A model-based approach to estimate vaccine efficacy against SARS-CoV-2 variants of concern

In a recent study published in Nature Communication, a group of researchers examined

the effectiveness of updated vaccines and variant-matched boosters against the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their potential to reduce hospitalizations and deaths over one year.

Study: Estimation of long-term vaccine efficacy against SARS-CoV-2 variants: a model-based approach. Image Credit: BaLLLunLa/Shutterstock.com

Background

The rapid development and distribution of SARS-CoV-2 vaccines has significantly reduced coronavirus disease 2019 (COVID-19) cases, hospitalizations and deaths worldwide.

However, the emergence of variants of concern has diminished the effectiveness of vaccines in preventing infection and transmission, although they still offer protection against serious consequences.

The Omicron variant and its subtypes became dominant, causing repeated infections due to waning immunity. New bivalent vaccines targeting Omicron have shown higher immunogenicity.

As the virus evolves, estimate the number of vaccines efficiency becomes difficult, and decisions about new vaccines and recalls will be based on immunogenicity and safety data rather than clinical trials.

About the study

The present study used empirical data on vaccine efficacy against mild illness, hospitalizations and deaths caused by Delta and Omicron BA.1/BA.2 variants of SARS-CoV-2 in England. The data included three vaccines: Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273.

For the main analysis, the authors used data from all age groups from studies as well as data for the age group > 65 years. However, there was no sex or gender stratification in the original studies, and data on prior infection were not available, which could bias estimates of vaccine effectiveness.

The immunological model used a biphasic exponential decay function to represent the immunity (IL) levels of the individual after vaccination. A logistic relationship was considered between IL and vaccine efficacy for mild illness, hospitalization and death.

Additionally, the authors explored two approaches to incorporate the impact of the third and fourth vaccine doses. Their primary analysis considered a vaccine-specific restoration of IL to a fixed, dose-dependent level after each dose, regardless of previous decay.

The IL achieved at the third and subsequent doses was also independent of the vaccine regimen used for the initial doses. As an alternative exploration, they considered a vaccine- and dose-dependent IL boost, restoring IL after the third and subsequent doses depending on the magnitude of the boost and the IL achieved after dose 2.

This approach related the IL achieved at subsequent doses to the vaccine regimen used for the main course, but not to the time elapsed since dose 2.

The study used estimates of relative neutralization titers reported in other studies to project the efficacy of the variant-matched vaccine. This was used to estimate the potential benefit of variant-adapted vaccines over ancestral vaccines.

Study results

The results of the present study revealed that the immunological model fits well with vaccine efficacy data observed for three vaccines used in England and accurately reproduces the decline in efficacy against the two Omicron variants over one year.

The estimated reduction in immune level against the Omicron variant compared to Delta is 5.1 times. Applying reductions estimated from immunogenicity data to the inferred relationship against Wuhan virus predicts more pessimistic vaccine efficacy against both variants than does direct model fitting.

According to the authors’ findings, mRNA-1273 displayed the highest immune response when comparing three vaccines, followed by BNT162b2 and then AZD1222. The study also found that the initial period immune level decline has a half-life of 35 days, while the later decline has an estimated half-life of 581 days.

Short-term projections of vaccine efficacy against the Omicron variant indicated that 180 days after the third dose, efficacy against hospitalization decreased to 49.7% for AZD1222, 70.3% for mRNA-1273, and 64.1% for BNT162b2.

One year after vaccination, predicted levels of protection further declined to 38.0% for AZD1222, 59.5% for mRNA-1273, and 52.6% for BNT162b2, providing relatively low protection against infection or mild illness and moderate protection against hospitalization.

The study also explored the potential benefit of variant-matched vaccines. Variant-adapted vaccines are believed to provide more durable protection over time against mild illness and hospitalization compared to administration of the ancestral vaccine as a fourth dose.

Discussion

As the world grapples with the endemic circulation of SARS-CoV-2, understanding the effectiveness of the COVID-19 vaccine against different variants becomes crucial.

This study presents a modeling framework that integrates knowledge about the utility of neutralizing antibody (NAT) titers as a measure of protection with population-based vaccine effectiveness data.

The model allows short-term projections of vaccine effectiveness beyond the observed time period, facilitating ongoing vaccination strategies and recall decisions for high-risk populations. However, challenges remain due to the complexity of developing immunity against the virus and its variants.

The study shows that while ancestral vaccines provide high initial protection, their effectiveness declines over time due to waning immunity and immune evasion by the Omicron variant. Switching to variant-adapted vaccines as a fourth dose can prevent nearly double the cases of severe disease over a year compared to using the ancestral vaccine for the fourth dose.

The study highlights the importance of regular booster vaccinations in the management of COVID-19, especially for vulnerable populations.

As SARS-CoV-2 continues to evolve, validated models estimating the efficacy of modified vaccines based on immunogenicity data will be essential to assess the benefit of additional doses with existing or variant-modified vaccines.

conclusion

The study presents a model that incorporates population-based and NAT vaccine efficacy data to project short-term vaccine efficacy. Heritage vaccines provide high initial protection but decline over time due to Omicron immune evasion.

As a fourth dose, variant-matched vaccines can prevent twice as many severe cases over a year. Regular booster vaccinations are essential to manage COVID-19, especially for vulnerable populations, as the virus evolves.

Validated models based on immunogenicity data will help make decisions on additional doses with existing or variant-modified vaccines.