SARS-CoV-2 mRNA vaccines elicit higher levels of antibodies compared to natural infection

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
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.
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."

*Important Notice

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.

Journal reference:
  • 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
Susha Cheriyedath

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Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.

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Comments

  1. Allen Dilliplane Allen Dilliplane United States says:

    Such an awful and biased article, but unsurprising since the competing interest statement shows that one of the researchers has received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this report.

    Article highlights that fail to address the positives of the alternatives:
    1. "SARS-CoV-2 mRNA vaccines elicit higher levels of antibodies compared to SARS-CoV-2 infections"

    That's only true when you compare spike protein antibodies. How this is worded, though, is false. Spike proteins elicited by prior infection only account for a fraction (~15%) of the variety of antibodies elicited overall. This does not account for all the other types of antibodies elicited for the E, M, or, N proteins, ORF's, or NSP's.

    2. "The first dose of an mRNA vaccine generates both S1 and S2 responses while the second dose boosts primarily S1-specific antibodies"

    The S1 domain is where the majority of mutations occur, so why is this a good thing?

    3. "SARS-CoV-2 infections, but not mRNA vaccinations, elicit high levels of antibodies that bind strongly to seasonal coronaviruses but weakly to SARS-CoV-2".

    Again, they are only assessing the infection elicited antibodies for the spike protein and not comparing all the other antibodies.

    Articles like this contribute to misinformation and mistrust because they are intentionally dishonest. Vaccine development and testing traditionally uses antibody responses to infection as the baseline to compare antibodies elicited by the vaccine. This switch to using the vaccine as a baseline is going to shoot us in the foot. There are more vaccine breakthrough cases in Michigan than there are confirmed reinfection cases in the world. Properly recognizing prior infection immunity is what will get us out of this mess.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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