Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents

Cao, Yunlong; Jian, Fanchong; Zhang, Zhiying; Yisimayi, Ayijiang; Hao, Xiaohua; Bao, Linlin; Yuan, Fei; Yu, Yuanling; Du, Shuo; Wang, Jing; Xiao, Tianhe; Song, Weiliang; Zhang, Ying; Liu, Pulan; An, Ran; Wang, Peng; Wang, Yao; Yang, Sijie; Xiao, Ning; Zhang, Yuhang; Gu, Qingqing; Shao, Fei; Hu, Yaling; Yin, Weidong; Zheng, Aihua; Wang, Youchun; Qin, Chuan; Jin, Ronghua; Xiao, Junyu; Xie, X. Sunney

doi:10.1016/j.celrep.2022.111845

Cited by 81 publications

(84 citation statements)

References 63 publications

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“…However, LY-CoV1404 was escaped by BJ.1, XBB, BR.1, CH.1.1, BA.4.6.3 and BQ.1.1 while exhibiting strongly reduced activity against BA.2.38.1, BA.5.6.2 and BQ.1 due to K444N/T mutations and the combination of K444M–G446S or V445P–G446S 26 . SA55 + SA58 is a pair of broad NAbs isolated from vaccinated individuals who had SARS that target non-competing conserved epitopes 2 , 27 . SA58 is weak to G339H and R346T mutations and showed reduced neutralization efficacy against BJ.1/XBB and BA.2.75 sublineages.…”

Section: Antibody Evasion By Convergent Variantsmentioning

confidence: 99%

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Cao

Jian

Wang

et al. 2022

Nature

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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Section: Antibody Evasion By Convergent Variantsmentioning

confidence: 99%

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Cao

Jian

Wang

et al. 2022

Nature

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448

578

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“…Preclinical studies found that RBD protein can induce both humoral immunity and T cell immune response in animals and exhibit protection against SARS-CoV-2 challenge [ 6 , 7 , 8 ]. Furthermore, the RBD contains multiple neutralizing epitopes, several RBD-binding monoclonal antibodies (mAbs), such as REGN10933, REGN10987 [ 9 ], HB27 [ 10 ], H89Y [ 11 ], S309 [ 12 ], SA58, and SA55 [ 13 ], exhibit great neutralizing potency or cross-neutralizing activity against SARS-CoV-2 and SARS-CoV. Therefore, RBD can be considered as an effective target of the SARS-CoV-2 vaccine.…”

Section: Introductionmentioning

confidence: 99%

A Polysaccharide-RBD-Fc-Conjugated COVID-19 Vaccine, SCTV01A, Showed High Immunogenicity and Low Toxicity in Animal Models

et al. 2023

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We previously developed a polysaccharide-–RBD-conjugated nanoparticle vaccine which induced protective efficacy against SARS-CoV-2 in a mouse model. Here, we newly developed a vaccine, SCTV01A, by chemically conjugating recombinant SARS-CoV-2 RBD-Fc and PPS14 (Streptococcus pneumoniae serotype type 14 capsular polysaccharide). The immunogenicity and toxicity of SCTV01A were evaluated in animal models. The PPS14 conjugation enhanced the immunogenicity of RBD-Fc in C57BL/6 mice whether formulated with SCT-VA02B or Alum adjuvant. SCTV01A also induced high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. In addition, SCTV01A stimulated potent neutralizing titers in rhesus macaques and effectively reduced lung inflammation after SARS-CoV-2 infection with neither antibody-dependent enhancement (ADE) nor vaccine-enhanced diseases (VED) phenomenon. Importantly, the long-term toxicity study of SCTV01A in rhesus macaques did not cause any abnormal toxicity and was tolerated at the highest tested dose (120 μg). The existing immunogenicity and toxicological evaluation results have demonstrated the safety and efficacy of SCTV01A, which will be a promising and feasible vaccine to protect against SARS-CoV-2 infection.

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“…Thus, polyclonal neutralizing antibodies or multi-specific neutralizing antibodies should be developed to neutralize of SARS-CoV-2 more effectively. It suggested that NAbs integrated into “cocktails” are now in clinical implementation ( 38 ). However, such NAbs are rather expensive to produce and the implemented design, production and purification strategies need to be improved.…”

Section: Discussionmentioning

confidence: 99%

Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects

Li¹,

Liang²,

Hei³

et al. 2022

Front. Immunol.

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IntroductionAn approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methodsThe novel N-IgY-pAb and its intranasal spray response against the wild type (“‘WH-Human 1”) SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray.ResultsSeventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121).Discussion and conclusionWe concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and “cocktails” of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.

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Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents

Cited by 81 publications

References 63 publications

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

A Polysaccharide-RBD-Fc-Conjugated COVID-19 Vaccine, SCTV01A, Showed High Immunogenicity and Low Toxicity in Animal Models

Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects

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