New recommendation on yellow fever booster vaccination in Germany

On August 11, 2022, the Permanent Vaccination Commission in Germany ('Sta & BULL;ndige Impfkommission'; STIKO) updated the recommen-dations for the yellow fever (YF) vaccination in Germany.1 Briefly, all travellers to YF endemic countries and exposed laboratory personal should receive one booster vaccination & GE;10 years after the first vacci-nation [1]. This is in contrast to WHO recommendations and the current international health regulation, which state that a single YF vaccination confers livelong protection [2]. At this stage, no matter to which side one leans, there are arguments for, and against, retaining a booster recommendation for all. We would like to bring forward arguments which rather support adherence to the current WHO recommendations. The new STIKO recommendation is mainly based on a recent sys-tematic review and meta-analysis which attempted to address the duration of protection after a single YF vaccine [3]. This work certainly meets formal criteria for such an analysis. However, it appears ques-tionable whether the full complexity of a YF booster vaccination is appropriately accounted for as, first, the meta-analysis excluded all retrospective studies in the assessment of the sero-protection rate (neutralising antibody titres & GE;1:10 as surrogate of protection). In that particular matter, it is difficult to rely prima vista exclusively on a paucity of prospective studies specifically designed for the purpose of assessing primary yellow fever protection rates after ten years and more onwards. Owed to the specific study question, and in view of guidelines implications, it appears at least worthwhile to carefully consider whether or not retrospective studies should indeed be, or not, dismissed up front when investigating the matter of YF booster vaccination, or rather being included, as there is no technical reason to dismiss them up front on methodological grounds. Second, there is now an increasing body of evidence that not only the humoral but also the T-cell driven immune response is essential for a protection against the YF virus (YFV). YF-specific CD8+ memory T-cells were still detected 18 years post vaccination [4], and these memory cells appear to proliferate after re-exposure to the vaccine antigens both in immunocompetent and immune-compromised patients maintaining their cytotoxic and polyfunctional potential [5]. It is therefore highly likely, that an exposure to YFV is able to elicit a protective immune response even if the single vaccination dates back > 10 years, at least in individuals who received their primary vaccination later than in their first year of life [6]. A booster vaccination did not increase the frequency of these memory T-cells. Therefore, looking only at the sero-protection rate is falling short of looking at all levels of protection. Third, notification numbers of YF cases in Germany are low (five cases between 1999 and today, https://survstat.rki.de/) of which four were definitely not vaccinated (vaccination status unknown for one of those five individuals) [7,8]. Thus, the current strategy of a single vaccination did not lead to an increase of cases neither in that particular

Automated summary

The Permanent Vaccination Commission in Germany has updated its recommendations for yellow fever vaccination, conflicting with WHO recommendations. The article presents arguments supporting adherence to the WHO recommendations, including the complexity of booster vaccinations and the importance of T-cell driven immune response.