Protective Non-neutralizing anti–N-terminal Domain mAb Maintains Fc-mediated Function against SARS-COV-2 Variants up to BA.2.86-JN.1 with Superfluous In Vivo Protection against JN.1 Due to Attenuated Virulence DOI

Arman Izadi,

Magdalena Godzwon, Anna Söderlund‐Strand

и другие.

The Journal of Immunology, Год журнала: 2024, Номер 213(5), С. 678 - 689

Опубликована: Июль 17, 2024

Substantial evidence supports that Fc-mediated effector functions of anti-spike Abs contribute to anti-SARS-Cov-2 protection. We have previously shown two non-neutralizing but opsonic mAbs targeting the receptor-binding domain and N-terminal (NTD), Ab81 Ab94, respectively, are protective against lethal Wuhan SARS-CoV-2 infection in K18-hACE2 mice. In this article, we investigated whether these maintain function Ag binding mutated variants. Ab94 retained their nanomolar affinity toward Omicron its subvariants, such as BA.2, BA.4, BA.5, XBB, XBB1.5, BQ1.1. However, when encountering more heavily BA.2.86, lost function, whereas 10 new mutations NTD did not affect Ab94. vivo experiments with mice inoculated a stringent dose 100,000 PFU JN.1 variant revealed unexpected results. Surprisingly, exhibited low disease manifestation animal model no weight loss or death control group. Still, assessment using clinical scoring system showed better protection for Ab94-treated mice, indicating still beneficial. Our work shows anti-receptor-binding mAb reactivity BA.2.86 emerged, anti-NTD was functional. Finally, adds insight into evolution virus by reporting is substantially less virulent than previous strains.

Язык: Английский

Prolonged SARS-CoV-2 Infection in Patients Receiving Anti-CD20 Monoclonal Antibodies: A Diagnostic Challenged by Negative Nasopharyngeal RT-PCR and Successful Treatment with COVID-19 High-Titer Convalescent Plasma DOI Creative Commons

Léa Da Silva,

Timothée Klopfenstein, Vincent Gendrin

и другие.

Viruses, Год журнала: 2023, Номер 15(11), С. 2220 - 2220

Опубликована: Ноя. 7, 2023

We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia four severely immunocompromised patients currently being treated anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative all patients. SARS-CoV-2 infection confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine convalescent plasma administered complete recovery

Язык: Английский

Процитировано

3
Combinatorial Regimens Augment Drug Monotherapy for SARS-CoV-2 Clearance in Mice DOI Open Access
Irfan Ullah, Fanny Escudié, Ivan Scandale

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 1, 2023

Summary Direct acting antivirals (DAAs) represent critical tools for combating SARS-CoV-2 variants of concern (VOCs) that evolve to escape spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging evaluate therapeutic efficacy DAAs target RNA-dependent RNA polymerase (favipiravir, molnupiravir) or Main protease (nirmatrelvir) against Delta Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best followed by molnupiravir favipiravir suppressing viral loads lung. Unlike neutralizing antibody treatment, DAA monotherapy did not eliminate However, targeting two enzymes combining nirmatrelvir resulted superior virus clearance. Furthermore, Caspase-1/4 inhibitor mitigated inflammation lung pathology whereas COVID-19 convalescent plasma yielded rapid clearance 100% survival. Thus, our study provides insights into treatment efficacies other effective combinations bolster arsenal.

Язык: Английский

Процитировано

2
Late Administration and Corticosteroid Usage Explain Inefficacy in COVID-19 Convalescent Plasma Trial DOI Open Access
Arturo Casadevall, David J. Sullivan

The Journal of Infectious Diseases, Год журнала: 2023, Номер 229(2), С. 617 - 618

Опубликована: Ноя. 15, 2023

Язык: Английский

Процитировано

2
IgG Subclass Switch in Volunteers Repeatedly Immunized with the Full-Length Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) DOI Creative Commons

Veronika Rathay,

Kristin Fürle,

Viktoria Kiehl

и другие.

Vaccines, Год журнала: 2024, Номер 12(2), С. 208 - 208

Опубликована: Фев. 17, 2024

Vaccines are highly effective tools against infectious diseases and also considered necessary in the fight malaria. Vaccine-induced immunity is frequently mediated by antibodies. We have recently conducted a first-in-human clinical trial featuring SumayaVac-1, malaria vaccine based on recombinant, full-length merozoite surface protein 1 (MSP1

Язык: Английский

Процитировано

0
Protective Non-neutralizing anti–N-terminal Domain mAb Maintains Fc-mediated Function against SARS-COV-2 Variants up to BA.2.86-JN.1 with Superfluous In Vivo Protection against JN.1 Due to Attenuated Virulence DOI

Arman Izadi,

Magdalena Godzwon, Anna Söderlund‐Strand

и другие.

The Journal of Immunology, Год журнала: 2024, Номер 213(5), С. 678 - 689

Опубликована: Июль 17, 2024

Substantial evidence supports that Fc-mediated effector functions of anti-spike Abs contribute to anti-SARS-Cov-2 protection. We have previously shown two non-neutralizing but opsonic mAbs targeting the receptor-binding domain and N-terminal (NTD), Ab81 Ab94, respectively, are protective against lethal Wuhan SARS-CoV-2 infection in K18-hACE2 mice. In this article, we investigated whether these maintain function Ag binding mutated variants. Ab94 retained their nanomolar affinity toward Omicron its subvariants, such as BA.2, BA.4, BA.5, XBB, XBB1.5, BQ1.1. However, when encountering more heavily BA.2.86, lost function, whereas 10 new mutations NTD did not affect Ab94. vivo experiments with mice inoculated a stringent dose 100,000 PFU JN.1 variant revealed unexpected results. Surprisingly, exhibited low disease manifestation animal model no weight loss or death control group. Still, assessment using clinical scoring system showed better protection for Ab94-treated mice, indicating still beneficial. Our work shows anti-receptor-binding mAb reactivity BA.2.86 emerged, anti-NTD was functional. Finally, adds insight into evolution virus by reporting is substantially less virulent than previous strains.

Язык: Английский

Процитировано

0