Conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein nanoparticles as a potential HIV vaccine.
The self-assembling protein nanoparticle (SAPN) is an antigen-presenting system that has been shown to be suitable for use as a vaccine platform. The SAPN scaffold is based on the principles of icosahedral symmetry, beginning from a monomeric chain that self-assembles into an ordered oligomeric state. The monomeric chain contains two covalently linked α-helical coiled-coil domains, an N-terminal de novo-designed pentameric tryptophan zipper and a C-terminal de novo-designed trimeric leucine zipper, which assemble along the internal symmetry axes of an icosahedron. In this study, we incorporated the membrane proximal external region (MPER) of HIV-1 gp41 from HXB2 into the N-terminal pentamer, referred to as MPER-SAPN, attempting to reproduce the α-helical state of the 4E10 epitope while maintaining a structurally less-constrained 2F5 epitope. Sprague-Dawley rats were immunized with MPER-SAPNs, and their sera were analyzed for induced humoral anti-HIV-1 responses. We show that high membrane proximal external region-specific titers can be raised via the repetitive antigen display of MPER on the SAPN without the need for adjuvant. However, none of the sera displayed a detectable neutralizing activity against HIV-1. Thus, 4E10- and 2F5-like neutralizing antibodies could not be elicited by MPER conformationally restrained in the SAPN context.
Molecular and Cell Biology Department, University of Connecticut, Storrs, 06250, USA.
Newton
N
Wahome
Tanya
T
Pfeiffer
Ina
I
Ambiel
Yongkun
Y
Yang
Oliver T
OT
Keppler
Valerie
V
Bosch
Peter
P
Burkhard
D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007114:Immunization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D009500:Neutralization Tests; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015700:HIV Envelope Protein gp41