Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques DOI Creative Commons
Steven E. Bosinger, Christopher T Edwards, Kirti A. Karunakaran

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 30, 2024

The continued evolution of SARS-CoV-2 variants capable subverting vaccine and infection-induced immunity suggests the advantage a broadly protective against betacoronaviruses (beta-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from recovered-vaccinated donors neutralizing many other beta-CoVs. Many these mAbs target conserved S2 stem region spike protein, rather receptor binding domain contained within S1 primarily targeted by current vaccines. One S2-directed mAbs, CC40.8, has demonstrated efficacy in small animal models challenge. As next step pre-clinical testing as strategy to protect infection, we evaluated vivo CC40.8 clinically relevant non-human primate model conducting passive antibody transfer rhesus macaques (RM) followed mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n=6) RM, alongside one group that received control (PGT121). Viral loads lower airway were significantly reduced animals receiving higher doses CC40.8. We observed significant reduction inflammatory cytokines macrophages with 10mg/kg 1mg/kg genome sequencing lack escape mutations epitope. Collectively, data demonstrate efficiency S2-targeting infection while providing critical preclinical work necessary for development pan-beta-CoV

Language: Английский

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses DOI Open Access
Tonia L. Conner, Emilie Goguet, Hannah Haines-Hull

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 22, 2024

SUMMARY This study characterized antibody responses induced by COVID-19 mRNA vaccination and SARS-CoV-2 infection in saliva. Utilizing multiplex microsphere-based immunoassays, we measured saliva anti-SARS-CoV-2 spike IgG, IgA, secretory IgA 1,224 samples collected from healthcare workers the Prospective Assessment of Seroconversion between August 2020 through December 2022. By spring 2022, most individuals had detectable spike-specific antibodies Longitudinal measurements nucleocapsid IgG revealed that detected was driven subclinical clinically-evident infections, rather than alone. In contrast, strongly exhibited improved durability with hybrid immunity. Baseline levels to endemic human coronaviruses positively correlated post-vaccination levels. provides insights for development vaccines generate mucosal respiratory pathogens. HIGHLIGHTS Saliva anti-spike were present > 90% participants 2022 clinically evident infections alone a weak inducer HCoV immunity correlates post-vaccine

Language: Английский

Citations

2
Antibody response in elderly vaccinated four times with an mRNA anti-COVID-19 vaccine DOI Creative Commons
Alexander Rouvinski,

Ahuva Friedman,

Saveliy Kirillov

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 29, 2023

The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 II Quant assay) and neutralizing capacities (spike pseudovirus Wuhan Omicron BA.1 variant) were measured third doses among 46 residents (median age 85 years [IQR 81; 89]) an assisted living facility. Among participants never infected by SARS-CoV-2, mean serum RBD (2025 BAU/ml), 99 days vaccine, was as high 76 (1987 significantly higher (p = 0.030) when latter corrected for elapsed time. Neutralizing antibody historical strain (Mean 1046 vs 1573; p 0.002) broader (against Omicron) 170 375; 0.018), following vaccine. six individuals with breakthrough infection mounted strong immune responses antibodies variant indicating that did prevent specific adaptation response. These findings point out value continued boosting population.

Language: Английский

Citations

4
The SeroNet Clinical and Translational Serology Task Force (CTTF) SARS-CoV-2 mucosal immunity methodological considerations and best practices workshop DOI Creative Commons
Heidi Hempel, Nicholas J. Mantis, Christopher D. Heaney

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2023, Volume and Issue: 19(2)

Published: Aug. 1, 2023

SARS-CoV-2 persists in certain populations, even with vaccination and boosters. Emerging evidence suggests that reductions virus transmission infection will likely require involvement of the mucosal immune system, especially secretory antibodies upper respiratory tract. The Clinical Translational Serology Task Force (CTTF) within National Cancer Institute (NCI)'s Serological Sciences Network for COVID-19 (SeroNet) hosted a workshop to review status development standardization sample collection methods assays, identify challenges, develop action plans bridge gaps. Speakers presented data underscoring role IgA protection, markers as correlates tracking assessing antibodies, lessons learned from other infectious agents. Perspectives regulators industry were put forward guide vaccine development. Methodological considerations optimizing protocols assays harmonizing highlighted. Rigorous studies, standardized protocols, controls, standards, assay validation identified necessary gain momentum expanding vaccines mucosa.

Language: Английский

Citations

4
Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection DOI Creative Commons
Elena N. Atochina‐Vasserman, Lisa C. Lindesmith, Carmen Mirabelli

et al.

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

Published: Oct. 1, 2024

Language: Английский

Citations

1
A conserved N protein nano‐vaccine of COVID‐19 exerts potent and cross‐reactive humoral and cellular immune responses in mice DOI
Bing Li, Jing Zhang, Yang Huang

et al.

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(9)

Published: Sept. 1, 2023

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mutates continually, the current vaccines are unable to provide sufficient protection. It is important develop a broad-spectrum vaccine with conserved antigens prevent variant infection. Here we fused SARS-CoV-2 N protein Helicobacter pylori nonheme ferritin construct N-Ferritin nanoparticle vaccine. Compared monomer protein, nanoparticles induced more lymph node dendritic cells in mice trigger adoptive immunity. Following this, elicited robust and long-lasting antibody responses, which had better cross-reactivity SARS-CoV protein. also worth noting that higher levels of N-specific IgG IgA were distributed lungs N-Ferritin-immunized mice. Furthermore, resulted proportion interferon-γ+ CD8+ T cells, Tcm SARS-CoV-2, SARS-CoV, Middle East syndrome-related coronavirus. The N-based could promising developing strategy against variants other coronaviruses.

Language: Английский

Citations

3
Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques DOI Creative Commons
Steven E. Bosinger, Christopher T Edwards, Kirti A. Karunakaran

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 30, 2024

The continued evolution of SARS-CoV-2 variants capable subverting vaccine and infection-induced immunity suggests the advantage a broadly protective against betacoronaviruses (beta-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from recovered-vaccinated donors neutralizing many other beta-CoVs. Many these mAbs target conserved S2 stem region spike protein, rather receptor binding domain contained within S1 primarily targeted by current vaccines. One S2-directed mAbs, CC40.8, has demonstrated efficacy in small animal models challenge. As next step pre-clinical testing as strategy to protect infection, we evaluated vivo CC40.8 clinically relevant non-human primate model conducting passive antibody transfer rhesus macaques (RM) followed mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n=6) RM, alongside one group that received control (PGT121). Viral loads lower airway were significantly reduced animals receiving higher doses CC40.8. We observed significant reduction inflammatory cytokines macrophages with 10mg/kg 1mg/kg genome sequencing lack escape mutations epitope. Collectively, data demonstrate efficiency S2-targeting infection while providing critical preclinical work necessary for development pan-beta-CoV

Language: Английский

Citations

0