Considerations for optimising deployment of AstraZeneca & SII/Covishield vaccines in a time-limited constrained supply situation - One More Push

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Considerations for optimising deployment of AstraZeneca & SII/Covishield vaccines in a time-limited constrained supply situation

PUBLISHED 21 September 2021
About the vaccine,

Key messages

 

    • The generic group of ChAdOx1-S [recombinant] vaccines includes AstraZeneca/AZD1222 and SII/Covishield vaccines. For prolonged efficacy using ChAdOx1-S vaccines, WHO recommends two standard doses (0.5ml) administered with an interval of 8 to 12 weeks between doses.

 

    • Clinical trials have demonstrated that after vaccination with a single 0.5ml dose, an efficacy as high at 76.0% (95% CI 59.3–85.9) could be expected against laboratory-confirmed Covid-19, as measured from 22 days after vaccination through 12 weeks.

 

    • Evidence has demonstrated sustained vaccine efficacy after a single 0.5ml dose for a period of up to 12 weeks (3 months), yet antibody concentrations declined by 34% through 90 days. 2 Limited data is available on the duration of efficacy or rapidly waning immunity past 12 weeks, and a second dose has been shown to maintain high efficacy.

 

    • Unpublished mathematical modeling demonstrates that when supply is very limited during the initial introduction period, vaccinating more people in the highest priority population group with one dose as opposed to vaccinating half that number with two doses, would substantially increase
      the number of deaths prevented, if the 1-dose vaccine efficacy is at least 50% of the 2-dose efficacy.

 

    • In view of the evidence suggesting the potential for disease rates to be reduced following administration of the first dose and data from mathematical modelling, national immunisation programmes faced with limited supply of AstraZeneca/AZD1222 or SII/Covishield vaccine might
      elect a strategy of vaccinating a maximum number of persons within a higher number of priority groups with a first dose and preferentially planning for the second dose to be provided at 12 weeks (3 months) later, or as soon as possible thereafter.

 

    • Given the equivalence of AstraZeneca/AZD1222 and SII/Covishield to ChAdOx1-S, the two products are interchangeable.

 

Purpose: This document provides an overview of the scientific basis and key programmatic considerations to guide national decision-making for countries on optimising the deployment of AstraZeneca/AZD1222 and SII/Covishield vaccines under circumstances where vaccine supply is constrained, and future quantities and delivery dates cannot be reliably predicted. Further details on the available evidence and key studies are available at the SAGE website, while resources for implementation and training are available at the COVID-19 vaccine introduction toolkit webpage.

Context: Currently, the global market supply of AstraZeneca/AZD1222 and SII/Covishield vaccines, both provided under the COVAX Facility, does not fully meet global demand.5 While supply is expected to increase through the second half of 2021, the frequency of shipments to countries remains uncertain in the near to medium term and residual shelf life at the time of delivery may be as short as three months. Countries receiving fewer doses than required to fully vaccinate all highest priority groups will be challenged to strike the proper balance across key objectives:

    • Maximizing immunity against COVID-19 in the highest priority groups according to the recommended schedule;

 

    • Reaching as many people within as many priority groups as quickly as possible, with at least one dose; and

 

    • Fully administering all doses available prior to their lot expiration date.

 

 

Evidence base

WHO SAGE interim recommendations on the AstraZeneca COVID-19 vaccines refer to a generic group of ChAdOx1-S [recombinant] vaccines against COVID-19. The ChAdOx1-S [recombinant] vaccine uses a DNA adenovirus vector to elicit antibodies to the SARS-CoV-2 spike protein. WHO recommendations apply to the AZD1222 product developed jointly by Oxford University (United Kingdom) and AstraZeneca, as well as to ChAdOx1-S [recombinant] vaccines produced by other manufacturers, namely AstraZeneca/AZD1222 (produced by AstraZeneca-SKBio in the Republic of Korea) and SII/Covishield
(produced by the Serum Institute of India). Each of these products rely on the AstraZeneca core clinical data and demonstrated equivalence in their regulatory and WHO reviews. Conditional marketing authorization (CMA) by the European Medicines Agency (EMA) of the AstraZeneca/AZD1222 vaccine was
received on 29 January 2021. WHO granted Emergency Use Listing (EUL) for both products on 15 February 2021.6 Current estimates on product efficacy are drawn from the pooled analysis of data from four randomised, controlled clinical trials conducted in the United Kingdom (two studies), Brazil, and South Africa, involving

