A Murine Monoclonal Antibody With Potent Neutralization Ability Against Human Adenovirus 7

Rong Wang,Ying Huang,Yunzhou Yu,Lei Chen,Quan Zhou,Zhixin Yang,Jiansheng Lu

doi:10.3389/fcimb.2019.00417

Abstract

B1-type human adenoviruses (HAdVs) HAdV-3, HAdV-7, and HAdV-55 have caused epidemics in North America, Asia, and Europe. However, to date, no adenovirus vaccines or antiviral drugs have been approved for general use. In the present work, a scFv-phage immune library was constructed and mouse monoclonal antibody (MMAb) 10G12 was obtained through selection. 10G12 is specific for HAdV-7 and binds the hexon loop1 and loop2 (LP12), resulting in strong neutralization activity against HAdV-7. Additionally, it is stable in serum and buffer at various pH values. The findings provide insight into adenovirus and antibody responses and may facilitate the design and development of adenovirus vaccines and antiviral drugs.

Highlights

Human adenoviruses (HAdVs), non-enveloped, icosahedral, double-stranded DNA viruses spanning > 85 genotypes, are classified into seven species (A–G) (Yoshitomi et al, 2017)
Female BALB/c mice at 6–8 weeks old were immunized with inactivated human adenoviruses (HAdVs)-7, and spleens were harvested for RNA extraction after four booster injections
variable heavy (VH) and variable light (VL) of 10G12, 10A4, 1B1, and 5D12 were recloned into pMABG1 or pMABKa to generate murine IgG1 molecules

Summary

Introduction

Human adenoviruses (HAdVs), non-enveloped, icosahedral, double-stranded DNA viruses spanning > 85 genotypes, are classified into seven species (A–G) (Yoshitomi et al, 2017). HAdV infection is characterized by a broad spectrum of disease symptoms in humans, including sore throat, pneumonia, fever, and acute otitis media, with most cases involving gastrointestinal symptoms that vary with infection genotype (Arnold et al, 2010; Kunz and Ottolini, 2010). Symptoms are generally mild and self-limiting in immune-competent adults, but outbreaks of acute respiratory diseases (ARDs), such as community-acquired pneumonia (CAP), can occur in newborns, school students, and military recruits (Tan et al, 2016). No vaccines for the general population available for HAdVs, and only vaccines against HAdV types 4 and 7 have been developed for the USA military (Russell et al, 2006; Kajon et al, 2015). No antiviral drugs or efficient antiviral therapies have been approved for treating HAdVs (Echavarría, 2008)

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