tetano
Editor, Senior Moderator
J Infect
. 2026 Aug 11:106827.
doi: 10.1016/j.jinf.2026.106827. Online ahead of print.
Cross-Neutralizing Antibody Responses to Diverse Coronaviruses in the Human Population
Shixiong Zhou[SUP] 1 [/SUP], Chunhai Liu[SUP] 2 [/SUP], Weiyong Liu[SUP] 3 [/SUP], Kun Cai[SUP] 4 [/SUP], Ke Lan[SUP] 5 [/SUP], Chengliang Zhu[SUP] 6 [/SUP], Qian Wang[SUP] 7 [/SUP], Lihong Liu[SUP] 8 [/SUP]
Affiliations
The COVID-19 pandemic has substantially reshaped population humoral immunity. However, whether individuals in the post-pandemic era have developed broader cross-neutralizing antibody responses against diverse coronaviruses remains unclear. To address this question, we evaluated serum neutralizing activity in 869 individuals from Wuhan, China, including 78 pre-pandemic samples collected in 2017 and 791 post-pandemic samples collected in 2025. Compared with pre-pandemic sera, post-pandemic sera exhibited enhanced neutralizing activity against multiple sarbecoviruses and the merbecovirus MjHKU4r-CoV-1, with mean viral inhibition increasing by 1.7% to 76.5% at a 1:20 serum dilution, most prominently against clade 1b sarbecoviruses. In contrast, no appreciable enhancement was observed against endemic human alphacoronaviruses or MERS-CoV. Neutralizing responses were strongly correlated across sarbecoviruses, particularly within clade 1b. Antigenic mapping showed that genetic relatedness did not reliably predict antigenic relationships, as Pangolin-GD, Pangolin-GX, and Khosta-2 were genetically more divergent yet antigenically closer to ancestral SARS-CoV-2 (D614G) than contemporary SARS-CoV-2 variants. Notably, both cohorts robustly neutralized Khosta-2, primarily through S1-directed antibodies, suggesting pre-existing cross-reactive immunity induced by endemic human coronaviruses that was further boosted by SARS-CoV-2 exposure. Collectively, these findings demonstrate that post-pandemic sera exhibit enhanced cross-neutralizing antibody responses predominantly against sarbecoviruses, potentially strengthening population immunity against related zoonotic sarbecoviruses and increasing the immunological barrier to their emergence in humans.
Keywords: Coronaviruses; SARS-CoV-2; antigenic cartography; cross-neutralizing antibodies; genetic distance; humoral immunity; pseudovirus neutralization.
. 2026 Aug 11:106827.
doi: 10.1016/j.jinf.2026.106827. Online ahead of print.
Cross-Neutralizing Antibody Responses to Diverse Coronaviruses in the Human Population
Shixiong Zhou[SUP] 1 [/SUP], Chunhai Liu[SUP] 2 [/SUP], Weiyong Liu[SUP] 3 [/SUP], Kun Cai[SUP] 4 [/SUP], Ke Lan[SUP] 5 [/SUP], Chengliang Zhu[SUP] 6 [/SUP], Qian Wang[SUP] 7 [/SUP], Lihong Liu[SUP] 8 [/SUP]
Affiliations
- PMID: 42580488
- DOI: 10.1016/j.jinf.2026.106827
The COVID-19 pandemic has substantially reshaped population humoral immunity. However, whether individuals in the post-pandemic era have developed broader cross-neutralizing antibody responses against diverse coronaviruses remains unclear. To address this question, we evaluated serum neutralizing activity in 869 individuals from Wuhan, China, including 78 pre-pandemic samples collected in 2017 and 791 post-pandemic samples collected in 2025. Compared with pre-pandemic sera, post-pandemic sera exhibited enhanced neutralizing activity against multiple sarbecoviruses and the merbecovirus MjHKU4r-CoV-1, with mean viral inhibition increasing by 1.7% to 76.5% at a 1:20 serum dilution, most prominently against clade 1b sarbecoviruses. In contrast, no appreciable enhancement was observed against endemic human alphacoronaviruses or MERS-CoV. Neutralizing responses were strongly correlated across sarbecoviruses, particularly within clade 1b. Antigenic mapping showed that genetic relatedness did not reliably predict antigenic relationships, as Pangolin-GD, Pangolin-GX, and Khosta-2 were genetically more divergent yet antigenically closer to ancestral SARS-CoV-2 (D614G) than contemporary SARS-CoV-2 variants. Notably, both cohorts robustly neutralized Khosta-2, primarily through S1-directed antibodies, suggesting pre-existing cross-reactive immunity induced by endemic human coronaviruses that was further boosted by SARS-CoV-2 exposure. Collectively, these findings demonstrate that post-pandemic sera exhibit enhanced cross-neutralizing antibody responses predominantly against sarbecoviruses, potentially strengthening population immunity against related zoonotic sarbecoviruses and increasing the immunological barrier to their emergence in humans.
Keywords: Coronaviruses; SARS-CoV-2; antigenic cartography; cross-neutralizing antibodies; genetic distance; humoral immunity; pseudovirus neutralization.