Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus...

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Detalles Bibliográficos
Autores: Sliepen, Kwinten, Han, Byung Woo, Bontjer, Ilja, Mooij, Petra, Garces, Fernando, Behrens, Anna-Janina, Rantalainen, Kimmo, Kumar, Sonu, Sarkar, Anita, Brouwer, Philip J M, Hua, Yuanzi, Tolazzi, Monica, Schermer, Edith, Torres, Jonathan L, Ozorowski, Gabriel, van der Woude, Patricia, Torrents de la Peña, Alba, van Breemen, Mariëlle J, Camacho-Sánchez, Juan Miguel, Burger, Judith A, Medina-Ramírez, Max, Gonzalez-Fernandez, Nuria, Alcamí, José, LaBranche, Celia, Scarlatti, Gabriella, van Gils, Marit J, Crispin, Max, Montefiori, David C, Ward, Andrew B, Koopman, Gerrit, Moore, John P, Shattock, Robin J, Bogers, Willy M, Wilson, Ian A, Sanders, Rogier W
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/9255
Acceso en línea:http://hdl.handle.net/20.500.12105/9255
Access Level:acceso abierto
Palabra clave:AIDS Vaccines
Animals
Antibodies, Neutralizing
Consensus Sequence
Epitopes
HIV Antibodies
HIV-1
Macaca
Protein Multimerization
Rabbits
env Gene Products, Human Immunodeficiency Virus
Descripción
Sumario:Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

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