approximately 24,000 adults aged 18 year and older. As the examined interval lengths between dose 1 and dose 2 varied across the different studies, inter-dose efficacy described below has been estimated. 7 For the purpose of describing the scientific evidence supporting these products, the generic name of ChAdOx1-S will be used in the table below. It should be noted that given the equivalence of AstraZeneca/AZD1222 and SII/Covishield to ChAdOx1-S, the two products are interchangeable.

Mathematical modelling. Current unpublished mathematical modeling demonstrates that when supply is very limited during the initial introduction period, vaccinating more people in the highest priority population group with one dose as opposed to vaccinating half that number with two doses would substantially increase the number of deaths prevented, as long as the 1-dose vaccine efficacy is at least 50% of the 2-dose efficacy. As supply increases and the highest priority populations all receive one dose, a decision about using supply to vaccinate that group with a second dose or advance with first doses to the next risk group is needed. The decision depends on the relative risk of mortality between the priority
risk groups, the relative vaccine efficacy of 1-dose and 2-doses, the durability of the 1-dose efficacy over time, and the supply pace.

As supply increases and the rollout moves to ever lower risk groups, the model indicates that the highest risk groups should be prioritized to complete their vaccination with a second dose in lieu of continuing to offer first doses to a lower priority group. The specific point at which this blended strategy should occur depends on supply volumes, pace, population sizes, relative disease risks, and vaccine efficacy characteristics. Prioritising first dose administration at the outset of the programme to highest priority groups is expected to provide greater benefit when supply is very limited; this holds true even when supply is insufficient to administer the second dose in a timely manner, as long as waning of first dose immunity is not very rapid.

Programmatic considerations

Given the short timelines from vaccine development to EUL, the available stability data for the AstraZeneca/AZD1222 and SII/Covishield vaccine only permit authorization with a shelf life of six months, as is the case for other COVID-19 vaccines. This is a much shorter shelf life than vaccines normally handled in the EPI programme, so any vaccination strategy with AstraZeneca/AZD1222 or SII/Covishield requires careful planning and accelerated implementation by countries to ensure that the vaccines can be administered prior to the lot expiration date.Given the global production constraints and unpredictable nature of the frequency and quantity of future shipments, each country will need to properly evaluate what is operationally relevant in their national context. A range of programmatic factors are cited below for consideration; many of the factors are interlinked and cannot be viewed independently. It is recommended that the NITAG plays a central role in thedecision-making process, actively participating in the assessment of the risks and benefits of each
alternative under consideration.

Conclusion

In view of the evidence suggesting the potential for disease rates to be reduced following administration of the first dose, national immunisation programmes faced with limited supply of AstraZeneca/AZD1222or SII/Covishield vaccine might elect a strategy of vaccinating a maximum number of persons within a higher number of the priority groups with a first dose and preferentially planning for the second dose to be provided at 12 weeks (3 months) later, or as soon as possible thereafter. Data supporting an extension beyond three months has yet to become available. It should be noted that clinical trials did not assess the impact on antibody response if the interval between administration of dose 1 and dose 2 is extended beyond 12 weeks, nor what impact this would have in relation to protection against any circulating SARS-CoV-2 virus variants. As further research on vaccine effectiveness is undertaken and risk monitoring associated with SARS-CoV2 viral mutations allows for a better assessment of required responses, further information will be made available.

Sources

Considerations for optimizing deployment of AstraZeneca/AZD1222 and SII/Covishield vaccines in a time-limited constrained supply situation

https://www.afro.who.int/sites/default/files/Covid-19/Techinical%20documents/Deployment_AZvaccines_16March_FINAL%20(1).pdf