A review of 65 years of human adenovirus seroprevalence

<b>Introduction</b>: Human adenovirus (HAdV)-derived vectors have been used in numerous pre-clinical and clinical trials during the last 40 years. Current research in HAdV-based vaccines focuses on improving transgene immunogenicity and safety. Because pre-existing humoral immunity against HAdV types correlate with reduced vaccine efficacy and safety, many groups are exploring the development of HAdV types vectors with lower seroprevalence. However, global seroepidemiological data are incomplete. <b>Areas covered</b>: The goal of this review is to centralize 65 years of research on (primarily) HAdV epidemiology. After briefly addressing adenovirus biology, we chronical HAdV seroprevalence studies and highlight major milestones. Finally, we analyze data from about 50 studies with respect to HAdVs types that are currently used in the clinic, or are in the developmental pipeline. <b>Expert opinion</b>: Vaccination is among the most efficient tools to prevent infectious disease. HAdV-based vaccines have undeniable potential, but optimization is needed and antivector immunity remains a challenge if the same vectors are to be administrated to different populations. Here, we identify gaps in our knowledge and the need for updated worldwide epidemiological data.

**引言**：人腺病毒（Human adenovirus, HAdV）载体在过去40年间已被广泛应用于多项临床前及临床试验。当前基于HAdV的疫苗研究重点在于提升转基因（transgene）的免疫原性与安全性。由于针对特定HAdV型别的预存体液免疫会导致疫苗效力与安全性下降，诸多研究团队正致力于开发血清阳性率更低的HAdV型别载体。但目前全球血清流行病学数据仍不完整。
**综述范围**：本综述旨在整合65年来（主要针对）HAdV流行病学的相关研究。在简要介绍腺病毒生物学特性后，我们将按时间脉络梳理HAdV血清阳性率相关研究，并着重标注关键里程碑。最后，我们将针对当前临床应用或处于研发管线中的HAdV型别，分析约50项研究的数据。
**专家观点**：疫苗接种是预防传染病最有效的手段之一。基于HAdV的疫苗具备不容置疑的应用潜力，但仍需优化；若将同一载体疫苗接种至不同人群，抗载体免疫仍是一项亟待解决的挑战。本文中，我们指出了当前认知存在的空白，以及更新全球流行病学数据的必要性。