In a recent study published in Nature Communications, a group of researchers examined
the effectiveness of updated vaccines and variant-matched boosters against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant and their potential to reduce hospitalizations and deaths over one year.
Study: Estimating long-term vaccine effectiveness 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 have significantly reduced coronavirus disease 2019 (COVID-19) cases, hospitalizations, and deaths globally.
However, the emergence of variants of concern has diminished the vaccines' effectiveness in preventing infection and transmission, though they still offer protection against severe outcomes.
The Omicron variant and its subtypes have become dominant, causing repeated infections due to waning immunity. New bivalent vaccines targeting Omicron have shown higher immunogenicity.
As the virus evolves, estimating vaccine efficacy becomes challenging, and decisions on new vaccines and boosters will rely on immunogenicity and safety data rather than clinical trials.
About the study
The present study used empirical data on vaccine effectiveness against mild disease, hospitalizations, and deaths caused by the 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 primary analysis, the authors used data from all age groups from studies alongside data for the >65 age group. However, there was no stratification by sex or gender in the original studies, and data on prior infection were not available, potentially biasing the vaccine effectiveness estimates.
The immunological model used a biphasic exponential decay function to represent the individual's immunity levels (IL) after vaccination. A logistic relationship was considered between IL and vaccine effectiveness for mild disease, hospitalization, and death.
Further, 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 regime used for the initial doses. As an alternative exploration, they considered a vaccine- and dose-dependent boost to IL, restoring IL after the third and subsequent doses based on the magnitude of the boost and IL achieved post-dose 2.
This approach linked the IL achieved at subsequent doses to the vaccine regime used for the main course but not the time since dose 2.
The study used estimates of relative neutralization titers reported in other studies to project variant-adapted vaccine effectiveness. This was used to estimate the potential benefit of variant-adapted vaccines compared to ancestral vaccines.
Study results
The results of the present study revealed that the immunological model fits well with observed vaccine effectiveness data for three vaccines used in England and accurately reproduces the decline in effectiveness against both Omicron variants over a year.
The estimated reduction in immune level against the Omicron variant compared to Delta is 5.1-fold. Applying reductions estimated from immunogenicity data to the relationship inferred against the Wuhan virus predicts more pessimistic vaccine effectiveness against both variants than direct model fitting.
According to the authors' findings, mRNA-1273 exhibited the highest immune response when comparing three vaccines, followed by BNT162b2, and then AZD1222. The study also revealed that the initial period's immune level decay has a half-life of 35 days, while the subsequent decline has an estimated half-life of 581 days.
Short-term projections for vaccine effectiveness against the Omicron variant indicated that 180 days after the third dose, effectiveness against hospitalization declined to 49.7% for AZD1222, 70.3% for mRNA-1273, and 64.1% for BNT162b2.
One year after vaccination, the predicted protection levels further declined to 38.0% for AZD1222, 59.5% for mRNA-1273, and 52.6% for BNT162b2, offering relatively low protection against infection or mild disease and moderate protection against hospitalization.
The study also explored the potential benefit of variant-adapted vaccines. Variant-adapted vaccines are estimated to provide more sustained protection over time against both mild disease and hospitalization compared to administering the ancestral vaccine as a fourth dose.
Discussion
As the world faces the endemic circulation of SARS-CoV-2, understanding COVID-19 vaccine effectiveness against different variants becomes crucial.
This study presents a modeling framework that integrates knowledge about the utility of neutralizing antibody titres (NAT) as a measure of protection with population-based vaccine effectiveness data.
The model allows short-term projections of vaccine effectiveness beyond the observed period, aiding ongoing vaccination strategies and booster decisions for high-risk populations. However, challenges remain due to the complexity of immunity development against the virus and its variants.
The study shows that while the ancestral vaccines offer initial high protection, their effectiveness diminishes over time due to waning immunity and immune escape by the Omicron variant. Switching to variant-adapted vaccines as the fourth dose can prevent nearly double the severe disease cases over a year compared to using the ancestral vaccine for the fourth dose.
The study emphasizes the importance of regular booster vaccinations in managing COVID-19, especially for vulnerable populations.
As SARS-CoV-2 continues to evolve, validated models estimating modified vaccine effectiveness based on immunogenicity data will be essential to assess the benefit of additional doses with existing or variant-modified vaccines.
Conclusions
The study presents a model integrating NAT and population-based vaccine effectiveness data to project short-term vaccine efficacy. Ancestral vaccines offer initial high protection but wanes over time due to Omicron's immune escape.
As the fourth dose, variant-adapted 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 aid decisions on additional doses with existing or variant-modified vaccines.
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