Prediction of waning COVID-19 vaccine efficacy against Omicron variant

In a recent study posted to the medRxiv* preprint server, a team of researchers performed a meta-analysis of the results of four previous studies estimating fold-drop in neutralization titer against Omicron to present a combined estimate of the same. In addition, they estimated the protection conferred by the previous infection with ancestral severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) strain vis-a-vis symptomatic and severe Omicron infection.

Study: Analysis: A meta-analysis of Early Results to predict Vaccine efficacy against Omicron. Image Credit: Viacheslav Lopatin/Shutterstock

Omicron (B.1.1.529), declared a variant of concern (VOC) by the World Health Organization in November 2021, is known for escaping the host’s natural immune responses and most of the available vaccines due to the mutations in its spike (S) protein. Since December 2021, four laboratories have reported the estimates of a drop in neutralization titer against Omicron in the range of 2- to over 20-fold.

Several previous large meta-analyses of the neutralization of other SARS-CoV-2 VOCs have shown that the drop in neutralization against a variant varies dramatically between laboratories and assays. The results also depend on the limit of detection of the assay and the potency of the serum. The authors of this study aggregated a range of estimates from multiple laboratory reports rather than relying on a single laboratory result.

About the study

In this study, the researchers collated data from four previous studies. They presented a combined estimate of the fold-drop in neutralization titer against Omicron after accounting for the laboratory and censoring effects of neutralization titers below the detection limit. Vaccine efficacy against that VOC could also be determined once the loss of neutralization titer against a novel VOC is known. Therefore, the researchers used a previously developed method for estimating vaccine efficacy based on neutralization titers. They predicted vaccine efficacy against Omicron shortly after vaccination, six months later, and the impact of a booster dose of mRNA vaccine.

Results

The study results showed a combined estimate of the drop in neutralization titer against Omicron of 9.7-fold. In addition, the results showed that prior infection from an ancestral SARS-CoV-2 strain conferred 34.3% protection against symptomatic Omicron infection and 76.6% protection in severe cases. 

Consistent with the results of previous research studies, the researchers observed that following primary vaccination, the protection conferred by the ChAdOx1 nCoV-19 vaccine was similar to the protection given by prior infection, but the mRNA vaccines conferred higher protection. However, six months after primary immunization with an mRNA vaccine, vaccine efficacy against Omicron waned to around 40% for symptomatic and 80% for severe disease cases, which increased to 86.2% after a booster dose.

Conclusions 

Overall, the study results suggest that the Omicron variant can escape natural and vaccine-induced immunity. However, it is still possible to achieve high levels of protection to symptomatic and severe infection from Omicron by boosting doses with existing vaccine dosage that target SARS-CoV-2 S protein. The vaccine efficacy estimates of this study were compared with the data from test-negative case-control study published by UK Health Security Agency as both were in good agreement. This further validated the findings of this study in the context of vaccine efficacy.

*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.