Messenger RNA COVID-19 vaccines induce high levels of short-lived antibodies compared to natural infection

In a recent study published on medRxiv* preprint server, researchers extensively studied the antibody dynamics induced by naturally occurring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination in the diverse population of Qatar.

Researchers found that the two-dose vaccination schedule with a messenger ribonucleic acid (COVID-19) coronavirus disease 2019 (COVID-19) vaccine increased antibody levels, albeit for a short time .

Study: Elevated but short-lived levels of anti-SARS-CoV2, IgM, IgA, and IgG neutralization in mRNA vaccinees compared to naturally infected participants. Image Credit: PIC SNIPE/Shutterstock


A mass vaccination campaign began in December 2020 in Qatar, and by February 2022 Qatar had fully vaccinated around 88% of its population over the age of 12. Despite widespread vaccination, the country experienced two waves of COVID-19 due to Alpha, Beta and Delta variants of SARS-CoV-2 between January and June 2021.

Again, there was an unprecedented increase in the number of COVID-19 cases between December 2021 and January 2022. During this period, Qatar reached a record number of new daily COVID-19 cases. Meanwhile, their public health officials realized that protecting the vaccinated as well as naïve and naturally infected population from new SARS-CoV-2 variants was tedious and needed immediate attention.

There are very few data to define an antibody titer threshold sufficient to protect an individual against SARS-CoV-2 infection. Additionally, the United States Federal Food and Drug Administration (FDA) has not approved a single serological test, which can indicate whether a person is protected against COVID-19 or not. Overall, there is little evidence for immunity induced by SARS-CoV-2 infection compared to vaccine-induced immunity.

About the study

In the present study, researchers assessed the antibody responses of the population of Qatar, focusing specifically on vaccination-naïve (VN) and naturally infected (NI) individuals. Qatar has used two FDA-approved mRNA vaccines, BNT162b2 and mRNA-1273, for its mass vaccination programs.

The 100 participants in the VN study received a two-dose regimen of either BNT162b2 or mRNA-1273. In contrast, the NI group had 40 subjects who were unvaccinated but naturally infected at least once with COVID-19. The team collected phase I blood samples from the VN group at 1.4 months and phase II samples at 5.3 months after the second dose of vaccine. For the NI group, the specimen collection points for phase I and phase II were approximately 1.7 months and 5.2 months, respectively, after contracting COVID-19.

The researchers used plasma from all study participants for serological testing. Additionally, prior to sample collection, researchers collected demographic information and all COVID-19-related information from study participants.

The team performed serological tests to determine the presence of SARS-CoV-2 neutralizing antibodies (nAbs) in the obtained samples. First, they detected nAbs with a World Health Organization (WHO) conversion factor of arbitrary unit (AU) = 3.31 IU/mL. Next, they detected antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, anti-S-RBD-immunoglobulin G (IgG). It had a WHO normalization factor of 1.15 antibody binding units (BAU)/mL. Similarly, they assessed anti-S-RBD-IgM and anti-S1-IgA levels in serum samples from individuals in the VN and NI groups.

Additionally, the team used an architect-automated chemiluminescent assay to test the samples for previous infection. The test detected SARS-CoV-2 anti-nucleoprotein (anti-N) IgG antibodies, and positive anti-N results indicated prior exposure to SARS-CoV-2. The team excluded these samples from the VN study group.

For statistics, the researchers summarized all continuous variables using geometric mean titers (GMTs) and 95% confidence intervals (CIs). They created scatterplots where the horizontal bar and error bar indicated the GMTs and 95% CIs, respectively.

Finally, the team performed the Wilcoxon rank sum test for pairwise group comparisons and Mann-Whitney U to describe variation between independent samples. They also used the Shapiro-Wilk normality test to normalize the collected data.

Study results

Compared to natural infection, mRNA vaccination elicited anti-S-RBD-IgG and anti-S1-IgA antibodies in significantly elevated amounts. In 23 weeks, this increase in antibody levels decreased two to six times. Although natural infection initially elicited anti-SARS-CoV-2 antibodies in lesser amounts, they remained stable and declined approximately one to two times 22 weeks after SARS-CoV-2 infection. Notably, the levels of anti-S1-IgA were initially three times higher in the VN group than in the NI group, i.e. phase I. However, at the end of the follow-up period, the anti-S1-IgA levels became similar in both groups.

Previous studies have obtained similar results and demonstrated that IgA antibodies dominate the early immune response to SARS-CoV-2 in unvaccinated subjects. In fact, a recent report indicated that people with IgA antibodies never get COVID-19, while people with both IgG antibodies and T cells get the infection. It should be noted that IgA antibodies directed against SARS-CoV-2 S antigens persist for approximately three months in salivary and nasal secretions. Therefore, it is important to evaluate anti-S1-IgA antibodies after vaccination, as well as IgG and IgM antibodies.


According to the authors, this is the first-ever study to comprehensively assess levels of anti-S1-IgA antibodies in vaccinated individuals, as well as levels of anti-S-RBD-IgG and anti-S1-IgA antibodies. -S-RBD-IgM. The study results demonstrated the extent of decline in each SARS-CoV-2 catch, which could help policymakers make informed decisions about vaccination strategies.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

Journal reference:

  • Haissam Abou Saleh, Bushra Abo Halawa, Salma Younes, Nadin Younes, Duaa Al-Sadeq, Farah Shurrab, Na Liu, Hamda Qotba, Nader AlDewik, Ahmed Ismail, HADI M. YASSINE, Laith J Abu-Raddad, Gheyath Nasrallah. (2022). Elevated but short-lived levels of anti-SARS-CoV2, IgM, IgA, and IgG neutralization in mRNA vaccinees compared to naturally infected participants. medRxiv. do I:

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