AbstractHematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.5) SARS-CoV-2 booster vaccination in MM patients.

摘要血液系统恶性肿瘤与SARS-CoV-2感染期间并发症的风险增加有关。初级系列或单价加强疫苗可降低多发性骨髓瘤患者的疾病严重程度，住院率和死亡率。我们在MM患者中对单价（WA1）或二价（WA1/BA.5）SARS-CoV-2加强疫苗接种后的病毒中和和尖峰结合抗体谱进行了表征。

Bivalent vaccination improved the breadth of binding antibodies but not neutralization activity against contemporary variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity..

二价疫苗接种改善了结合抗体的广度，但没有改善针对当代变体的中和活性。混合免疫和免疫印迹影响疫苗引发的免疫力。。

IntroductionHematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections1,2. Although vaccines have led to reduced risk of complications, vaccinated patients with hematologic malignancies still have a higher risk of hospitalization3, as well as developing chronic SARS-CoV-2 infections4,5,6, which have resulted in intrahost viral evolution and the emergence of variants of concern7,8,9.

引言血液系统恶性肿瘤与SARS-CoV-2感染期间并发症的风险增加有关1,2。虽然疫苗已经降低了并发症的风险，但接种疫苗的恶性血液病患者仍然有较高的住院风险3，以及发展为慢性SARS-CoV-2感染4,5,6，这导致了宿主内病毒进化和出现变异的关注7,8,9。

Impaired induction of neutralizing antibodies (nAbs) against SARS-CoV-2 Omicron variants has been reported in multiple myeloma (MM) patients following booster immunization with monovalent vaccines10. Bivalent mRNA vaccines include both the ancestral WA1 and BA.4/5 spike. However, little is known about the breadth of nAbs induced by additional booster immunizations or immunization with monovalent or bivalent vaccines.

据报道，在用单价疫苗加强免疫后，多发性骨髓瘤（MM）患者中针对SARS-CoV-2 Omicron变体的中和抗体（NAb）的诱导受损10。二价mRNA疫苗包括祖先WA1和BA.4/5穗。然而，关于额外的加强免疫或单价或二价疫苗免疫诱导的NAb的广度知之甚少。

In this study, we used an in vitro, live virus focus reduction neutralization test (FRNT) to determine the neutralization activity against WA1, BA.1, BA.5, BQ.1.1, and the contemporary XBB.1.5 Omicron subvariant in cohorts of MM patients that received monovalent or bivalent booster immunizations. We also evaluated spike-binding antibody responses against this panel of viruses using a Spike-specific electrochemiluminescence assay11.

在这项研究中，我们使用体外活病毒焦点减少中和试验（FRNT）来确定在接受单价或二价加强免疫的MM患者队列中对WA1，BA.1，BA.5，BQ.1.1和当代XBB.1.5 Omicron亚变体的中和活性。我们还使用尖峰特异性电化学发光测定法评估了针对这组病毒的尖峰结合抗体反应11。

All the participants provided written informed consent, and the Institutional Review Board of Emory University approved the study.Results and discussionThe study included two cohorts. The first cohort received anti-SARS-CoV-2 primary immunization and two monovalent booster immunizations, with the last monovalent booster administered 1–6 months after the second dose (n = 101, Supplementary Fig.

所有参与者都提供了书面知情同意书，埃默里大学的机构审查委员会批准了这项研究。。第一组接受了抗SARS-CoV-2初次免疫和两次单价加强免疫，最后一次单价加强免疫在第二次给药后1-6个月给予（n=101，补充图）。

1). The second cohort received the anti-SARS-CoV-2 primary immunization, two booster immunizations, and a bi.

1） 。第二组接受了抗SARS-CoV-2初次免疫，两次加强免疫和一次bi。

Data availability

数据可用性

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

支持本研究结果的数据可根据合理要求从通讯作者处获得。

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Download referencesAcknowledgementsThis work was supported in part by grants (NIH P51OD011132, 3U19AI057266-17S1, 1U54CA260563, HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Emory Executive Vice President for Health Affairs Synergy Fund award, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award.

下载参考文献致谢这项工作部分得到了埃默里大学国家过敏与传染病研究所（NIAID）、国立卫生研究院（NIH）、埃默里卫生事务协同基金奖执行副总裁、亚特兰大儿童感染与疫苗和儿童保健儿科研究联盟中心、伍德拉夫伍德拉夫健康科学中心和埃默里医学院的COVID-Catalyst-I3基金的资助（NIH P51OD011132、3U19AI057266-17S1、1U54CA260563、HHSN2722014004C、NIH/NIAID CEIRR）健康科学中心2020年新型冠状病毒肺炎治愈奖。

This work was also supported in part by NCI U54 Seronet award CA260563. MVD is also partly supported by funds from the NIH R35CA197603 and the SCOR award from LLS. KMD is partly supported by funds from NIH CA238471 and AR077926, and LLS. Authors acknowledge the support of Cancer Tissue and Pathology, Data and Technology Applications, and Biostatistics shared resource of the Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.

