Broadly neutralizing monoclonal antibodies against human adenovirus types 55, 14p, 7, and 11 generated with recombinant type 11 fiber knob

Abstract

The re-emerging human adenovirus types HAdV7, HAdV14, and HAdV55 of species B have caused severe lower respiratory tract diseases and even deaths during recent outbreaks. However, no adenovirus vaccine or therapeutic has been approved for general use. These adenoviruses attach to host cells via the knob domain of the fiber, using human desmoglein 2 as the primary cellular receptor. In this study, a recombinant HAdV11 fiber knob trimer (HAdV11FK) expressed in E. coli was shown to induce broadly neutralizing antibodies against HAdV11, -7, -14p1, and -55 in mice. Using HAdV11FK as an antigen, three monoclonal antibodies, 6A7, 3F11, and 3D8, with high neutralizing activity were generated. More importantly, the results of in vitro neutralization assays demonstrated that 3F11 and 3D8 cross-neutralized HAdV11, -7, and -55, but not HAdV14p1. The amino acids 251KE252 within the F-G loop may be the crucial amino acids in the conformational epitope recognized by 3F11, which is common to HAdV11, -7, -14p, and -55, but is not present in HAdV14p1 and HAdV3. A two-amino-acid deletion in the HAdV14p1 structure breaks the short alpha helix (248SREKE252) that is present in the HAdV7, -11, -55, and -14p fiber knob structures. Our findings add to the knowledge of adenovirus fiber structure and antibody responses and are important for the design of adenovirus vaccines and antiviral drugs with broad activity.

Development of two antigen-binding fragments to a conserved linear epitope of human adenovirus and their application in immunofluorescence

“…When the generated Fabs are used to detect antigens in nasopharyngeal swab samples, they are specific to HAdV and will not recognize other viruses, ensuring that the results are reliable. Some mAbs with specificity to HAdV have been reported, but they recognize only one or several types within a single species[16, 28, 29]. In this study, the generated Fabs recognized several types within species B and HAdV-E4.…”

“…Fabs 2A6 and 4E2 were able to bind to several types of HAdV in species B and E, as assessed by CLEIA and IFA. We had recently reported that three broadly neutralizing mAbs were identified with specific reactivity to a conformational neutralization epitope in the knob proteins of several types of HAdV in species B[29]. Therefore, the knob proteins of HAdV-B3, E4, and C5 (negative control) were expressed to examine whether both Fabs also bind to the knob protein.…”

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

“…Despite more than 85 genotypes have been identified for HAdVs, few neutralizing antibodies have been reported. Tian et al (2018a) reported that the recombinant trimeric HAdV-11 fiber knob region is responsible for cross-neutralizing antibody responses against HAdV-11, -7, -14p1, and -55 in mice. Three neutralizing MAbs, 6A7, 3F11, and 3D8, were obtained via mouse hybridoma fusion, of which 3F11 and 3D8 cross-neutralized HAdV-11,-7, and -55, but not HAdV-14p1 (Tian et al, 2018a).…”

“…Tian et al (2018a) reported that the recombinant trimeric HAdV-11 fiber knob region is responsible for cross-neutralizing antibody responses against HAdV-11, -7, -14p1, and -55 in mice. Three neutralizing MAbs, 6A7, 3F11, and 3D8, were obtained via mouse hybridoma fusion, of which 3F11 and 3D8 cross-neutralized HAdV-11,-7, and -55, but not HAdV-14p1 (Tian et al, 2018a). Feng et al (2018) previously demonstrated that a fiber-specific antibody in sera contributed to cross-neutralizing activity against HAdV-14 and HAdV-55.…”

Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer

“…In many cancers of epithelial origin, such as breast cancer, cluster of differentiation 44 (CD44) is a main up-regulated HA receptor on the cancer cell surface (Huang and Huang, 2018b; Liao et al., 2018; Maudens et al., 2018). HA can regulate cancer cell proliferation and migration via CD44 (Safdar et al., 2017; Tian et al., 2018). Thus, HA has gained attention as a promising cancer targeting ligand for anti-cancer drug delivery.…”