Smm World Booster

[Klaudia Aricas]

TheWorld 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\r\n timing of a booster dose for the currently available COVID-19 vaccines which have received Emergency Use Listing (EUL). This statement reflects the current understanding of vaccine performance and supply as presented to SAGE on 7 December\r\n 2021. It summarizes and contextualizes current evidence on booster vaccination. In recent weeks the SARS-CoV2 Omicron variant has emerged. Data are currently insufficient to assess the impact of this new variant of concern on vaccine effectiveness,\r\n in particular against severe disease. The statements and conclusions in this document will therefore be updated as data become available.

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 (2). While many countries are far from reaching\r\n 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. At the time of release of this statement, globally\r\n about 20% of COVID-19 vaccine doses, daily, are used for booster or additional dose vaccination.

Vaccine booster dose policy decisions should be based on evidence of individual and public health benefit and obligations to secure global equity in vaccine access as a means to minimize health impacts and transmission, and thereby reduce the risk of\r\n variants and prolongation of the pandemic. 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\r\n improving coverage of the primary vaccination series in high risk populations as the top priority use of vaccine doses (3).

The WHO roadmap on the prioritization of vaccine use in situations of limited supply (hereafter: the Roadmap), (3) as well as the Strategy to Achieve Global COVID-19 Vaccination by mid-2022 (4), define a hierarchy of\r\n public health goals in accordance with progressively increasing control of the COVID-19 pandemic. Among those, 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\r\n 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\r\n show a decline in vaccine effectiveness against SARS-CoV2 infection and COVID-19 with time since vaccination, and more significant decline in older adults. This evidence is mostly based on observational studies that may be subject to confounding factors\r\n (5).

For some inactivated vaccines (CoronaVac and COVID-19 vaccine BIBP), WHO has already issued the recommendation for the administration of an additional dose to those aged 60 years or older as part of the primary series to make initial immunity\r\n more robust (7, 8).

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\r\n 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.

In several jurisdictions, booster vaccination has been authorized by regulatory authorities and added to the product labels of BNT162b2, mRNA 1273 and Ad26.COV2.S. In addition, for ChAdOx1-S [recombinant] and CoronaVac, COVID-19 vaccine BIBP, BBV152\r\n and NVX-CoV2373 vaccines, clinical trial data of booster doses are available. All studies to date show a strong anamnestic immunological response achieving or improving upon the peak antibody levels following the primary immunization series, but with\r\n insufficient data and too little follow-up to assess the kinetics and duration of the response. Both homologous and heterologous booster regimens are immunologically effective(9).

Because no correlate of protection has yet been defined, it is not possible to predict with high confidence vaccine performance of these heterologous schedules based on the immune response. Vaccine effectiveness data for a booster dose are being published\r\n from an increasing number of countries, but remain limited in follow-up time. All studies demonstrate an improvement in protection against infection; milder disease; as well as severe disease and death (10-14) .

Safety and reactogenicity studies are based on small-scale clinical trials and post-licensure data with limited follow-up. Overall, they show a similar safety profile to that observed after the second dose in the primary series. Regulatory authorities\r\n and advisory bodies have thus assessed a favourable benefit risk ratio of booster vaccination at an individual level.

At least 126 countries worldwide have already issued recommendations on booster or additional vaccination and more than 120 have started programmatic implementation. The majority of these countries are classified as high-income, or upper middle-income.\r\n 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\r\n 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 these countries which are administering booster doses the coverage\r\n 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\r\n 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. Global supply is increasing significantly and is projected to be sufficient for vaccination of the entire adult\r\n population globally, and boosters of high risk populations (as defined in the roadmap, in particular older adults and immunocompromised persons), by the first quarter of 2022. However, projections show that only later in 2022 supply will be\r\n sufficient for extensive use of boosters in all adults, and beyond, should they be broadly needed.

These use case principles are also supported by mathematical modeling on the optimization of public health impact of a limited vaccine supply. This modeling shows that greater reductions in mortality may be achieved by administering booster doses\r\n to high-risk populations than using those same doses for primary immunization of lower risk populations. As supply increases and vaccination is expanded to lower priority age groups, trade-offs may need to be considered as to prioritizing booster\r\n vaccination to high-risk populations over expanding primary immunization coverage to younger populations. WHO is currently not recommending the general vaccination of children and adolescents as the burden of severe disease in these age groups is\r\n low and high coverage has not yet been achieved in all countries among those groups who are at highest risk of severe disease (16).

The decision to recommend and implement a booster dose is complex and requires, beyond clinical and epidemiological data, a consideration of national strategic and programmatic priorities, and importantly an assessment of the prioritization of globally\r\n limited vaccine supply. In this context, priority should be given to the prevention of severe disease and sustaining health systems. Evidence is accumulating to inform global recommendations, which may be refined as additional data become available.\r\n Additional data needs can be grouped into the following categories:

The focus of COVID-19 immunization efforts must remain on decreasing death and severe disease, and the protection of the health care system. Public health and social measures continue to be an essential component of the COVID-19 prevention strategy, especially\r\n in light of the Omicron variant. In the context of ongoing global vaccine supply constraints and inequities, broad-based administration of booster doses risks exacerbating vaccine access by driving up demand in countries with substantial\r\n vaccine coverage and diverting supply while priority populations in some countries, or in subnational settings, have not yet received a primary vaccination series.

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\r\n of vaccine protection against severe disease over the 6 months after the primary series. Waning of effectiveness against all clinical disease and infection is more pronounced. Duration of protection against the Omicron variant may be altered and is\r\n under active investigation. 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\r\n disease, including the targeted use of booster vaccination.

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