The World Health Organization, with the support of the Strategic Advisory Group of Experts (SAGE) on Immunization and its COVID-19 Vaccines Working Group, continues to review the emerging evidence on the need for and timing of additional booster doses for the currently available COVID-19 vaccines which have received Emergency Use Listing (EUL).
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The statements and conclusions in this document will be updated as new data become available.
Booster doses should be offered based on evidence that doing so would have substantial impact on reducing hospitalization, severe disease and death, and to protect health systems.
The order of implementing booster doses to different population groups should follow that which has been laid out for the primary vaccination series – i.e., booster doses should be prioritized for higher priority-use groups before lower priority-use groups, unless there is adequate justification not to do so.
Such justification may include programmatic constraints or acceptability obstacles to uptake in higher priority-use groups that would result in vaccine wastage.
In such cases, strategies should be prioritized to improve vaccine delivery, community engagement, and social mobilization efforts to reach higher priority-use groups.
Within a given priority-use group, primary series vaccination will have greater impact per dose than additional doses.
Across priority-use groups, the benefits of additional doses for higher priority-use groups versus primary series doses for lower priority-use groups depends on country conditions, including supply and roll-out timelines, past epidemic dynamics and infection-induced immunity, vaccine product, vaccine effectiveness, and waning of protection.
When high primary series coverage rates have been achieved among subgroups at higher risk of severe disease and death (e.g., older adults), additional doses for these subgroups may yield greater reductions in severe disease and death than use of equivalent vaccine supply for primary series vaccination of lower priority-use groups.
The optimal interval between completion of a primary series and administration of additional doses has yet to be determined, and depends on epidemiological setting, vaccine product, targeted age groups, background seroprevalence, and circulation and frequency of specific variant of concerns (VoC).
As a general principle, an interval of 4–6 months since completion of the primary series could be considered, especially in the context of Omicron.
Booster doses should be considered for all COVID-19 vaccines having received EUL as per WHO’s product specific interim recommendations.
Available data for WHO EUL COVID-19 vaccine products suggest that vaccine effectiveness and immunogenicity are lower in immunocompromised persons (ICPs), compared to persons without immunocompromising conditions.
An additional dose included in an extended primary series enhances immune responses in some ICPs. Given the significant risk of severe COVID-19 for ICPs, if infected, WHO has already issued a recommendation for an extended primary series (i.e. third dose) as well as a booster dose (i.e. fourth dose) for ICPs, for all COVID-19 vaccines. Homologous (same vaccine platform) and heterologous (different vaccine platform) vaccines can be used for such booster doses.
Additional booster doses beyond the first booster dose are currently being offered by some countries (i.e. fourth dose to older adults and a fifth dose for immunocompromised persons).
Data on the usefulness of these additional booster doses is sparse and especially limited on the duration of further protection.
Data on additional booster doses as of May 2022 only exists for the mRNA vaccines, and not for other vaccine platforms.
Hence, in the following we only focus on the evidence with regards to additional booster for mRNA vaccines, while encouraging more data to be accrued for all vaccine platforms.
For longer-term considerations, there are significant uncertainties related to the evolution of the virus and the characteristics of future variants.
Given widespread transmission of Omicron globally, continued viral evolution with the emergence of new variants or sub lineages as is already being seen.
Development of a pan-SARS-CoV-2 or pan-sarbecovirus vaccines are needed, but the timeframe for their development is uncertain.
Meanwhile, the composition of the currently available COVID-19 vaccines may need to be updated to offer better protection against new VOCs which may be antigenically distinct. Current vaccines based on the index virus appear to maintain high VE against severe disease also in the context of current variants of concerns, but VE estimates against infection and symptomatic diseases are lower against Omicron.
Any update to vaccine composition would aim to elicit greater breadth in the immune response against circulating and emerging variants, in addition to retaining protection against severe disease and death.
The performance of any updated vaccine(s) may vary depending on the nature and magnitude of previously acquired immunity, recognizing that this immunity will be dependent upon different VOCs, different types of vaccines and their timing of administration. ■