Division of General Internal Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
State University of New York Upstate Medical University, Syracuse, NY, USA.
Lancet Infect Dis. 2018 Oct;18(10):e333-e338. doi: 10.1016/S1473-3099(18)30126-9. Epub 2018 May 18.
Dengue virus infections cause a substantial public health burden in tropical and subtropical regions. A single dengue vaccine has been approved by regulatory authorities in 19 countries, but concerns regarding vaccine safety in people who are dengue naive at the time of immunisation has introduced uncertainty into the vaccine's future. As other dengue vaccines complete or enter large-scale efficacy trials, we argue that foundational work by Sabin, historic epidemiological observations of dengue outbreaks, and prospective cohort studies in Asia and the Americas indicate that modifications must be made to the methods of assessing dengue vaccines. In this Personal View, we review and relate previous data that supports a dynamic role of cross-protective dengue immunity to the goals and challenges of measuring and interpreting dengue vaccine immunogenicity, efficacy, and safety in clinical trials. We suggest that for partly protective vaccines, temporary cross-protective immunity could lead to overestimation of vaccine safety and efficacy in the early years following vaccination. We recommend that assessment of dengue vaccines should span several years, involve active surveillance to clinically characterise incident infections and regular blood draws to define kinetic changes in immunological profiles, and include sample sizes that are large enough to support detailed analyses of vaccine trial subgroups, such as individuals who are dengue naive.
登革热病毒感染在热带和亚热带地区造成了巨大的公共卫生负担。一种登革热疫苗已获得 19 个国家的监管机构批准，但由于人们对疫苗在免疫接种时对登革热初染者的安全性存在担忧，这给疫苗的未来带来了不确定性。随着其他登革热疫苗的完成或进入大规模疗效试验，我们认为，Sabin 的基础工作、登革热暴发的历史流行病学观察以及亚洲和美洲的前瞻性队列研究表明，必须修改评估登革热疫苗的方法。在这篇观点文章中，我们回顾和关联了以前的数据，这些数据支持了交叉保护的登革热免疫的动态作用，以实现衡量和解释临床试验中登革热疫苗免疫原性、疗效和安全性的目标和挑战。我们建议，对于部分保护性疫苗，在接种疫苗后的早期，暂时的交叉保护免疫可能会导致对疫苗安全性和疗效的高估。我们建议，登革热疫苗的评估应持续数年，包括主动监测以临床描述偶发感染，并定期采血以确定免疫谱的动态变化，并包括足够大的样本量，以支持对疫苗试验亚组（如登革热初染者）进行详细分析。
