Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages
Abstract The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as one of the most immune-evasive varian...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02139-5 |
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| author | Jingyun Yang Xuemei He Huashan Shi Cai He Hong Lei Heng He Li Yang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Zhenling Wang Guangwen Lu Jiong Li Yuquan Wei |
| author_facet | Jingyun Yang Xuemei He Huashan Shi Cai He Hong Lei Heng He Li Yang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Zhenling Wang Guangwen Lu Jiong Li Yuquan Wei |
| author_sort | Jingyun Yang |
| collection | DOAJ |
| description | Abstract The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as one of the most immune-evasive variants, showing higher neutralization resistance compared to XBB.1.5. In this study, serum samples were collected from adult participants including those who had gone through the BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infection waves, characterized by different infection and vaccination histories. We evaluated the neutralization in these serum samples against pseudoviruses of Omicron lineages. We further investigated humoral immune response of recombinant XBB vaccines against Omicron variants and estimated the neutralization resistance of JN.1 sublineages, including KP.2 and KP.3. Our results showed that sera from previous circulating Omicron subvariant breakthrough infections exhibited low neutralization against pseudoviruses of Omicron lineages. The GMTs of 50% neutralization against all tested pseudoviruses were significantly elevated in sera from individuals who received WSK-V102C or WSK-V102D boosters. Importantly, the GMTs of 50% neutralization in serum samples from individuals 4 months after a WSK-V102D booster against XBB.1.5, JN.1, JN.1.13, KP.2 and KP.3 pseudoviruses were 3479, 1684, 1397, 1247 and 1298, with 9.86-, 9.79-, 8.73-, 8.66- and 8.16-fold increase compared to those without booster, respectively, indicating that boosting with XBB.1.5 subunit vaccines still induced strong antibody responses against JN.1 sublineages. However, JN.1 sublineages, including KP.2 and KP.3, revealed more than 2-fold decreases in neutralizing antibody titers compared to XBB.1.5, suggesting significantly enhanced neutralization evasion and the necessity of boosters based on JN.1, KP.2 or KP.3. |
| format | Article |
| id | doaj-art-122e5addc31648d2bb95365447d89d97 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-122e5addc31648d2bb95365447d89d972025-02-02T12:44:31ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-0110111110.1038/s41392-025-02139-5Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineagesJingyun Yang0Xuemei He1Huashan Shi2Cai He3Hong Lei4Heng He5Li Yang6Wei Wang7Guobo Shen8Jinliang Yang9Zhiwei Zhao10Xiangrong Song11Zhenling Wang12Guangwen Lu13Jiong Li14Yuquan Wei15Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityAbstract The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as one of the most immune-evasive variants, showing higher neutralization resistance compared to XBB.1.5. In this study, serum samples were collected from adult participants including those who had gone through the BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infection waves, characterized by different infection and vaccination histories. We evaluated the neutralization in these serum samples against pseudoviruses of Omicron lineages. We further investigated humoral immune response of recombinant XBB vaccines against Omicron variants and estimated the neutralization resistance of JN.1 sublineages, including KP.2 and KP.3. Our results showed that sera from previous circulating Omicron subvariant breakthrough infections exhibited low neutralization against pseudoviruses of Omicron lineages. The GMTs of 50% neutralization against all tested pseudoviruses were significantly elevated in sera from individuals who received WSK-V102C or WSK-V102D boosters. Importantly, the GMTs of 50% neutralization in serum samples from individuals 4 months after a WSK-V102D booster against XBB.1.5, JN.1, JN.1.13, KP.2 and KP.3 pseudoviruses were 3479, 1684, 1397, 1247 and 1298, with 9.86-, 9.79-, 8.73-, 8.66- and 8.16-fold increase compared to those without booster, respectively, indicating that boosting with XBB.1.5 subunit vaccines still induced strong antibody responses against JN.1 sublineages. However, JN.1 sublineages, including KP.2 and KP.3, revealed more than 2-fold decreases in neutralizing antibody titers compared to XBB.1.5, suggesting significantly enhanced neutralization evasion and the necessity of boosters based on JN.1, KP.2 or KP.3.https://doi.org/10.1038/s41392-025-02139-5 |
| spellingShingle | Jingyun Yang Xuemei He Huashan Shi Cai He Hong Lei Heng He Li Yang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Zhenling Wang Guangwen Lu Jiong Li Yuquan Wei Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages Signal Transduction and Targeted Therapy |
| title | Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages |
| title_full | Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages |
| title_fullStr | Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages |
| title_full_unstemmed | Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages |
| title_short | Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages |
| title_sort | recombinant xbb 1 5 boosters induce robust neutralization against kp 2 and kp 3 included jn 1 sublineages |
| url | https://doi.org/10.1038/s41392-025-02139-5 |
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