Cross-neutralization of distant coronaviruses correlates with Spike S2-specific antibodies from immunocompetent and immunocompromised vaccinated SARS-CoV-2-infected patients.

Autor:	Patel SV; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Leeman BM; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Botros PJ; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Folta J; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Shahid D; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Rocque AI; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Joyal AS; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Vecchio JA; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Passell E; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Tien D; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Reynolds Z; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Su K; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Vyas TD; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Vyas JM; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Abar E; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Barry M; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Alexandrescu A; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Wallace Z; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., DaCosta JM; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA., Choudhary MC; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Tamura T; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Edelstein G; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Li Y; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Deo R; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Sparks JA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Boucau J; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA., Glover O; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA., Barczak A; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA., Lemieux J; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Siedner MJ; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA., Li JZ; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Fofana IB; Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Dec 05. Date of Electronic Publication: 2024 Dec 05.
DOI:	10.21203/rs.3.rs-5487774/v1
Abstrakt:	As of May 2023, the public health emergency of COVID-19 was lifted across the globe. However, SARS-CoV-2 infections continue to be recorded worldwide. This situation has been attributed to the ability of the virus to evade host immune responses including neutralizing antibody-derived Immunity. The vast majority of antibody escape mutations have been associated with the S1 subunit of the spike protein, especially the Receptor Binding Domain (RBD) but also the N-terminal Domain (NTD). The other region of the spike, the S2 subunit, is the most conserved region amongst coronaviruses. We hypothesized that S2-specific antibody responses are suboptimal in vaccinated and SARS-CoV-2 infected patients resulting in an ineffective neutralization of distant coronaviruses. Here, we analyzed S2-specific antibody responses SARS-CoV-2-infected individuals, including a mixed cohort of those with and without immunosuppression and prior vaccination. We found that S2-specific antibody responses are generally lower than S1-specific antibody responses. Furthermore, we observed in immunocompetent individuals that S1 and S2-specific antibody responses are both positively correlated with Wuhan, Omicron, SARS-CoV and W1V1-CoV pseudovirus neutralization. Among the immunocompromised patients, S1-specific antibody responses were rarely correlated with pseudovirus neutralization in contrast to S2-specific antibody responses which frequently correlated with pseudovirus neutralization. These data highlight the potential of the S2-subunit as an ideal target for induction of cross-neutralizing antibody immunity against divergent coronaviruses. Competing Interests: The authors declare no competing interests. J.Z.L has consulted for Abbvie and received a grant from Merck but none of these activities impacted nor influenced the design, performance and conclusions of this study. J.A.S. has received research support from Boehringer Ingelheim and Bristol Myers Squibb unrelated to this work. He has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer, ReCor, Sobi, and UCB unrelated to this work.Additional Declarations: No competing interests reported.
Databáze:	MEDLINE
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