tetano
Editor, Senior Moderator
J Exp Med
. 2025 Dec 1;222(12):e20251146.
doi: 10.1084/jem.20251146. Epub 2025 Oct 9. Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2
Siriruk Changrob[SUP] 1 [/SUP], Atsuhiro Yasuhara[SUP] 1 [/SUP], Suncheol Park[SUP] 2 [/SUP], Sandhya Bangaru[SUP] 2 [/SUP], Lei Li[SUP] 1 [/SUP], Chloe A Troxell[SUP] 1 [/SUP], Peter J Halfmann[SUP] 3 [/SUP], Steven A Erickson[SUP] 4 [/SUP], Nicholas J Catanzaro[SUP] 5 [/SUP], Meng Yuan[SUP] 2 [/SUP], Panpan Zhou[SUP] 6 [/SUP], Min Huang[SUP] 1 [/SUP], G Dewey Wilbanks[SUP] 1 [/SUP], Joshua J C McGrath[SUP] 1 [/SUP], Gagandeep Singh[SUP] 7 [/SUP], Sean A Nelson[SUP] 1 [/SUP], Yanbin Fu[SUP] 1 [/SUP], Nai-Ying Zheng[SUP] 1 [/SUP], Sofia M Carayannopoulos[SUP] 1 [/SUP], Haley L Dugan[SUP] 4 [/SUP], Dustin G Shaw[SUP] 4 [/SUP], Christopher T Stamper[SUP] 4 [/SUP], Maria Lucia L Madariaga[SUP] 8 [/SUP], Florian Krammer[SUP] 7 9 10 [/SUP], Raiees Andrabi[SUP] 6 [/SUP], Dennis R Burton[SUP] 6 11 [/SUP], Andrew B Ward[SUP] 2 [/SUP], Ian A Wilson[SUP] 2 12 [/SUP], Yoshihiro Kawaoka[SUP] 3 13 14 [/SUP], Patrick C Wilson[SUP] 1 [/SUP]
Affiliations
The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. However, antibodies targeting this region are typically non-neutralizing. We report herein that S2-targeting antibodies from patients who recovered from SARS-CoV-2 infection bound only closely related sarbecovirus subgenus strains and, like most known S2 antibodies, none of these were neutralizing. In contrast, first-exposure, severe acutely infected COVID-19 patients predominantly induced back-boosted antibody-secreting cells imprinted against past common cold coronavirus strain OC43 that were cross-reactive to as many as five subgenera of betacoronavirus strains and gave rise to antibodies that were neutralizing and protective. The antibodies targeted two different sites: one defined by competition with stem helix antibodies, and the second to an underdescribed epitope at the apex of S2. These findings suggest that S2-targeted vaccines could strategically exploit controlled OC43 priming followed by SARS-CoV-2 boosting to enhance the breadth and quality of protective antibody responses.
. 2025 Dec 1;222(12):e20251146.
doi: 10.1084/jem.20251146. Epub 2025 Oct 9. Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2
Siriruk Changrob[SUP] 1 [/SUP], Atsuhiro Yasuhara[SUP] 1 [/SUP], Suncheol Park[SUP] 2 [/SUP], Sandhya Bangaru[SUP] 2 [/SUP], Lei Li[SUP] 1 [/SUP], Chloe A Troxell[SUP] 1 [/SUP], Peter J Halfmann[SUP] 3 [/SUP], Steven A Erickson[SUP] 4 [/SUP], Nicholas J Catanzaro[SUP] 5 [/SUP], Meng Yuan[SUP] 2 [/SUP], Panpan Zhou[SUP] 6 [/SUP], Min Huang[SUP] 1 [/SUP], G Dewey Wilbanks[SUP] 1 [/SUP], Joshua J C McGrath[SUP] 1 [/SUP], Gagandeep Singh[SUP] 7 [/SUP], Sean A Nelson[SUP] 1 [/SUP], Yanbin Fu[SUP] 1 [/SUP], Nai-Ying Zheng[SUP] 1 [/SUP], Sofia M Carayannopoulos[SUP] 1 [/SUP], Haley L Dugan[SUP] 4 [/SUP], Dustin G Shaw[SUP] 4 [/SUP], Christopher T Stamper[SUP] 4 [/SUP], Maria Lucia L Madariaga[SUP] 8 [/SUP], Florian Krammer[SUP] 7 9 10 [/SUP], Raiees Andrabi[SUP] 6 [/SUP], Dennis R Burton[SUP] 6 11 [/SUP], Andrew B Ward[SUP] 2 [/SUP], Ian A Wilson[SUP] 2 12 [/SUP], Yoshihiro Kawaoka[SUP] 3 13 14 [/SUP], Patrick C Wilson[SUP] 1 [/SUP]
Affiliations
- PMID: 41066082
- DOI: 10.1084/jem.20251146
The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. However, antibodies targeting this region are typically non-neutralizing. We report herein that S2-targeting antibodies from patients who recovered from SARS-CoV-2 infection bound only closely related sarbecovirus subgenus strains and, like most known S2 antibodies, none of these were neutralizing. In contrast, first-exposure, severe acutely infected COVID-19 patients predominantly induced back-boosted antibody-secreting cells imprinted against past common cold coronavirus strain OC43 that were cross-reactive to as many as five subgenera of betacoronavirus strains and gave rise to antibodies that were neutralizing and protective. The antibodies targeted two different sites: one defined by competition with stem helix antibodies, and the second to an underdescribed epitope at the apex of S2. These findings suggest that S2-targeted vaccines could strategically exploit controlled OC43 priming followed by SARS-CoV-2 boosting to enhance the breadth and quality of protective antibody responses.