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. 2004 Dec 10;325(2):445-52.
doi: 10.1016/j.bbrc.2004.10.052.

Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry

Yuxian He  1 , Yusen Zhou, Pamela Siddiqui, Shibo Jiang
Affiliations

Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry

Yuxian He et al. Biochem Biophys Res Commun. .

Abstract

The only severe acute respiratory syndrome (SARS) vaccine currently being tested in clinical trial consists of inactivated severe acute respiratory syndrome-associate coronavirus (SARS-CoV). However, limited information is available about host immune responses induced by the inactivated SARS vaccine. In this study, we demonstrated that SARS-CoV inactivated by beta-propiolactone elicited high titers of antibodies in the immunized mice and rabbits that recognize the spike (S) protein, especially the receptor-binding domain (RBD) in the S1 region. The antisera from the immunized animals efficiently bound to the RBD and blocked binding of RBD to angiotensin-converting enzyme 2, the functional receptor on the susceptible cells for SARS-CoV. With a sensitive and quantitative single-cycle infection assay using pseudovirus bearing the SARS-CoV S protein, we demonstrated that mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50% inhibitory titers of 1:7393 and 1:2060, respectively. These data suggest that the RBD of S protein is a major neutralization determinant in the inactivated SARS vaccine which can induce potent neutralizing antibodies to block SARS-CoV entry. However, caution should be taken in using the inactivated SARS-CoV as a vaccine since it may also cause harmful immune and/or inflammatory responses.

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Figures

Fig. 1
Fig. 1
Antibody responses against SARS-CoV in the immunized mice (A) and rabbits (B). Mouse and rabbit sera were tested at a series of 4-fold dilutions by commercial diagnostic ELISA kit using a mixture of proteins purified from viral lysates as coating antigens.
Fig. 2
Fig. 2
Inactivated SARS-CoV induced high titers of antibodies in mice against full-length S protein (A), S1-C9 (B), and RBD-Fc (C). Mouse sera were tested at a series of 2-fold dilutions by ELISA.
Fig. 3
Fig. 3
Inactivated SARS-CoV induced high titers of antibodies in rabbits against full-length S protein (A), S1-C9 (B), and RBD-Fc (C). Rabbit sera were tested at a series of 2-fold dilutions by ELISA.
Fig. 4
Fig. 4
Inhibition of RBD-Fc binding to ACE2 by antibodies in the mouse and rabbit antisera. (A) RBD-Fc bound to soluble ACE2 in a dose-dependant manner; mouse (B) and rabbit (C) antisera at 1:50 dilution inhibited binding of RBD-Fc to ACE2.
Fig. 5
Fig. 5
Inhibition of S protein-mediated virus entry by antibodies in the mouse antisera. (A) Infection of 293T/ACE2 cells by SARS pseudovirus was determined in the presence of preimmune and antisera at 1:100 dilution. (B) Inhibition of SARS pseudovirus infection by mouse antisera at a series of 2-fold dilutions and percentage inhibition was calculated for each sample.
Fig. 6
Fig. 6
Inhibition of S protein-mediated virus entry by antibodies in the rabbit antisera. (A) Infection of 293T/ACE2 cells by SARS pseudovirus was determined in the presence of preimmune and antisera at 1:100 dilution. (B) Inhibition of SARS pseudovirus infection by rabbit antisera at a series of 2-fold dilutions and percentage inhibition was calculated for each sample.
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