PreprintBrief ReportVersion 3Preserved in Portico This version is not peer-reviewed
Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death
Version 1
: Received: 6 July 2020 / Approved: 8 July 2020 / Online: 8 July 2020 (10:38:32 CEST)
Version 2
: Received: 2 August 2020 / Approved: 4 August 2020 / Online: 4 August 2020 (10:19:23 CEST)
Version 3
: Received: 1 September 2020 / Approved: 4 September 2020 / Online: 4 September 2020 (10:45:26 CEST)
How to cite:
Root-Bernstein, R. Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death. Preprints2020, 2020070141. https://doi.org/10.20944/preprints202007.0141.v3.
Root-Bernstein, R. Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death. Preprints 2020, 2020070141. https://doi.org/10.20944/preprints202007.0141.v3.
Cite as:
Root-Bernstein, R. Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death. Preprints2020, 2020070141. https://doi.org/10.20944/preprints202007.0141.v3.
Root-Bernstein, R. Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death. Preprints 2020, 2020070141. https://doi.org/10.20944/preprints202007.0141.v3.
Abstract
Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
4 September 2020
Commenter:
Robert Root-Bernstein
Commenter's Conflict of Interests:
Author
Comment:
Manuscript rewritten in response to comments from three reviewers. Methods explained in more detail; statistics removed; clarification of limitations of the results with regard to alternative hypothesis that protection afforded by pneumococcal vaccines might simply be due to protection agains superinfection.
Commenter: Robert Root-Bernstein
Commenter's Conflict of Interests: Author