Cross-protective immunity following coronavirus vaccination and coronavirus infection
Tanushree Dangi, … , Justin M. Richner, Pablo Penaloza-MacMaster
Tanushree Dangi, … , Justin M. Richner, Pablo Penaloza-MacMaster
Published October 8, 2021
Citation Information: J Clin Invest. 2021;131(24):e151969. https://doi.org/10.1172/JCI151969.
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Research Article COVID-19 Vaccines

Cross-protective immunity following coronavirus vaccination and coronavirus infection

Abstract

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have shown efficacy against SARS-CoV-2, it is unknown if coronavirus vaccines can also protect against other coronaviruses that may infect humans in the future. Here, we show that coronavirus vaccines elicited cross-protective immune responses against heterologous coronaviruses. In particular, we show that a severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) vaccine developed in 2004 and known to protect against SARS-CoV-1 conferred robust heterologous protection against SARS-CoV-2 in mice. Similarly, prior coronavirus infections conferred heterologous protection against distinct coronaviruses. Cross-reactive immunity was also reported in patients with coronavirus disease 2019 (COVID-19) and in individuals who received SARS-CoV-2 vaccines, and transfer of plasma from these individuals into mice improved protection against coronavirus challenges. These findings provide the first demonstration to our knowledge that coronavirus vaccines (and prior coronavirus infections) can confer broad protection against heterologous coronaviruses and establish a rationale for universal coronavirus vaccines.

Authors

Tanushree Dangi, Nicole Palacio, Sarah Sanchez, Mincheol Park, Jacob Class, Lavanya Visvabharathy, Thomas Ciucci, Igor J. Koralnik, Justin M. Richner, Pablo Penaloza-MacMaster

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Figure 1

Cross-reactive antibody responses following SARS-CoV-2 vaccination.

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Cross-reactive antibody responses following SARS-CoV-2 vaccination. Anti...
Antibody responses after SARS-CoV-2 vaccination. (A) Participants 1–17, 24–29, and 31–47 received the Pfizer/BioNTek vaccine; participants 18–23 received the Moderna vaccine; and participant 30 received the Johnson & Johnson vaccine. Participants were determined to be unexposed (participants 1–26) prior to vaccination on the basis of a negative serology test for SARS-CoV-2 spike and nucleocapsid proteins before vaccination (0–7 days prior to vaccination). Participants 27–30 were unexposed, under immunosuppressive regimens, and did not interrupt their treatments at the time of vaccination (treatments for participant 27: azathioprine and prednisone; participant 28: anti–IL-6 monoclonal antibody; participant 29: prednisone; and participant 30: methotrexate). Exposed participants 31–47 tested positive for SARS-CoV-2 by RT-PCR prior to vaccination. SARS-CoV-2 spike–specific antibody responses after vaccination in (B) unexposed, (C) unexposed immunosuppressed, and (D) exposed participants. (E) Summary of SARS-CoV-2 spike antibody responses. SARS-CoV-1 spike–specific antibody responses after vaccination in (F) unexposed, (G) unexposed immunosuppressed, and (H) exposed participants. (I) Summary of SARS-CoV-1 spike antibody responses. OC43 spike–specific antibody responses after vaccination in (J) unexposed, (K) unexposed immunosuppressed, and (L) exposed participants. (M) Summary of OC43 spike antibody responses. The y axis indicates the endpoint titer (the highest plasma dilution at which the absorbance was greater than 2 times that of the negative controls: human pre-2019 plasma; see Methods). Data shown are from an ongoing longitudinal study, in which participants were vaccinated on different dates, hence the heterogeneity in the available time points after infection. Antibody responses were evaluated by ELISA. Dashed lines represent the LOD. In panels E, I, and M, the indicated P values compare V0 and V1 from each group by paired Wilcoxon test. ****P < 0.0001, by paired Wilcoxon test (P > 0.05, NS). All participants except participant 28 (lack of V0 data) were included in the analysis. Error bars indicate the SEM.