SARS-CoV-2 Antibody Response After ChAdOx1 nCoV-19 Vaccination in Persons With Previous SARS-CoV-1 Infection

A nosocomial outbreak of severe acute respiratory syndrome (SARS) (caused by SARS-CoV-1) occurred at the Kaohsiung Chang Gung Memorial Hospital (KCGMH) in 2003.¹ Sixteen health care workers (HCWs) had SARS-CoV-1 infection.¹ In 2021, a community outbreak of SARS-CoV-2 occurred in Taiwan.² It is potentially possible that individuals with prior SARS-CoV-1 infection were protected from infection. If so, antibody levels after vaccination might be higher than in individuals who did not have SARS-CoV-1 infection. This study assessed antibody levels after ChAdOx1 nCoV-19 vaccination (AstraZeneca) in individuals with previous SARS-CoV-1 infection compared with uninfected individuals who received ChAdOx1 vaccination.

The HCWs at KCGMH who were vaccinated with ChAdOx1 participated in this study (March to July 2021). Blood samples were collected 4 weeks or longer after receipt of ChAdOx1 between June and July 2021. The HCWs with prior SARS-CoV-1 infection were identified by the KCGMH mandatory communicable disease reporting system.¹ The frontline, patient-facing HCWs at KCGMH are routinely screened for SARS-CoV-2 weekly using saliva samples by real-time reverse transcriptase–polymerase chain reaction. Total anti–SARS-CoV-2-spike protein receptor-binding domain (RBD) antibody (Roche Elecsys) levels were measured. Antinucleocapsid antibody (Roche Elecsys; predominantly immunoglobulin G) levels were ascertained (cutoff index, <1.0, for nonreactive samples) in participants with prior SARS-CoV-1 infection (eMethods in the Supplement). Significant differences between groups were tested using the Mann-Whitney U test; a 2-tailed P value of <.05 was considered significant. Statistical analysis was performed using SPSS, version 17.0 (IBM). This study was approved by the ethics committee of KCGMH, and written informed consent was obtained from all participants.

Overall, 340 participants were included (Table). Among 8 participants with prior SARS-CoV-1 infection (6 women [75%]), 7 (87.5%) received 1 dose and 1 (12.5%) received 2 doses of ChAdOx1. Of 332 participants without infection (244 women [73.5%]), 295 (88.9%) received 1 dose and 37 (11.1%) received 2 doses of ChAdOx1. During the study, 327 participants (96.2%) with available results were negative for SARS-CoV-2 real-time reverse transcriptase–polymerase chain reaction testing. To date, no HCWs at KCGMH have acquired SARS-CoV-2 infection.³ Among participants who received 1 dose of ChAdOx1, individuals with prior SARS-CoV-1 infection (median [IQR] age, 45.8 [43.9-52.6] years) were significantly older than those without infection (median [IQR] age, 36.3 [30.7-43.9] years) (P = .003). The median time from vaccination to antibody measurement among participants with prior SARS-CoV-1 infection (59 days; IQR, 56-68 days) was significantly longer than that among uninfected participants (46 days; IQR, 42-50 days) (P < .001). After 1 ChAdOx1 dose, the geometric mean of anti–SARS-CoV-2-spike RBD antibody levels were significantly higher in those with prior SARS-CoV-1 infection (4441.2 U/mL; 95% CI, 2337.8-8437.3) than in those without prior infection (65.0 U/mL; 95% CI, 59.0-71.7) (P < .001) and in uninfected individuals who had received 2 ChAdOx1 doses (517.4 U/mL; 95% CI, 383.0-699.0) (P < .001) (Figure). The geometric mean of antinucleocapsid antibody levels in the 8 participants with previous SARS-CoV-1 infection was a cutoff index of 7.1.

In this study, individuals with prior SARS-CoV-1 infection and 1 dose of ChAdOx1 had higher anti–SARS-CoV-2-spike RBD antibody levels than those without infection and either 1 or 2 doses of ChAdOx1, despite being older and having a longer interval between vaccination and antibody level measurement. The presence of antinucleocapsid antibodies in participants with previous SARS-CoV-1 infection is consistent with previous reports of cross-reactivity to SARS-CoV-2–nucleocapsid in individuals with prior SARS-CoV-1 infection, even if evaluated 18 years after the infection.^4,5

Immunological memory is the key point to gaining insights into the likelihood of the durability of protective immunity against SARS-CoV-2 infection.⁶ Accruement of a heterogeneous repertoire of memory cells is crucial for the rapid development of protective immunity following reinfection. In this article, we offer a potential proof of concept for a novel vaccine that targets SARS-CoV-1 and SARS-CoV-2 spike glycoproteins to establish durable, protective immunity against SARS-CoV-2 and other sarbecoviruses. Limitations of this study included the small sample size and lack of baseline antispike RBD and antinucleocapsid antibody measurements.

Accepted for Publication: November 14, 2021.

Published Online: January 24, 2022. doi:10.1001/jamainternmed.2021.7679

Corresponding Author: Ing-Kit Lee, MD, School of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd, Guishan District, Taoyuan City 33302, Taiwan, Republic of China (leee@cgmh.org.tw).

Author Contributions: Drs Chen and Lee had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Chen, Lu, Wang.

Acquisition, analysis, or interpretation of data: Chen, Lu, You, Lee.

Drafting of the manuscript: Chen, Lu, Lee.

Critical revision of the manuscript for important intellectual content: Lu, You, Wang, Lee.

Statistical analysis: Lu, Lee.

Obtained funding: Lu.

Administrative, technical, or material support: Lu, Wang.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by the Chang Gung Memorial Hospital (grant CORPG8L0611).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.