Design and characterization of a self-assembling protein nanoparticle displaying HIV-1 Env V1V2 loop in a native-like trimeric conformation as vaccine antigen

• Published in: Nanomedicine 2019-02, Vol.16, p.206-216
• Main Authors: Karch, Christopher P., Bai, Hongjun, Torres, Oscar B., Tucker, Courtney A., Michael, Nelson L., Matyas, Gary R., Rolland, Morgane, Burkhard, Peter, Beck, Zoltan
• Format: Article
• Language: English
• Subjects: ALF; Conformational antibody; HIV-1; Nanovaccine; SAPN; V1V2; Vaccine
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2018.12.001

The RV144 HIV-1 clinical trial demonstrated modest vaccine efficacy and identified IgG antibodies against the Env V1V2 loop that inversely correlated with risk of infection. Based upon these results, we chose the Self-Assembling Protein Nanoparticle platform to present the V1V2 loop in a native-like conformation. We hypothesized this approach would lead to generation of conformation-specific IgG antibodies to V1V2. Our vaccine, V1V2-SHB-SAPN, was designed to present twenty copies of the V1V2 trimer. Particles were characterized for size, shape, and binding to monoclonal antibodies that recognize the V2 and V1V2 loops. Immunization induced IgG antibodies to V1, V2, V1V2 and to gp70V1V2 (AE/A244) capture antigens in mice. The presence of the Army Liposome Formulation induced a four-fold increase in IgG titers to gp70V1V2 and the adjuvanted V1V2-SHB-SAPN group had statistically higher IgG titers than sequence- and dose-matched V1V2 peptide controls. In conclusion, V1V2-SHB-SAPN vaccine presented the V1V2 loop in native-like conformation, as indicated by PGT145 binding, and induced high titers of IgG antibodies. Self-Assembling Protein Nanoparticle monomers with the V1V2 loop of HIV-1 Env protein self-assemble into a three dimensional nanoparticle (V1V2-SHB-SAPN) that displays 60 copies of the V1V2 loop forming 20 trimers in a native-like conformation (blue box). Mice were vaccinated with the V1V2-SHB-SAPN (blue box), V1V2-SHB-SAPN adjuvanted with Army Liposome Formulation (ALF) (black box), or V1 + V2 peptides adjuvanted with ALF (red box). V1V2-SHB-SAPN vaccines induced significantly higher IgG titers than mice vaccinated with V1 and V2 peptides. [Display omitted]