The World Health Organization (WHO) has recently issued an interim statement on booster doses for COVID-19 vaccination.
Booster doses are administered to a vaccinated population that has completed a primary vaccination series (currently one or two doses of Emergency Use License COVID-19 vaccine depending on the product) when, with time, the immunity and clinical protection has fallen below a rate deemed sufficient in that population. The objective of a booster dose is to restore vaccine effectiveness from that deemed no longer sufficient.
Additional doses of a vaccine may be needed as part of an extended primary series for target populations where the immune response rate following the standard primary series is deemed insufficient. The objective of an additional dose in the primary series is to enhance the immune response to establish a sufficient level of effectiveness against disease. In particular, immunocompromised individuals often fail to mount a protective immune response after a standard primary series, but also older adults may respond poorly to a standard primary series with some vaccines.
The Director-General of WHO has called for a moratorium on booster vaccination for healthy adults until the end of 2021 to counter the persisting and profound inequity in global vaccine access. While many countries are far from reaching the 40% coverage target by the end of 2021, other countries have vaccinated well beyond this threshold, already reaching children and implementing extensive booster vaccination programmes.
While vaccine supply is growing, it is not evenly distributed. Lower income countries have had far less access, and face unpredictable and irregular supply. Within countries, equity considerations support improving coverage of the primary vaccination series in high risk populations as the top priority use of vaccine doses.
The primary global goal for the acute phase of the pandemic is to reduce deaths and severe disease due to COVID-19 and to protect the health system. The level of population vaccination coverage needed to achieve this goal may differ between countries.
The vast majority of current infections and COVID-19 cases are observed in unvaccinated people. If breakthroughs occur in vaccinated persons, in most cases events are less severe than those in unvaccinated persons. However, emerging data consistently show a decline in vaccine effectiveness against SARS-CoV2 infection and COVID-19 with time since vaccination, and more significant decline in older adults.
The degree of waning of immunity differs between vaccine products and target populations. Circulating viruses – in particular variants of concern; the extent of prior infection within a community at the time of primary vaccination; the primary vaccination schedule used (i.e. dose interval) and intensity of exposure are all likely to play a role in the findings on waning of protection but cannot be systematically assessed from current studies.
All studies on booster doses to date show a strong anamnestic (renewed, rapid production of antibody on subsequent encounter with an antigen) immunological response achieving or improving upon the peak antibody levels following the primary immunization series, but with insufficient data and too little follow-up to assess the kinetics and duration of the response. Both homologous (booster dose is of the same vaccine used in primary vaccination) and heterologous (booster dose is of a different vaccine than what was used in primary vaccination) booster regimens are immunologically effective.
No low-income country has yet introduced a booster vaccination programme. The most commonly prioritized target populations for booster doses are older adults, health workers and immunocompromised individuals (in immunocompromised individuals the booster dose is considered as an additional primary series vaccination dose by WHO). The degree of primary vaccination coverage in the eligible adult population varies. In several of the 120 countries which are administering booster doses the coverage rates for complete primary vaccination are below 30%.
In view of the continued supply uncertainties in global vaccine access and equity, individual country vaccine booster dose policy decisions need to balance the public health benefits to their population with support for global equity in vaccine access necessary to address the virus evolution and pandemic impact.
Of concern are broad-based booster programmes, including the booster vaccination of population sub-groups at lower risk of severe disease.
The first priority of a vaccination programme is to reduce mortality and severe disease and to protect health systems. The most important measure to achieve this goal is to maximize coverage among those most likely to become seriously ill and those most likely to become infected especially those who are critical for health system functioning. In order to do this, primary series coverage and selective booster options must be weighed and prioritized carefully. This priority also contributes to socioeconomic recovery, as the severity of COVID-19 and its potential to overwhelm health systems constitute a primary rationale for public health and social measures that restrict social and economic activity. To use vaccines first for those at lower risk of severe disease before achieving high primary series coverage and sustained protection through selective booster doses for those most likely to become seriously ill will reduce the impact that could be secured with the ongoing limited vaccine supply.
Mathematical modeling shows that greater reductions in mortality may be achieved by administering booster doses to high-risk populations than using those same doses for primary immunization of lower risk populations.
WHO is currently not recommending the general vaccination of children and adolescents as the burden of severe disease in these age groups is low and high coverage has not yet been achieved in all countries among those groups who are at highest risk of severe disease.
Additional data needed for booster vaccination policies include:
1. Assessing the need for booster doses:
Refined data on epidemiology and burden of disease:
- Epidemiology of breakthrough cases, by disease severity, age, co-morbidity and risk groups, exposure, type of vaccine and time since vaccination, and in the context of variants of concern
Refined vaccine-specific data:
- Efficacy, effectiveness, duration of protection of vaccination in the context of circulating variants of concern.
- Supplementary evidence from immunological studies assessing binding and neutralizing antibodies over time, as well as biomarkers of cellular and durable humoral immunity.
2. Assessing the performance of booster doses:
- Data on duration of protection of homologous and heterologous boosters.
- Safety and reactogenicity of booster vaccination, including heterologous boosting from larger-scale studies.
- Impact of booster vaccination on transmission.
3. Additional considerations include:
- Optimal timing of booster doses, possibility for dose-sparing for booster doses (e.g. fractional doses), booster needs in previously infected individuals, programmatic feasibility and sustainability, community perception and demand as well as equity considerations.
- Refined modeling studies to guide strategies to optimize the impact of vaccination.
Introducing booster doses should be firmly evidence-driven and targeted to the population groups at highest risk of serious disease and those necessary to protect the health system. To date, the evidence indicates a minimal to modest reduction of vaccine protection against severe disease over the 6 months after the primary series.
Evidence on waning vaccine effectiveness, in particular a decline in protection against severe disease in high-risk populations, calls for the development of vaccination strategies optimized for prevention of severe disease, including the targeted use of booster vaccination.
More data will be needed to understand the potential impact of booster vaccination on the duration of protection against severe disease, but also against mild disease, infection, and transmission, particularly in the context of emerging variants. Over time, as vaccination programmes effectively protect populations from severe disease and death, the protection against milder disease and the reduction of transmission become important additional considerations.
Link to the WHO interim statement on booster doses for COVID-19 vaccination: