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AuthorZedan, Hadeel T.
AuthorSmatti, Maria K.
AuthorAl-Sadeq, Duaa W.
AuthorAl Khatib, Hebah A.
AuthorNicolai, Eleonora
AuthorPieri, Massimo
AuthorBernardini, Sergio
AuthorHssain, Ali Ait
AuthorTaleb, Sara
AuthorQotba, Hamda
AuthorIssa, Khodr
AuthorAbu Raddad, Laith J.
AuthorAlthani, Asmaa A.
AuthorNasrallah, Gheyath K.
AuthorYassine, Hadi M.
Available date2024-05-26T05:01:48Z
Publication Date2024
Publication NameJournal of Medical Virology
Identifierhttp://dx.doi.org/10.1002/jmv.29527
CitationZedan HT, Smatti MK, Al-Sadeq DW, et al. SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines. J Med Virol. 2024; 96:e29527. doi:10.1002/jmv.29527
ISSN01466615
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85188494128&origin=inward
URIhttp://hdl.handle.net/10576/55351
AbstractNeutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.
SponsorWe thank the virology research center at the National Institute of Health (VRC-NIH) for providing the plasmids used to generate SARS-CoV-2 pseudoviruses and for providing HEK293T cells. We also thank the UREP students who assisted in the blood samples collection and coordination: Tala Jamaleddin, Huda Abdul Hameed, Amira Elsharafi, Fatima AlHamaydeh, Bushra Abu Halawa, Hadiya Khalid, Nasrin Cusman, Maram Ali, Hamas Fouda, Salma Mohamud, and Reham Kamal. This study was supported by partial funds from grant #NPRP11S-1212-170092 awarded to Dr. Yassine. GKN would like to acknowledge that this work was made possible by WHO grant number COVID-19-22-43; QUCG-BRC-23/24-170, and grant number UREP29-026-3-004 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the authors' responsibility.
Languageen
PublisherWiley
SubjectADCC
COVID-19
COVID-19 vaccines
humoral responses
neutralizing antibodies
NK cells
SARS-CoV-2
TitleSARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines
TypeArticle
Issue Number3
Volume Number96
ESSN1096-9071
dc.accessType Open Access


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