (Env) influenza A Hemagglutinin (HA). Two members, 2526 546, were confirmed large panel diverse antigens, including several Env, HA, coronavirus (CoV) spike, hepatitis C (HCV) E protein, Nipah (NiV) F Langya (LayV) protein. We found both complex glycans on antigenic surfaces. Antibody targets stem region HA N-terminal domain (NTD) SARS-CoV-2 spike. crystal structure Fab bound mannose revealed presence glycan-binding pocket light chain. cross-reacted from pathogens displayed no signs autoreactivity. These features distinguish previously described glycan-reactive antibodies. Further study this class may aid in selection engineering broadly therapeutics inform effective vaccines exceptional breadth pathogen coverage.

Language: Английский

Citations

2
Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV DOI Creative Commons
Naveenchandra Suryadevara, Nurgun Kose, Sandhya Bangaru

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 135(3)

Published: Nov. 26, 2024

The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target SARS-CoV-2 NTD potently neutralize virus. This finding suggests may contribute, part, to protective immunity. Pansarbecovirus are desirable for broad protection, but region SARS-CoV and exhibit a high level sequence divergence; therefore, cross-reactive NTD-specific unexpected, there no structure antibody complex with NTD. Here, we report monoclonal COV1-65, encoded by IGHV1-69 gene, recognizes S protein. A prophylaxis study showed mAb COV1-65 prevented disease when administered before challenge BALB/c mice, an effect requires intact fragment crystallizable (Fc) effector functions optimal protection vivo. footprint on near functional components S2 fusion machinery, selection escape mutant viruses identified critical residues Y886H Q974H, which likely affect epitope through allosteric effects. Structural features COV1-65-SARS-CoV antigen interaction suggest antigenic determinants should be considered rational design sarbecovirus vaccine candidates.

Language: Английский

Citations

2