TY - JOUR
T1 - Comparative analysis of the neutralizing activity against SARS-CoV-2 Wuhan-Hu-1 strain and variants of concern
T2 - Performance evaluation of a pseudovirus-based neutralization assay
AU - D’Apice, Luciana
AU - Trovato, Maria
AU - Gramigna, Giulia
AU - Colavita, Francesca
AU - Francalancia, Massimo
AU - Matusali, Giulia
AU - Meschi, Silvia
AU - Lapa, Daniele
AU - Bettini, Aurora
AU - Mizzoni, Klizia
AU - Aurisicchio, Luigi
AU - Di Caro, Antonino
AU - Castilletti, Concetta
AU - De Berardinis, Piergiuseppe
N1 - Funding Information:
This study was supported by funds to the Istituto Nazionale per le Malattie Infettive (INMI) Lazzaro Spallanzani IRCCS, Rome (Italy), from Ministero della Salute (Ricerca Corrente - linea 1); the European Commission – Horizon 2020 (EU project 101003544 – CoNVat; EU project 101005075-KRONO) the European Virus Archive – GLOBAL (grants no. 653316 and no. 871029), and by funds from PON 2014-2020 “TITAN – Nanotecnologieper l’immunoterapia dei tumori” to CNR.
Publisher Copyright:
Copyright © 2022 D’Apice, Trovato, Gramigna, Colavita, Francalancia, Matusali, Meschi, Lapa, Bettini, Mizzoni, Aurisicchio, Di Caro, Castilletti and De Berardinis.
PY - 2022/9/26
Y1 - 2022/9/26
N2 - Objectives: Emergence of new variants of SARS-CoV-2 might affect vaccine efficacy. Therefore, assessing the capacity of sera to neutralize variants of concern (VOCs) in BSL-2 conditions will help evaluating the immune status of population following vaccination or infection. Methods: Pseudotyped viruses bearing SARS-CoV-2 spike protein from Wuhan-Hu-1/D614G strains (wild type, WT), B.1.617.2 (Delta), or B.1.1.529 (Omicron) VOCs were generated to assess the neutralizing antibodies (nAbs) activity by a pseudovirus-based neutralization assay (PVNA). PVNA performance was assessed in comparison to the micro-neutralization test (MNT) based on live viruses. Sera collected from COVID-19 convalescents and vaccinees receiving mRNA (BNT16b2 or mRNA-1273) or viral vector (AZD1222 or Ad26.COV2.S) vaccines were used to measure nAbs elicited by two-dose BNT16b2, mRNA-1273, AZD1222 or one-dose Ad26.CO2.S, at different times from completed vaccination, ~ 1.5 month and ~ 4-6 months. Sera from pre-pandemic and unvaccinated individuals were analyzed as controls. Neutralizing activity following booster vaccinations against VOCs was also determined. Results: PVNA titers correlated with the gold standard MNT assay, validating the reliability of PVNA. Sera analyzed late from the second dose showed a reduced neutralization activity compared to sera collected earlier. Ad26.CO2.S vaccination led to very low or absent nAbs. Neutralization of Delta and Omicron BA.1 VOCs showed significant reduction of nAbs respect to WT strain. Importantly, booster doses enhanced Omicron BA.1 nAbs, with persistent levels at 3 months from boosting. Conclusions: PVNA is a reliable tool for assessing anti-SARS-CoV-2 nAbs helping the establishment of a correlate of protection and the management of vaccination strategies.
AB - Objectives: Emergence of new variants of SARS-CoV-2 might affect vaccine efficacy. Therefore, assessing the capacity of sera to neutralize variants of concern (VOCs) in BSL-2 conditions will help evaluating the immune status of population following vaccination or infection. Methods: Pseudotyped viruses bearing SARS-CoV-2 spike protein from Wuhan-Hu-1/D614G strains (wild type, WT), B.1.617.2 (Delta), or B.1.1.529 (Omicron) VOCs were generated to assess the neutralizing antibodies (nAbs) activity by a pseudovirus-based neutralization assay (PVNA). PVNA performance was assessed in comparison to the micro-neutralization test (MNT) based on live viruses. Sera collected from COVID-19 convalescents and vaccinees receiving mRNA (BNT16b2 or mRNA-1273) or viral vector (AZD1222 or Ad26.COV2.S) vaccines were used to measure nAbs elicited by two-dose BNT16b2, mRNA-1273, AZD1222 or one-dose Ad26.CO2.S, at different times from completed vaccination, ~ 1.5 month and ~ 4-6 months. Sera from pre-pandemic and unvaccinated individuals were analyzed as controls. Neutralizing activity following booster vaccinations against VOCs was also determined. Results: PVNA titers correlated with the gold standard MNT assay, validating the reliability of PVNA. Sera analyzed late from the second dose showed a reduced neutralization activity compared to sera collected earlier. Ad26.CO2.S vaccination led to very low or absent nAbs. Neutralization of Delta and Omicron BA.1 VOCs showed significant reduction of nAbs respect to WT strain. Importantly, booster doses enhanced Omicron BA.1 nAbs, with persistent levels at 3 months from boosting. Conclusions: PVNA is a reliable tool for assessing anti-SARS-CoV-2 nAbs helping the establishment of a correlate of protection and the management of vaccination strategies.
KW - COVID-19
KW - immunogenicity
KW - neutralization assay
KW - neutralizing antibodies
KW - pseudotyped virus
KW - SARS-CoV-2
KW - vaccines
KW - variants of concern
UR - http://www.scopus.com/inward/record.url?scp=85139785194&partnerID=8YFLogxK
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U2 - 10.3389/fimmu.2022.981693
DO - 10.3389/fimmu.2022.981693
M3 - Article
C2 - 36225911
AN - SCOPUS:85139785194
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 981693
ER -