TY - JOUR
T1 - Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence
AU - Sliepen, Kwinten
AU - Han, Byung Woo
AU - Bontjer, Ilja
AU - Mooij, Petra
AU - Garces, Fernando
AU - Behrens, Anna-Janina
AU - Rantalainen, Kimmo
AU - Kumar, Sonu
AU - Sarkar, Anita
AU - Brouwer, Philip J. M.
AU - Hua, Yuanzi
AU - Tolazzi, Monica
AU - Schermer, Edith
AU - Torres, Jonathan L.
AU - Ozorowski, Gabriel
AU - van der Woude, Patricia
AU - de la Peña, Alba Torrents
AU - van Breemen, Mariëlle J.
AU - Camacho-Sánchez, Juan Miguel
AU - Burger, Judith A.
AU - Medina-Ramírez, Max
AU - González, Nuria
AU - Alcami, Jose
AU - LaBranche, Celia
AU - Scarlatti, Gabriella
AU - van Gils, Marit J.
AU - Crispin, Max
AU - Montefiori, David C.
AU - Ward, Andrew B.
AU - Koopman, Gerrit
AU - Moore, John P.
AU - Shattock, Robin J.
AU - Bogers, Willy M.
AU - Wilson, Ian A.
AU - Sanders, Rogier W.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066988569&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31142746
U2 - https://doi.org/10.1038/s41467-019-10262-5
DO - https://doi.org/10.1038/s41467-019-10262-5
M3 - Article
C2 - 31142746
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2355
ER -