这项工作也得到了NCI U54 Seronet award CA260563的部分支持。MVD还得到了NIH R35CA197603的资金和LLS的SCOR奖的部分支持。KMD的部分资金来自NIH CA238471和AR077926以及LLS。作者感谢埃默里大学Winship癌症研究所和NIH/NCI的癌症组织和病理学，数据和技术应用以及生物统计学共享资源的支持，奖项编号为P30CA138292。

Funders played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.Author informationAuthor notesThese authors contributed equally: Madhav V.

资助者在研究的设计和实施中没有发挥任何作用；数据的收集、管理、分析和解释；稿件的准备，审查或批准；并决定提交稿件出版。作者信息作者注意到这些作者做出了同样的贡献：Madhav V。

Dhodapkar, Mehul S. Suthar.Authors and AffiliationsEmory Vaccine Center, Emory University, Atlanta, GeorgiaAlberto Moreno, Kelly Manning, Madison Ellis, Bushra Wali & Mehul S. SutharEmory National Primate Research Center, Atlanta, GeorgiaAlberto Moreno, Kelly Manning, Madison Ellis, Bushra Wali & Mehul S.

Dhodapkar，Mehul S.Suthar。作者和附属机构亚特兰大埃默里大学莫里疫苗中心，乔治亚·阿尔贝托·莫雷诺，凯利·曼宁，麦迪逊·埃利斯，布什拉·瓦利和梅胡尔S.萨塔雷默里国家灵长类动物研究中心，亚特兰大，乔治亚·阿尔贝托·莫雷诺，凯利·曼宁，麦迪逊·埃利斯，布什拉·瓦利和梅胡尔S。

SutharDivision of Infectious Diseases, D.

传染病SutharDivision，D。

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PubMed Google ScholarContributionsA.M., Collected, analyzed, interpreted data, and wrote the original draft. K.M., M.I.A., M.E., and B.W., Performed assays. A.K.N., R.J.M., J.L.K., C.C.H., N.S.J., and S.L., Writing review and editing. J.M.S., Performed statistical analysis. K.M.D, Resources, formal analysis.

PubMed谷歌学术贡献。M、 ，收集，分析，解释数据并撰写原始草案。K、 。A、 K.N.，R.J.M.，J.L.K.，C.C.H.，N.S.J。和S.L.，写作评论和编辑。J、 M.S.进行了统计分析。K、 医学博士，资源，形式分析。

M.V.D., and M.S.S., Conceptualization, resources, funding acquisition, writing review, and editing.Corresponding authorsCorrespondence to.

M、 。通讯作者通讯。

Madhav V. Dhodapkar or Mehul S. Suthar.Ethics declarations

Madhav V.Dhodapkar或Mehul S.Suthar。道德宣言

Competing interests

相互竞争的利益

A.M. reports grants from NIH during the conduct of the study. J.L.K. reports grants from NIH during the conduct of the study and personal fees from AbbVie, BMS, Janssen, and Incyte outside the submitted work. S.L. reports personal fees from Amgen, grants and personal fees from Takeda, Janssen, and BMS, personal fees from Pfizer, Genentech, AbbVie, and Celgene outside the submitted work; and Board of Directors TG Therapeutics with stock.

A、 M.在研究期间报告了NIH的资助。J、 L.K.在研究期间报告了美国国立卫生研究院的拨款，以及AbbVie，BMS，Janssen和Incyte在提交的作品之外的个人费用。S.L.报告了安进的个人费用，武田，Janssen和BMS的拨款和个人费用，辉瑞，Genentech，AbbVie和Celgene在提交的作品之外的个人费用；和董事会TG Therapeutics with stock。

M.V.D. personal fees from Sanofi, BMS, and Lava Therapeutics outside the submitted work. M.S.S. reports grants and personal fees from Moderna and Ocugen outside the submitted work. No disclosures were reported by the other authors..

M、 V.D.赛诺菲，BMS和Lava Therapeutics在提交的作品之外的个人费用。M.S.S.报告了Moderna和Ocugen在提交的作品之外的赠款和个人费用。其他作者没有披露任何信息。。

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Reprints and permissionsAbout this articleCite this articleMoreno, A., Manning, K., Azeem, M.I. et al. Divergence of variant antibodies following SARS-CoV-2 booster vaccines in myeloma and impact of hybrid immunity.

转载和许可本文引用本文Moreno，A.，Manning，K.，Azeem，M.I。等人。SARS-CoV-2增强疫苗在骨髓瘤中的变异抗体的差异和混合免疫的影响。

npj Vaccines 9, 201 (2024). https://doi.org/10.1038/s41541-024-00999-6Download citationReceived: 24 August 2023Accepted: 17 October 2024Published: 27 October 2024DOI: https://doi.org/10.1038/s41541-024-00999-6Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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