key: cord-1017936-uu2y5rbr
authors: Au, Wing Ying; Ye, Chengjin; Briner, Sydney Leigh; Suarez, Gianmarco Domenico; Han, Jeewon; Xu, Xinzhou; Park, Jun-Gyu; Brindley, Melinda Ann; Martinez-Sobrido, Luis; Cheung, Peter Pak-Hang
title: Systematic comparison between BNT162b2 and CoronaVac in the seroprotection against SARS-CoV-2 Alpha, Beta, Gamma, and Delta variants
date: 2022-03-02
journal: J Infect
DOI: 10.1016/j.jinf.2022.02.030
sha: 14ed1d765706afc4ca48e26bdc0294aa0ad2eb90
doc_id: 1017936
cord_uid: uu2y5rbr

nan

 Sera from BNT162b2 recipients seroprotects more than CoronaVac  While BNT162b2 seroprotect Beta less, CoronaVac protects against all variants similarly to original WA1 strain.  Antibodies elicited by CornaVac can bind to both Spike and Nucleocapsid, whereas BNT162b2 could only bind to Spike

In this Journal, Akpolat and Uzun reported data indicating reduced mortality after CoronaVac vaccination (1) . Akpolat were aged 18-44, 34 (61%) were aged 45-64, and 2 (4%) were over 65. (Table 1 ). The mean age was 47.9 (SD 11.4). Forty-five (80%) people had no medical conditions. Sera were collected at mean of 39 days after the second dose (range 21-76 days).

Using natural live viruses, the neutralizing antibody titer at 50% inhibition (NT 50 ) of mRNA vaccine sera was more seroprotective than that of inactivated virus vaccine sera ( Figure 1A ).

When tested against the original WA1 strain, BNT162b2 recipients' sera had NT 50 values 2.4fold higher (p<0.001) than CoronaVac. Our unvaccinated controls failed to register a NT 50 value as no seroprotection was observed. Additionally, we determined that the number of days between the second dose and blood collection did not correlate with NT 50 , indicating that variations in the number of days following the second dose at which blood was collected for analysis did not impact our readings. To determine if the neutralization is mainly mediated by Spike (S) protein, we used rVSV pseudoparticles ( Figure 1B) Figure 1C ). BNT162b2 sera have a 3.4-fold lower NT 50 against Beta than WA1 (p<0.001) ( Figure 1C ). We and others have previously shown that changes at E484 in Beta reduce neutralization titers of mRNA vaccines (10) . In contrast, the neutralization titers against all four variants were low and comparable to WA1 in sera from

CoronaVac-vaccinated individuals ( Figure 1C ). The three negative controls (sera from unvaccinated healthy people) did not show seroprotection against all the virus strains tested in our study.

Using an ELISA against purified Spike protein receptor-binding domain (RBD), full-length Nucleocapsid (N), and the C-terminal domain (CTD) of N, we tested the vaccinated sera for protein-specific seroneutralization (see Supplementary methods). Seropositivity to the virus targeting antigen (S RBD, full-length or CTD N) was found to be vastly different amongst the two vaccine types (p<0.001) ( Figure 1D) . In summary, we showed that CoronaVac exhibited a lower neutralization titer compared to BNT162b2 for prototype virus WA1, and all variants tested in this study (Alpha, Beta, Gamma, and Delta). The inactivated virus vaccine did not exhibit reduced neutralization titer against any of the mutants. Inactivated virus is seropositive to both Spike and Nucleocapsid proteins, whereas BNT162b2 is seropositive to Spike. This leads to a reduced neutralization efficiencies towards Beta, where a single mutation in the Spike protein is responsible for antibody escape. ELISA titers against the RBD of Spike protein can be predictive of neutralization by cVNT against not only the prototype WA1 strain, but also variants of concern. This correlation is lacking in CoronaVac. Our findings contribute to a better understanding of how antibodies bind to SARS-CoV-2 antigens.

The authors do not have a commercial or other association that might pose a conflict of interest.

This study has no funding source to report. 

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D) Serum titers of antibodies in BNT162b2-and CoronaVac-vaccinated human sera in optical density from ELISA against purified WA1 Spike RBD