TY - JOUR
T1 - Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle
AU - Brouwer, Philip J. M.
AU - Antanasijevic, Aleksandar
AU - Berndsen, Zachary
AU - Yasmeen, Anila
AU - Fiala, Brooke
AU - Bijl, Tom P. L.
AU - Bontjer, Ilja
AU - Bale, Jacob B.
AU - Sheffler, William
AU - Allen, Joel D.
AU - Schorcht, Anna
AU - Burger, Judith A.
AU - Camacho, Miguel
AU - Ellis, Daniel
AU - Cottrell, Christopher A.
AU - Behrens, Anna-Janina
AU - Catalano, Marco
AU - del Moral-Sánchez, Iván
AU - Ketas, Thomas J.
AU - LaBranche, Celia
AU - van Gils, Marit J.
AU - Sliepen, Kwinten
AU - Stewart, Lance J.
AU - Crispin, Max
AU - Montefiori, David C.
AU - Baker, David
AU - Moore, John P.
AU - Klasse, Per Johan
AU - Ward, Andrew B.
AU - King, Neil P.
AU - Sanders, Rogier W.
PY - 2019
Y1 - 2019
N2 - The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.
AB - The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072370284&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31537780
U2 - https://doi.org/10.1038/s41467-019-12080-1
DO - https://doi.org/10.1038/s41467-019-12080-1
M3 - Article
C2 - 31537780
SN - 2041-1723
VL - 10
SP - 4272
JO - Nature communications
JF - Nature communications
IS - 1
ER -