Effects of mRNA-Based Vaccines on Antibody Responses in Patients With and Without Prior SARS-CoV-2 Infection

Vial of mRNA vaccine and white glove.
Front view of cropped hand wearing surgical gloves and holding mRNA vaccine multidose vial for HIV (We look forward to seeing this coming into being)
Researchers conducted a study to assess the effects of mRNA-based COVID-19 vaccines on neutralizing antibody responses among patients with and without a history of SARS-CoV-2 infection.

After vaccination with an mRNA-based vaccine, individuals with no history of SARS-CoV-2 infection were found to have increased plasma neutralizing activity; however, they may not produce as potent of antibodies compared with vaccinated convalescent individuals. These findings were published in Nature.

A total of 30 patients with no history of SARS-CoV-2 infection who had received either the Moderna (n=8) or Pfizer BioNTech (n=24) COVID-19 vaccine were enrolled and matched with individuals who had recovered from a previous SARS-CoV-2 infection (convalescent group). At 2.5 weeks after the first vaccine dose and 35.5 days and 5 months after the second dose, patients with no prior SARS-CoV-2 infection were assessed for antibody responses. Patients in the convalescent group were assessed for antibody responses at 38.5 days and 5 months after vaccination.

Among patients included in the study, the median was 34.5 (range, 23-78) years and 53% were men.

Between the first and second doses of vaccine, plasma immunoglobulin (Ig)G responses to the receptor binding domain (RBD) of the SARS-CoV-2 virus were significantly increased (P <.0001); however, a 4.3-fold decrease was observed at month 5 (P <.0001).

After stratification by infection status, patients with no history of SARS-CoV-2 infection tended to have variable neutralizing activity, with a mean half-maximal neutralizing titer of 171.

Compared with patients in the convalescent group, those with no history SARS-CoV-2 infection had a 4.9- and 3.6-fold increase in neutralizing titers at 1.3 and 5 months after receiving the second vaccine dose (P <.0001), respectively.

The researchers assessed memory B cells via flow cytometry for RBD expression of the wild-type (WT) virus and 3 SARS-CoV-2 variants of concern. After the first vaccine dose, memory B cells for the WT virus were detected among all vaccinated patients, which increased at month 5. Of note, IgM-expressing memory B cells were found in 23% of blood sample specimens after the first vaccine dose but were nearly absent after the second dose. A similar pattern was observed for RBD-specific plasmablasts.

A total of 458 antibodies were tested for neutralizing capacity, 94% of which bound to the WT virus. The researchers observed that the neutralizing capacity increased between the first and second vaccine doses, mostly due to memory B cells. After the second vaccine dose, there was no improvement in the neutralizing capacity of monoclonal antibodies among patients with no history of infection (P >.99). Among patients in the convalescent group who received the second vaccine dose, memory B cell antibodies persisted up to 1 year (P =.003).

A minority of antibodies (19%) obtained from patients with no history of SARS-CoV-2 infection had potency against mutant combinations compared with 59% of antibodies among those in the convalescent group (P <.0001). For the Delta variant specifically, the vaccinated and convalescent antibodies had potencies of 21% and 69% (P =.007), respectively.

This study was limited by its small sample size and the imbalance between vaccine types.

The researchers found that mRNA-based COVID 19 vaccines conferred similar plasma neutralizing activity among patients with no history of SARS-CoV-2 vs those in the convalescent group. “Given the current rapid emergence of SARS-CoV-2 variants, boosting to prevent infection would likely be needed on a time scale of months,” the researchers concluded.

Disclosure: One author declared affiliations with industry. Please see the original reference for a full list of disclosures.


Cho A, Muecksch F, Schaefer-Babajew D, et al. Anti-SARS-CoV-2 receptor binding domain antibody evolution after mRNA vaccination. Nature. Published online October 7, 2021. doi:10.1038/s41586-021-04060-7