Several studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines produce higher levels of antibodies compared to SARS-CoV-2 infections in most individuals. However, the specificities of antibodies induced by infections vs. vaccination are poorly understood.
Study: SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations
Studying the magnitude and specificity of SARS-CoV-2 antibodies elicited by SARS-CoV-2 vaccination and infection
Researchers from the US recently characterized the scale and specificity of SARS-CoV-2 spike-reactive antibodies from 23 participants who received SARS-CoV-2 mRNA vaccines and 10 acutely infected health care workers. They found that primary mRNA vaccination and infection elicited S1- and S2-reactive antibodies, while secondary mRNA vaccination elicited mostly S1 antibodies. This study is available on the medRxiv* preprint server.
Magnetic bead-based absorption assays showed that SARS-CoV-2 infections produced a large proportion of original antigenic sin-like antibodies that can bind efficiently to seasonal human coronaviruses but bind poorly to SARS-CoV-2. On the other hand, mRNA vaccinations produced modestly reactive antibodies to other seasonal human coronaviruses but highly reactive to SARS-CoV-2. Overall, the data from the study indicates that mRNA vaccinations elicit different antibody responses compared to those induced by SARS-CoV-2 infections.
SARS-CoV-2 mRNA vaccines elicit more polyclonal antibodies compared to SARS-CoV-2 infections
According to the authors, the study's findings are consistent with previous reports indicating that mRNA vaccinations elicit more diverse and broader antibody responses that can neutralize SARS-CoV-2 variants more effectively than the antibodies elicited SARS-CoV-2 infection.
Specificity of SARS-CoV-2 antibodies induced after SARS-CoV-2 infection versus vaccination. ELISAs were completed to quantify levels of serum antibodies binding to the SARS-CoV-2 full-length spike (FL-S) protein, the S1 domain (S1) of S, and the S2 domain (S2) of S after SARS-CoV-2 infection (A) and mRNA vaccination (B). Paired t-tests of log2 transformed antibody titers ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05. We calculated fold-change in antibody titers before and after seroconversion and pre-/post-prime and boost doses of a SARS-CoV-2 mRNA vaccine (C-E). One way ANOVA of antibody fold change ****p<0.0001, **p<0.01 *p<0.05. Horizontal lines indicate geometric mean and error bars represent standard deviation.
The findings clearly show that mRNA vaccines elicit higher magnitudes of polyclonal antibodies and have different specificities than those produced by SARS-CoV-2 infections. The data also demonstrate that while primary vaccinations produce antibodies that bind to the S1 and S2 subunits of the spike protein, second vaccine doses produce S1-specific antibody responses.
"Here, we found that polyclonal antibodies elicited by SARS-CoV-2 mRNA vaccines are at a higher magnitude and have different specificities compared to those elicited by SARS-CoV-2 infections."
The study also found significant differences in OC43 spike binding between antibodies elicited by SARS-CoV-2 mRNA vaccinations vs. infections. Although SARS-CoV-2 infections produced more antibodies that bound to the S2 subunit of the OC43 spike protein, absorption assays showed that these antibodies could not bind efficiently to the SARS-CoV-2 spike protein.
SARS-CoV-2 infections and vaccinations might recall memory B cells elicited by prior β-hCoV infections
The authors mentioned that further studies are required to better understand mechanisms underlying different antibody responses elicited by SARS-CoV-2 vaccinations vs. infections. One possibility is that SARS-CoV-2 infections and vaccinations recall memory B cells elicited by prior β-hCoV infections, and long-lasting germinal centers elicited by mRNA vaccinations are essential to allow somatic hypermutations that can boost the formation of cross-reactive S2 antibodies that can bind efficiently to the spike proteins of both SARS-CoV-2 and β-hCoVs.
"Unlike antibodies elicited by infections, these vaccine-elicited antibodies were truly cross-reactive and bound efficiently to both SARS-CoV-2 and OC43 spike proteins."
Recall of antibodies elicited by past infections may compromise production of new SARS-CoV-2 antibodies in severe COVID-19
According to the authors, the production of OC43 S2-reactive antibodies after SARS-CoV-2 infection is consistent with Thomas Francis' doctrine of 'original antigenic sin'. Francis' findings showed that antibodies elicited by influenza vaccines bound strongly to influenza virus strains individuals were exposed to in childhood. However, it is not clear if the recall of past antibody responses occurs at the expense of producing new antibodies.
"The functional consequences of recalling low-affinity S2-reactive antibodies following SARS163 CoV-2 infections are unclear."
Although the authors' previous studies found no correlation between OC43-reactive antibody induction and outcome of disease following SARS-CoV-2 infection, a recent study suggested that OC43-reactive antibodies' recall is associated with compromised production of new SARS-CoV-2 antibodies in individuals with severe COVID-19.
"Further studies are required to determine how the induction of different types of hCoV and SARS-CoV-2 antibodies affect disease outcome following SARS-CoV-2 infections."
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations Elizabeth M. Anderson, Theresa Eilola, Eileen Goodwin, Marcus J. Bolton, Sigrid Gouma, Rishi R. Goel, Mark M. Painter, Sokratis A. Apostolidis, Divij Mathew, Debora Dunbar, Danielle Fiore, Amanda Brock, JoEllen Weaver, John S. Millar, Stephanie DerOhannessian, The UPenn COVID Processing Unit, Allison R. Greenplate, Ian Frank, Daniel J. Rader, E. John Wherry, Scott E. Hensley, medRxiv, 2021.09.30.21264363; doi: https://doi.org/10.1101/2021.09.30.21264363, https://www.medrxiv.org/content/10.1101/2021.09.30.21264363v1