{"id":989,"date":"2025-06-13T06:56:50","date_gmt":"2025-06-13T06:56:50","guid":{"rendered":"http:\/\/scientificadvances.org\/?p=989"},"modified":"2025-06-13T06:56:50","modified_gmt":"2025-06-13T06:56:50","slug":"shown-is-the-heatmap-according-to-neutralizing-activity","status":"publish","type":"post","link":"https:\/\/scientificadvances.org\/?p=989","title":{"rendered":"\ufeffShown is the heatmap according to neutralizing activity"},"content":{"rendered":"

\ufeffShown is the heatmap according to neutralizing activity. with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of individuals generated substantial amounts of broadly neutralizing antibodies (bnAbs) against various SARS-CoV-2 variants, including Omicron sub-variants such as XBB. These bnAbs target four antigenic sites within the RBD. To determine the vulnerable site of SARS-CoV-2, we employed cryo-electron microscopy to identify the epitopes of highly potent bnAbs that targeted two major sites. Our findings provide immunological insights into the B cell responses elicited by RBD-based vaccine, and suggest that a vaccination regimen of prolonging UNC1079 time interval should be used in practice. Subject terms:Immunology, Structural biology UNC1079<\/a> == Introduction == Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing coronavirus disease 2019 (COVID-19), continues to undergo evolutionary changes, resulting in the emergency of new variants of concern (VOCs). Among these, the Omicron variant (B.1.1.529) emerged rapidly since November 2021, leading to subsequent waves of infections worldwide1. Omicron variant is characterized by significant mutation BCL3<\/a> in its spike (S) protein, which is a major target of vaccines. In particular, the receptor-binding domain (RBD) of the spike protein has undergone more than 15 amino acid substitutions, altering both the transmissibility and its recognition by the immune system2,3. Omicron variant contains several sub-variants that have emerged sequentially, including BA.1, to BA.2, BA.2.12.1, and currently circulating sub-variants BA.4\/5, BF.7, BQ.1\/1.1, and XBB. These sub-variants have shown reduced susceptibility to immunity induced by vaccines or previous infections49. To mitigate Omicron-related illnesses, vaccination strategies involving either primary immunization or booster doses with vaccines designed based on the ancestral virus or bivalent UNC1079 SARS-CoV-2 vaccines have been implemented globally10. Globally, numerous COVID-19 vaccines employing different strategies have been administered, targeting three major viral components: the whole virus, full-length S protein, and RBD1113. Infection with SARS-CoV-2 or immunization with whole virus-based inactivated vaccines or vaccines based on full-length spike protein, utilizing mRNA or adenovirus vector platforms, have demonstrated the ability to induce B cell responses against various SARS-CoV-2 variants, including Omicron sub-variants1420. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, which utilized a tandem-repeat dimeric RBD as the immunogen21,22. In a phase 3 trial, ZF2001 exhibited an efficacy of 81.4% in short-term follow-up and 75.7% in long-term follow-up23. ZF2001 has received approval in countries such as China, Uzbekistan, Indonesia, Colombia, and Kenya, with more than 300 million doses administered worldwide. In China, a three-dose regimen of ZF2001 is recommended to be completed within a 6-month period following the initial priming dose. Some recipients received three doses of ZF2001 with a 1-month interval between each dose due to urgent clinical requirements, while others had an extended dosing interval between the second and third doses up to five months, following the standard regimen for protein subunit vaccines like hepatitis B vaccine. Serologic data suggested that individuals with a longer dosing interval exhibited enhanced antibody responses compared to those with a shorter dosing interval. Specifically, these individuals displayed increased potency and breadth of UNC1079 neutralizing antibodies against SARS-CoV-2 and its variants, including Omicron sub-variants4,24,25. Based on the finding regarding serologic antibody responses, our study aimed to examine the landscape of B-cell receptor (BCR) induced by the RBD-based vaccine ZF2001 in individuals with different dosing intervals. Additionally, we aimed to investigate the breadth of vaccine-induced responses to major VOCs and Omicron sub-variants at the monoclonal antibody (mAb) level. The epitopes targeted by broadly neutralizing (bnAbs) were determined using competition assay and cryo-electron microscopy (cryo-EM). The data obtained from our study provide valuable immunological insights into the impact of dosing interval on the quality of B cell responses in the context of vaccination of an RBD-based COVID-19 vaccine. These findings suggest the need to optimize vaccination regimens in practice setting and highlight the important of developing future vaccines with a broader spectrum of protection. == Results == == Serologic antibody responses == We analyzed the antibody responses in serum samples of 12 individuals after receipt of three doses of ZF2001 vaccine from a cohort recruited previously (Supplementary Fig.S1)24. Six individuals had received three doses of vaccine at month 0, 1, and 2 (short-interval group). The other six individuals had received three doses of vaccine at month 0, 1, and 46, with.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeffShown is the heatmap according to neutralizing activity. with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[35],"tags":[],"class_list":["post-989","post","type-post","status-publish","format-standard","hentry","category-histone-methyltransferases"],"_links":{"self":[{"href":"https:\/\/scientificadvances.org\/index.php?rest_route=\/wp\/v2\/posts\/989","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scientificadvances.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scientificadvances.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scientificadvances.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/scientificadvances.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=989"}],"version-history":[{"count":1,"href":"https:\/\/scientificadvances.org\/index.php?rest_route=\/wp\/v2\/posts\/989\/revisions"}],"predecessor-version":[{"id":990,"href":"https:\/\/scientificadvances.org\/index.php?rest_route=\/wp\/v2\/posts\/989\/revisions\/990"}],"wp:attachment":[{"href":"https:\/\/scientificadvances.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=989"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scientificadvances.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=989"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scientificadvances.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=989"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}