Potential global impacts of alternative dosing regimen and rollout options for the ChAdOx1 nCoV-19 vaccine

Abstract

The high efficacy, low cost, and long shelf-life of the ChAdOx1 nCoV-19 vaccine positions it well for use in in diverse socioeconomic settings. Using data from clinical trials, an individual-based model was constructed to predict its 6-month population-level impact. Probabilistic sensitivity analyses evaluated the importance of epidemiological, demographic and logistical factors on vaccine effectiveness. Rollout at various levels of availability and delivery speed, conditional on vaccine efficacy profiles (efficacy of each dose and interval between doses) were explored in representative countries. We highlight how expedient vaccine delivery to high-risk groups is critical in mitigating COVID-19 disease and mortality. In scenarios where the availability of vaccine is insufficient for high-risk groups to receive two doses, administration of a single dose of is optimal, even when vaccine efficacy after one dose is just 75% of the two doses. These findings can help inform allocation strategies particularly in areas constrained by availability.

Fig. 1. Overall sensitivity analysis of vaccine effectiveness (%), based on UK data.

The boxplots show the median and interquartile ranges of the predicted vaccine effectiveness (as a percentage) on each of the outcomes for specific parameters. They were generated by aggregating all model simulations for each of the parameters, with each boxplot summarizing the variance in predicted vaccine efficacy for all possible combinations of the other parameters. The middle line shows the median, the lower and upper hinges correspond to the first and third quartiles, and the whiskers extend to the 5th and 95th percentiles. The full list of explored parameters and their descriptions can be found in Table 1. ATT population attack size (as a % of the population), TRG vaccine allocation (% of the population during study period), DSP second dose administered (% of the vaccinated population administered a second dose), BTI interval between first dose and booster dose, PD2 vaccine efficacy after the second dose; D2B vaccine efficacy of the first dose compared with the second dose (%); VCW immunity wane rate (days following last dose), DEL vaccine delivery speed.

Fig. 2. Optimal dose allocation.

The colored surfaces and respective contour lines indicate the ratio between the predicted vaccine effectiveness for a double-dose regimen vs a single-dose regimen, as indicated by the color-bar on the right. This ratio is a mean ratio, obtained by averaging out the ratios obtained in all model runs assuming the corresponding x and y parameter values and thus are not expected to be regular. Contour line 1 (thicker black line) indicates the parameter combinations for which there is no expected difference between giving everyone a single dose vs giving everyone two doses. For values greater than 1 (hot colors), a two-dose regimen is preferable, and for values less than 1 (cold colors), a single-dose regimen is preferable.

Fig. 3. Dose allocation thresholds in different countries.

The figure illustrates the parameter combinations that define the allocation threshold above which a two-dose regimen would be preferred over a single-dose regimen—these are the thick black contour lines in Fig. 2. The areas enclosed by the curves are 16.5%, 8%, and 3.8% for the UK, Brazil, and Uganda, respectively, which correlates almost perfectly with the proportion of the population above the age of 65 years in those countries. To calculate these areas, we vectorize each contour line to obtain the y-values at which the contour line is crossed for evenly spaced x-values (taking the highest y-value for duplicates). The resulting vector is then run through a composite trapezoid rule algorithm that computes the approximate area under the curve (auc function in the MESS R package).