Exploring the comparative efficacy of booster vaccines against SARS-CoV-2 Omicron and Delta variants

A recent study posted to the medRxiv* preprint server assessed the effectiveness of vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and Delta variants.

Since the emergence of the SARS-CoV-2 Omicron variant in November 2021, global coronavirus disease 2019 (COVID-19) infections have sharply increased at an unprecedented rate. This novel variant, classified as a variant of concern (VOC) by the World Health Organization (WHO), contains over 30 mutations that impart increased transmissibility and immune-evasive traits.

Omicron vaccine breakthrough cases and reinfections have been observed in many countries raising concerns over the efficacy of available vaccines and therapeutics against the new variant. Studies have reported reduced efficacy of the BNT162b2, mRNA-1273, and ChAdOx1 vaccines against the Omicron variant; however, boosting the immune responses with an additional vaccine dose increased neutralization.

The study

In the present study, the authors measured the efficacy of primary and booster vaccinations against the SARS-CoV-2 Omicron and Delta VOCs and compared the cycle threshold (Ct) values for the two variants in infected cases according to the vaccination status.

The study was conducted in Portugal between December 6 and 26, 2021, when the Delta VOC was predominant in circulation and was gradually replaced by the Omicron VOC. The study population included Portuguese residents aged 12 years or older without a history of COVID-19 infection. People over 50 were included for assessing the effect of booster shots because the younger population was ineligible for boosters.

The Omicron variant is detected based on an S-gene target failure (SGTF) signal in reverse transcription-polymerase chain reaction (RT-PCR) tests due to the Δ69-70 deletion in its spike protein that differentiates it from the Delta VOC. The authors identified Omicron infections by whole genome sequencing (WGS) and/or by SGTF, and all SGTF-positive samples were considered as Delta variants.

In Portugal, two-dose vaccines like BNT162b2, mRNA-1273, ChAdOx1, and Janssen’s single-dose vaccine are used for primary vaccination, and BNT162b2 and mRNA-1273 vaccines are used for booster doses. The vaccination status of the infected cases was stratified as 1) unvaccinated, 2) partial primary vaccination where the COVID-19 diagnosis (vaccine breakthrough infection) was confirmed within 14 days of completion of the vaccine course (two-dose or single-dose), 3) complete primary vaccination with COVID-19 diagnosis after 14 days of the vaccine course, 4) partial boost where vaccine-boosted people were infected with COVID-19 in less than 14 days, and 5) complete boost where the COVID-19 infection was diagnosed after 14 days of administering the booster.

A chi-square test was used to compare the patient characteristics of the Omicron and Delta infections and a logistic regression analysis was used to measure confounding-adjusted odds of complete/booster vaccination. Odds ratio (OR) was calculated and an OR value of 1 indicated no difference in the odds of vaccination, an OR < 1 meant comparatively higher vaccine efficacy against the Omicron VOC than the Delta VOC, and an OR value > 1 is indicative of lower vaccination efficacy against the Omicron variant as compared to the Delta variant.

Findings

A total of 13,134 out of 15,001 collected samples were examined with Omicron cases representing 37.3% of the samples. The authors observed an OR value of 2.1 for mRNA and viral-vectored vaccines in the study population indicating lower vaccine efficacy against the Omicron variant. Around 3,737 of the participants had received booster shots and a higher OR value of 5.2 was observed for boosted individuals infected with the Omicron variant, suggesting lower effectiveness of the booster shots against Omicron compared to the Delta variant.

The researchers estimated the efficacy of vaccines against Omicron infection to be 28.1% for primary vaccination and 68.8% for the booster dose. The mean Ct value for Omicron cases ranged from 18.3 to 18.6 for different vaccines while it was between 17.8 to 19.5 for Delta infections, and these observed differences were not statistically significant.

Conclusions

Based on the above observations, the authors concluded that primary vaccination offered lower protection against the Omicron variant but the vaccine efficacy against the Omicron VOC increased after a booster shot. It is unclear whether the immunity offered by a booster could wane over time as has been observed for primary vaccination and more research is required to monitor the immune responses after the booster dose. The differences noted for Ct values between Delta and Omicron cases were not significant suggesting that the molecular basis for high transmission of Omicron was due to its mutational pattern rather than higher viral load.

To summarize, the study findings revealed that protection by primary or booster vaccination was lower against the Omicron variant as compared to the Delta variant; nonetheless, booster doses offered higher protection than primary vaccination alone. Therefore, in regions where Omicron cases are dominant, booster vaccine doses could help lower the number of COVID-19 infections and reduce the clinical severity of the disease.

*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

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.