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

Enhancing the therapeutic activity of hyperimmune IgG against chikungunya virus using FcγRIIIa affinity chromatography DOI Creative Commons
Julie M. Fox, Vicky Roy, Bronwyn M. Gunn

et al.

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

Published: May 12, 2023

Introduction Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease infection in animals. However, the ability improve therapeutic activity CHIKV-specific polyclonal IgG by enhancing through modulation subclass glycoforms remains unknown. Here, we evaluated protective efficacy CHIKV-immune enriched for binding Fc-gamma receptor IIIa (FcγRIIIa) select with enhanced Fc effector functions. Methods Total was isolated from convalescent donors without additional purification FcγRIIIa affinity chromatography. The characterized biophysical biological assays assessed during mice. Results FcγRIIIa-column afucosylated glycoforms. In vitro characterization showed had human mouse FcγRIV FcγR-mediated function reducing neutralization cellular assays. When administered as post-exposure therapy mice, promoted reduction viral load. Discussion Our study provides evidence that, increasing engagement FcγRs on cells, leveraging FcγRIIIa-affinity chromatography, antiviral reveals path produce more effective therapeutics against these potentially other emerging viruses.

Language: Английский

Citations

4
Sarbecovirus disease susceptibility is conserved across viral and host models DOI Creative Commons
Sarah R. Leist,

Alexandra Schäfer,

Ellen L Risemberg

et al.

Virus Research, Journal Year: 2024, Volume and Issue: 346, P. 199399 - 199399

Published: June 14, 2024

Coronaviruses have caused three severe epidemics since the start of 21

Language: Английский

Citations

1
Compartment-specific antibody correlates of protection to SARS-CoV-2 Omicron in macaques DOI Creative Commons
Xin Tong, Qixin Wang, Wonyeong Jung

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(9), P. 110174 - 110174

Published: June 5, 2024

Antibodies represent a primary mediator of protection against respiratory viruses. Serum neutralizing antibodies (NAbs) are often considered correlate protection. However, detailed antibody profiles including characterization functions in different anatomic compartments poorly understood. Here we show that correlates severe acute syndrome coronavirus 2 (SARS-CoV-2) challenge systemic versus mucosal rhesus macaques. In serum, NAbs were the strongest and linked to spike-specific binding other extra-NAb create larger protective network. bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved rather than NAbs. Within BAL, ADCP was immunoglobulin (Ig)G, IgA/secretory IgA, Fcγ-receptor antibodies. Our results support model which with mediate at sites.

Language: Английский

Citations

1
A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice DOI Creative Commons
James Brett Case,

Shilpa Sanapala,

Carly Dillen

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

1
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

Citations

3