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An Engineered IgG-VHH Bispecific Antibody against SARS-CoV-2 and Its Variants

Small methods

2022 Oct 27

Chi, H;Wang, L;Liu, C;Cheng, X;Zheng, H;Lv, L;Tan, Y;Zhang, N;Zhao, S;Wu, M;Luo, D;Qiu, H;Feng, R;Fu, W;Zhang, J;Xiong, X;Zhang, Y;Zu, S;Chen, Q;Ye, Q;Yan, X;Hu, Y;Zhang, Z;Yan, R;Yin, J;Lei, P;Wang, W;Lang, G;Shao, J;Deng, Y;Wang, X;Qin, C;
PMID: 36300882 | DOI: 10.1002/smtd.202200932

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies are shown to be effective therapeutics for providing coronavirus disease 2019 (COVID-19) protection. However, recurrent variants arise and facilitate significant escape from current antibody therapeutics. Bispecific antibodies (bsAbs) represent a unique platform to increase antibody breadth and to reduce neutralization escape. Herein, a novel immunoglobulin G-variable domains of heavy-chain-only antibody (IgG-VHH) format bsAb derived from a potent human antibody R15-F7 and a humanized nanobody P14-F8-35 are rationally engineered. The resulting bsAb SYZJ001 efficiently neutralizes wild-type SARS-CoV-2 as well as the alpha, beta, gamma, and delta variants, with superior efficacy to its parental antibodies. Cryo-electron microscopy structural analysis reveals that R15-F7 and P14-F8-35 bind to nonoverlapping epitopes within the RBD and sterically hindered ACE2 receptor binding. Most importantly, SYZJ001 shows potent prophylactic and therapeutic efficacy against SARS-CoV-2 in three established mouse models. Collectively, the current results demonstrate that the novel bsAb format is feasible and effective, suggesting great potential as an inspiring antiviral strategy.

Rational development of a combined mRNA vaccine against COVID-19 and influenza

NPJ vaccines

2022 Jul 26

Ye, Q;Wu, M;Zhou, C;Lu, X;Huang, B;Zhang, N;Zhao, H;Chi, H;Zhang, X;Ling, D;Zhang, RR;Li, Z;Luo, D;Huang, YJ;Qiu, HY;Song, H;Tan, W;Xu, K;Ying, B;Qin, CF;
PMID: 35882870 | DOI: 10.1038/s41541-022-00478-w

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor-binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

In situ detection of vaccine mRNA in the cytoplasm of hepatocytes during COVID19 vaccine-related hepatitis

Journal of hepatology

2022 Sep 15

Martin-Navarro, L;de Andrea, C;Sangro, B;Argemi, J;
PMID: 36116717 | DOI: 10.1016/j.jhep.2022.08.039

Spike Protein-independent Attenuation of SARS-CoV-2 Omicron Variant in Laboratory Mice

Cell Reports

2022 Aug 01

Liu, S;Selvaraj, P;Sangare, K;Luan, B;Wang, T;
| DOI: 10.1016/j.celrep.2022.111359

Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration; Silver Spring, Maryland, USA, 20993

HISTOLOGICAL FINDINGS IN TRANSBRONCHIAL CRYOBIOPSIES OBTAINED FROM PATIENTS AFTER COVID-19

Chest

2021 Sep 25

Culebras, M;Loor, K;Sansano, I;Persiva, Ó;Clofent, D;Polverino, E;Felipe, A;Osorio, J;Muñoz, X;Álvarez, A;Se-COVID-19 team, ;
PMID: 34582842 | DOI: 10.1016/j.chest.2021.09.016

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

Science advances

2021 Sep 10

Bewley, KR;Gooch, K;Thomas, KM;Longet, S;Wiblin, N;Hunter, L;Chan, K;Brown, P;Russell, RA;Ho, C;Slack, G;Humphries, HE;Alden, L;Allen, L;Aram, M;Baker, N;Brunt, E;Cobb, R;Fotheringham, S;Harris, D;Kennard, C;Leung, S;Ryan, K;Tolley, H;Wand, N;White, A;Sibley, L;Sarfas, C;Pearson, G;Rayner, E;Xue, X;Lambe, T;Charlton, S;Gilbert, S;Sattentau, QJ;Gleeson, F;Hall, Y;Funnell, S;Sharpe, S;Salguero, FJ;Gorringe, A;Carroll, M;
PMID: 34516768 | DOI: 10.1126/sciadv.abg7996

[Figure: see text].

Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19

The Lancet. Respiratory medicine

2021 Jun 09

Ceulemans, LJ;Khan, M;Yoo, SJ;Zapiec, B;Van Gerven, L;Van Slambrouck, J;Vanstapel, A;Van Raemdonck, D;Vos, R;Wauters, E;Wauters, J;Carmeliet, P;Mombaerts, P;
PMID: 34118186 | DOI: 10.1016/S2213-2600(21)00240-X

ACE2 expression is regulated by AhR in SARS-CoV-2-infected macaques

Cellular & molecular immunology

2021 Apr 01

Lv, J;Yu, P;Wang, Z;Deng, W;Bao, L;Liu, J;Li, F;Zhu, Q;Zhou, N;Lv, Q;Wang, G;Wang, S;Zhou, Y;Song, J;Tong, WM;Liu, Y;Qin, C;Huang, B;
PMID: 33795851 | DOI: 10.1038/s41423-021-00672-1

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	Description
sense Example: Hs-LAG3-sense	Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron# Example: Mm-Htt-intron2	Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)	A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp Example: Hs-PDGFB-No-XMm	Does not cross detect with the species (Sp)
XSp Example: Rn-Pde9a-XMm	designed to cross detect with the species (Sp)
O# Example: Mm-Islr-O1	Alternative design targeting different regions of the same transcript or isoforms
CDS Example: Hs-SLC31A-CDS	Probe targets the protein-coding sequence only
EnEm	Probe targets exons n and m
En-Em	Probe targets region from exon n to exon m
Retired Nomenclature
tvn Example: Hs-LEPR-tv1	Designed to target transcript variant n
ORF Example: Hs-ACVRL1-ORF	Probe targets open reading frame
UTR Example: Hs-HTT-UTR-C3	Probe targets the untranslated region (non-protein-coding region) only
5UTR Example: Hs-GNRHR-5UTR	Probe targets the 5' untranslated region only
3UTR Example: Rn-Npy1r-3UTR	Probe targets the 3' untranslated region only
Pan Example: Pool	A mixture of multiple probe sets targeting multiple genes or transcripts

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