title: Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery.
abstract: Recombinant adenoviruses are used as vaccines, gene therapy vectors, and oncolytic viruses. However, the efficacy of such therapies is limited by pre-existing neutralizing antibodies (NAbs), especially when the virus is administered systemically for a wider biodistribution or to reach multiple metastases. To protect adenovirus against NAbs we inserted an albumin-binding domain (ABD) in the main adenovirus capsid protein, the hexon. This domain binds serum albumin to shield the virus upon systemic administration. The ABD-modified adenoviruses bind human and mouse albumin and maintain the infectivity and replication capacity in presence of NAbs. In pre-immunized mice non-modified viruses are completely neutralized, whereas ABD-modified viruses preserve the ability to transduce target organs, induce oncolysis, or generate immune responses to expressed proteins. Our results indicate that albumin coating of the virus capsid represents an effective approach to evade pre-existing NAbs. This strategy has translational relevance in the use of adenovirus for gene therapy, cancer virotherapy, and vaccination.
authors.affiliation: Virotherapy and Gene therapy Group, ProCure Program, Instituto Catalan de Oncología-IDIBELL, L'Hospitalet de Llobregat 08908, Spain.
authors.forename: Luis Alfonso
authors.initials: LA
authors.lastname: Rojas
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid 28049, Spain.
authors.forename: Gabriela N
authors.initials: GN
authors.lastname: Condezo
authors.affiliation: Virotherapy and Gene therapy Group, ProCure Program, Instituto Catalan de Oncología-IDIBELL, L'Hospitalet de Llobregat 08908, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno
authors.affiliation: Virotherapy and Gene therapy Group, ProCure Program, Instituto Catalan de Oncología-IDIBELL, L'Hospitalet de Llobregat 08908, Spain.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Fajardo
authors.affiliation: Virotherapy and Gene therapy Group, ProCure Program, Instituto Catalan de Oncología-IDIBELL, L'Hospitalet de Llobregat 08908, Spain.
authors.forename: Marcel
authors.initials: M
authors.lastname: Arias-Badia
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid 28049, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: San Martín
authors.affiliation: Virotherapy and Gene therapy Group, ProCure Program, Instituto Catalan de Oncología-IDIBELL, L'Hospitalet de Llobregat 08908, Spain. Electronic address: ralemany@iconcologia.net.
authors.forename: Ramon
authors.initials: R
authors.lastname: Alemany
mesh_terms: D000256:Adenoviridae / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism*; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D050504:Oncolytic Viruses / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012709:Serum Albumin
keywords: Adenovirus; Albumin; Albumin-binding domain; Neutralizing antibodies