COVID-19 vaccine boosters to stop SARS-CoV-2-related outbreaks in healthy adults.

The unprecedented coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a threat to global health since it was first announced on March 11, 2020. Since then the United States has rolled out two-dose regimens of the BNT162b2/Pfizer and mRNA-1273/Mod messenger ribonucleic acids (mRNA) vaccines against SARS-CoV-2 by December 2020. Both vaccines protect against COVID-19-related hospitalization and death for at least six month.

Study: Antibody titers before and after booster doses of the mRNA vaccine SARS-CoV-2 in healthy adults. Image Credit: Tobias Arhelger /

The transmission of the SARS-CoV-2 B.1.617.2 (Delta) variant increased due to the weakening immunity, which resulted in a higher percentage of COVID-19 cases in the summer of 2021. The rapid increase in infection resulted in the approval by the U.S. of booster vaccines for high-risk individuals.

Since then, serological studies have revealed that there is an increase in antibody response after the first to the second dose of the mRNA vaccines. The duration and extent of the antibody response to booster doses of mRNA vaccinations after six months of complete vaccination aren’t determined.

Understanding the immune responses to COVID-19 boosters

In a recent study published on the medRxiv* preprint server, researchers measured anti-receptor-binding domain (RBD) immunoglobulin G (IgG) and surrogate virus neutralization of the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme (ACE2) receptor, before and after vaccination with boosters in 33 healthy adults. Participants were asked to sign an e-consent consent form and complete online surveys regarding their COVID-19 history and vaccination status.

Participants provided fingerstick dried blood spot samples prior to booster administration and 6 and 10 days following booster vaccination. The results of the study were compared to results from a prior study using the same protocol.

The antibody responses to SARS-CoV-2 infection were measured in the previous community-based study. Participants were classified as seropositive or seronegative , based on the presence of anti-RBD IgG antibodies prior to vaccination.

Research findings

The study data showed that antibody responses after receiving the booster dose were more than natural infection with SARS/CoV-2 after two doses the vaccine as well as after both vaccination and natural infection. In addition, post-booster IgG levels were higher in females as in comparison to males and negatively correlated with age.

Additionally further, the SARS-CoV-2 Delta variant showed high surrogate neutralization; however the neutralization response was still lower than that following exposure to the wild-type SARS-CoV-2 strain. No differences were observed for neutralization of the SARS-CoV-2 Delta variant in males and females. However the inhibitory level of 50 percent (IC50) was associated negatively with age.

A) Response to COVID-19 booster mRNA vaccination was determined as anti-RBD IgG antibody levels in dried blood spots. The median IgG concentration (black dashed lines) increased from 4.4ug/ml prior to booster to 101.6ug/ml after booster (*p0.001). The grey dots represent samples that were paired. n=33. B) There was a median 25-fold change post-booster. C) Median IgG anti-RBD concentration (black dashed lines) are displayed. Outpatient COVID-19 patients had a median of 1.92 Ug/ml (n=76), 14-42 days after the onset of infection. Patients with COVID-19 following vaccination had a higher average (60.61 Ug/ml, N=73, 542 days after the 2nd dose). People who had not been exposed to COVID-19 but were not seropositive or positive and then vaccinated using a 2-dose vaccination had a median IgG of 34.15ug/ml, (n=181) and 33.09ug/ml, (n=687). Pre-booster levels mean 237.9 days after two doses of vaccine were 4.4 mg/ml (n=33) as compared to post-booster vaccination level of 101.6 ug/ml (n=33). The 25 th percentiles and the 75 _th percentiles are shown by dots. (*p<0.001).


The results indicated that the administration of the BNT162b2/Pfizer or mRNA-1273/Moderna boosters may stop the spread of infections through the development of large antibodies in healthy adults. Additionally, the antibody-mediated immunity could last for a longer duration as opposed to the one produced after the second vaccine dose.

Certain limitations associated with the study include a limited time frame, small sample size, and the absence of cellular immune measures. Future studies could further study the effects of boosters on the cell-mediated immune system.

“These data support boosters’ use to prevent breakthrough infections and suggest that the immune system mediated by antibodies could last longer than the second vaccine dose.”

*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:

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Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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