title: Tetraspanins displayed in retrovirus-derived virus-like particles and their immunogenicity.
abstract: Virus-like particles (VLPs) are a particular subset of subunit vaccines which are currently explored as safer alternatives to live attenuated or inactivated vaccines. VLPs derived from retrovirus (retroVLPs) are commonly used as scaffolds for vaccine candidates due to their ability to incorporate heterologous envelope proteins. Pseudotyping retroVLPs is however not a selective process therefore, host cellular proteins such as tetraspanins are also included in the membrane. The contribution of these host-proteins to retrovirus immunogenicity remains unclear. In this work, human cells silenced and not silenced for tetraspanin CD81 were used to produce CD81(-) or CD81(+) retroVLPs. We first analyzed mice immune response against human CD81. Despite effective silencing of CD81 in retroVLP producing cells, both humoral and cellular immune responses showed persistent anti-CD81 immunogenicity, suggesting cross reactivity to related antigens. We thus compared the incorporation of related tetraspanins in retroVLPs and showed that decreased CD81 incorporation in CD81(-) retro-VLPs is compensated by an increased incorporation of CD9 and CD63 tetraspanins. These results highlight the dynamic nature of host-derived proteins incorporation in retroVLPs membrane, which should be considered when retrovirus-based biopharmaceuticals are produced in xenogeneic cells.
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: H R
authors.initials: HR
authors.lastname: Soares
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Castro
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: H A
authors.initials: HA
authors.lastname: Tomás
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: A F
authors.initials: AF
authors.lastname: Rodrigues
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Gomes-Alves
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS_959, I3, F-75013 Paris, France; INSERM, UMR_S 959, I3, F-75013 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Bellier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS_959, I3, F-75013 Paris, France; INSERM, UMR_S 959, I3, F-75013 Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Klatzmann
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Faculdade de Ciências e Tecnologia/Universidade Nova de Lisboa, P-2825 Monte da Caparica, Portugal.
authors.forename: M J T
authors.initials: MJT
authors.lastname: Carrondo
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: P M
authors.initials: PM
authors.lastname: Alves
authors.affiliation: iBET - Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica, António Xavier, Universidade Nova de Lisboa (ITQB-UNL), Av. da República, 2780-157 Oeiras, Portugal. Electronic address: avalente@itqb.unl.pt.
authors.forename: A S
authors.initials: AS
authors.lastname: Coroadinha
mesh_terms: D000818:Animals; D003429:Cross Reactions; D005260:Female; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012190:Retroviridae; D060225:Tetraspanin 28 / Q000235:genetics / Q000276:immunology*; D060245:Tetraspanin 29 / Q000235:genetics / Q000276:immunology; D060149:Tetraspanin 30 / Q000235:genetics / Q000276:immunology; D059470:Tetraspanins / Q000235:genetics / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; D059470:Tetraspanins; D058425:Vaccines, Virus-Like Particle
keywords: CD63; CD81; CD9; Immunogenicity; RetroVLPs; Retrovirus; Tetraspanins; Vaccines; Viral vectors; Virus-like particles