The neutralizing antibody response in mRNA vaccinated and boosted healthcare workers against major circulating SARS-CoV-2 Omicron subvariants

By Bhavana KunkalikarJul 27 2022Reviewed by Danielle Ellis, B.Sc.

In a recent study posted to the bioRxiv* preprint server, researchers assessed the duration of the neutralizing antibody responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid (mRNA) booster vaccination.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

Humoral immunity elicited after two doses of the SARS-CoV-2 mRNA vaccine decreases over time, while a third vaccine dose is found to increase the immunity response. Extensive research is required to understand the duration of the immunity induced by booster mRNA vaccination against coronavirus disease 2019 (COVID-19).

About the study

In the present study, researchers examined the duration of neutralizing antibody (nAb) responses against SARS-CoV-2 Omicron BA.4 and BA.5 subvariants among healthcare workers vaccinated with the mRNA booster vaccine.

The team assessed nAb titers induced against SARS-CoV-2 in a cohort of healthcare workers working in the Ohio State University Wexner Medical Center in Columbus, Ohio. The eligible participants provided serological samples every three months after receiving the second SARS-CoV-2 mRNA vaccine dose. All the healthcare workers were vaccinated with homologous vaccine courses and booster doses comprising the mRNA-1273 or BNT162b2 mRNA vaccines. The team categorized the healthcare workers into three groups: one to three months after, four to six months after, and seven to nine months after the booster dose.

Furthermore, the nAb response elicited against the predominantly circulating Omicron subvariants was estimated using a pseudotyped lentivirus neutralization assay. The team developed a virus pseudotyped with the SARS-CoV-2 D614G or Omicron BA.4 or BA.5 spike protein. The durability of the mRNA COVID-19 booster vaccine over time was estimated by analyzing the nAb titers observed against each variant after booster dose receipt. The team also examined the influence of COVID-19 breakthrough infection on immunity induced by the booster vaccine.  

Results

The study results showed that the SARS-CoV-2 Omicron BA.1, BA.2, bA.4, and BA.5 subvariants displayed a substantial decrease in the nAb titers compared to the SARS-CoV-2 D614G variant. One to three months after the booster vaccine was administered, the team noted that the nAb titers were 4.7-fold lower against BA.1, 7.6-fold lower against BA.2.12.1, and 13.4-fold lower against BA.4 and BA.5 than that for D614G. Furthermore, four to six months after the COVID-19 booster vaccination, the nAb titers were 5.6-fold lower against BA.1, 9.5-fold lower against BA.2.12.1, and 17.3-fold lower against BA.4 and BA.5 lower as compared to D614G. Moreover, seven to nine months after the booster vaccination, the nAb titers were 4.6-fold lower against BA.1, 7.0-fold lower against BA.2.12.1, and 13.4-fold lower against BA.4 and BA.5 than that for D614G.

The team also observed that the BA.2.12.1, BA.4, and BA.5 subvariants displayed lower nAb titers as compared to those against BA.1. At the one to three months time point post-booster vaccination, the nAb titers were 1.6-fold lower against BA.2.12.1 in comparison to that against BA.1 and 2.9-fold lower against BA.4 and BA.5 as compared to BA.1. The team noted no remarkable differences for nAb titers among healthcare workers vaccinated with mRNA-1273 or BNT162b2 vaccines.

Furthermore, the team found that the strength of viral neutralization declined over time against all the variants, with a reduction from 2.3- to 2.5-fold from one to three months to seven to nine months after booster vaccination. The reduction in nAb titers per 30 days was 15.3% against D614G, 13.5% against BA.1, 11.1% against BA.2.12.2.1, and 12.3% against BA.4 and BA.5, respectively.

Among the healthcare workers who reported a breakthrough infection, nAb titers were found to be 2.6-fold higher one to three, four to six, and seven to nine months after booster vaccination. Interestingly, SARS-CoV-2-positive healthcare workers displayed increased nAb titers against Omicron subvariants at the four to six as well as seven to nine month time points. This suggested that breakthrough infection increased the extent of nAb response against COVID-19. Furthermore, healthcare workers who did not experience a breakthrough infection displayed reduced nAb titers over time, while those with a history of a breakthrough infection had higher nAb titers.

Conclusion

Overall, the study findings showed that the durability of immunity elicited by COVID-19 mRNA booster vaccination reduced over time. However, this decline was to a lesser extent as compared to that after the administration of two vaccine doses.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources