A review of 65 years of human adenovirus seroprevalence

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Adenovirus
• vaccination
• gene therapy
• immunology
• seroepidemiology

Acknowledgment

We particularly thanks Chloé Houques, Lumen Ishimwe and Aboudou Djobo for their technical help during seroepidemiological studies.

Article highlights

• A human adenovirus (HAdV) were isolated in 1953 by Rowe and colleagues from adenoid tissue.

• HAdVs are nonenveloped particles containing a double-stranded linear DNA genome and belong to the family Adenoviridae and the genus Mastadenovirus, grouped into species A–G and classified in ‘types’ based on serology and sequence.

• HAdVs cause mild, self-limiting infections in immunocompetent people with an array of clinical manifestations, targeting the lower respiratory, digestive and ocular tracts (depending of the type), predominantly children, and people in close contact situation.

• -HAdV-derived vectors have been explored during the last 40 years and, despite challenges along the way, have become powerful tools for in vivo gene transfer.

• HAdV have been used in numerous vaccine trials, including a multitude of tumor-associated antigens and infectious agents.

• The use HAdV vectors is not risk free because pre-existing immunity creates challenges for their widespread utility as vaccines.

• HAdV-C5 is the best characterized vector system, which is also the most common type that infects humans worldwide.

• Clinical use of HAdV-C5 vectors exposed some limitations, drawbacks, and side effect are associated with pre-existing humoral and cellular immunity.

• In 1999, a death in a gene therapy trial remind us the critical need for fundamental research concerning HAdV use.

• In 2008, the HVTN502 vaccine STEP trails was prematurely interrupted due to lack of efficacy and increased risk of HIV acquisition in HAdV-C5 seropositive patients.

• To circumvent pre-existing immunity, vectors derived from ‘rare’ human or from animal AdVs were progressively developed. However, selective seroprevalence data have been incomplete and misleading.

• By 2018, hundreds of vaccines (and cancer) trials have used, or are using, HAdV-based vectors.

• Many studies and clinical trials are based on results that were generated more than 40 years ago.

• Seroepidemiological data were mostly performed for North America, Western Europe, China and Japan. HAdV seroepidemiology data from South America, Australasia and for most countries from Africa are limited and incomplete

• HAdV-D26 seroprevalence appears relatively high in Africa and Asia and low in North America and Europe and HAdV-B35 seroprevalence is reasonably low worldwide, according to the few studies performed.

• NAbs against some NHP AdVs can be detected in humans. Cross-reactivity is likely the reason.

• Technical procedures performed for seroepidemiologocal investigations contain noteworthy variation between studies, which make sometimes comparisons difficult.

• We encourage worldwide seroepidemiological studies, development of fundamental research on basic vector biology and interactions between HAdV and preexisting host immunity, systematic HIV surveillance in the trial endpoints, standardization of technical procedure for seroepidemiology investigations and improvement of a North-South collaborations.

• Determining HAdV seroprevalence will be challenging mostly due to increasing international travel and immigrations, and because of difficult social, medical, political, and military situations in specific areas.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for the article can be accessed here.

Additional information

Funding

This paper was supported by funding from the Centre Muraz (Burkina Faso); The Ebovac 2 project (Grant 115861 - EBOVAC2), Campus France, La fondation Pierre Fabre and the University of Montpellier.