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dc.contributor.authorWhitaker, Neal
dc.contributor.authorHickey, John M.
dc.contributor.authorKaur, Kawaljit
dc.contributor.authorXiong, Jian
dc.contributor.authorSawant, Nishant
dc.contributor.authorCupo, Albert
dc.contributor.authorLee, Wen-Hsin
dc.contributor.authorOzorowski, Gabriel
dc.contributor.authorMedina-Ramírez, Max
dc.contributor.authorWard, Andrew B.
dc.contributor.authorSanders, Rogier W.
dc.contributor.authorMoore, John P.
dc.contributor.authorJoshi, Sangeeta B.
dc.contributor.authorVolkin, David B.
dc.contributor.authorDey, Antu K.
dc.date.accessioned2020-11-18T15:12:47Z
dc.date.available2020-11-18T15:12:47Z
dc.date.issued2019-02-15
dc.identifier.citationWhitaker, N., Hickey, J. M., Kaur, K., Xiong, J., Sawant, N., Cupo, A., Lee, W. H., Ozorowski, G., Medina-Ramírez, M., Ward, A. B., Sanders, R. W., Moore, J. P., Joshi, S. B., Volkin, D. B., & Dey, A. K. (2019). Developability Assessment of Physicochemical Properties and Stability Profiles of HIV-1 BG505 SOSIP.664 and BG505 SOSIP.v4.1-GT1.1 gp140 Envelope Glycoprotein Trimers as Candidate Vaccine Antigens. Journal of pharmaceutical sciences, 108(7), 2264–2277. https://doi.org/10.1016/j.xphs.2019.01.033en_US
dc.identifier.urihttp://hdl.handle.net/1808/30872
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractThe induction of broadly neutralizing antibodies (bNAbs) is a major goal in the development of an effective vaccine against HIV-1. A soluble, trimeric, germline (gI) bNAb-targeting variant of the HIV-1 envelope glycoprotein (termed BG505 SOSIP.v4.1-GT1.1 gp140, abbreviated to GT1.1) has recently been developed. Here, we have compared this new immunogen with the parental trimer from which it was derived, BG505 SOSIP.664 gp140. We used a comprehensive suite of biochemical and biophysical methods to determine physicochemical similarities and differences between the 2 trimers, and thereby assessed whether additional formulation development efforts were needed for the GT1.1 vaccine candidate. The overall higher order structure and oligomeric states of the 2 vaccine antigens were quite similar, as were their thermal, chemical, and colloidal stability profiles, as evaluated during accelerated stability studies. Overall, we conclude that the primary sequence changes made to create the gl bNAb-targeting GT1.1 trimer did not detrimentally affect its physicochemical properties or stability profiles from a pharmaceutical perspective. This developability assessment of the BG505 GT1.1 vaccine antigen supports using the formulation and storage conditions previously identified for the parental SOSIP.664 trimer and enables the development of GT1.1 for phase I clinical studies.en_US
dc.description.sponsorshipBill and Melinda Gates Foundation Collaboration for AIDS Vaccine Development (OPP1147661)en_US
dc.description.sponsorshipBill and Melinda Gates Foundation Collaboration for AIDS Vaccine Development (OPP1153692)en_US
dc.description.sponsorshipNIH HIVRAD grant P01 AI 110657en_US
dc.description.sponsorshipAids Fonds grant 2016019en_US
dc.publisherElsevieren_US
dc.rights© 2019 The Authors. Published by Elsevier Inc. on behalf of the American Pharmacists Association®.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBG505en_US
dc.subjectgp140en_US
dc.subjectTrimersen_US
dc.subjectHIV-1 Enven_US
dc.subjectDevelopability assessmenten_US
dc.subjectStabilityen_US
dc.subjectFormulationen_US
dc.subjectVaccineen_US
dc.titleDevelopability Assessment of Physicochemical Properties and Stability Profiles of HIV-1 BG505 SOSIP.664 and BG505 SOSIP.v4.1-GT1.1 gp140 Envelope Glycoprotein Trimers as Candidate Vaccine Antigensen_US
dc.typeArticleen_US
kusw.kuauthorWhitaker, Neal
kusw.kuauthorHickey, John M.
kusw.kuauthorKaur, Kawaljit
kusw.kuauthorXiong, Jian
kusw.kuauthorSawant, Nishant
kusw.kuauthorJoshi, Sangeeta B.
kusw.kuauthorVolkin, David B.
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.1016/j.xphs.2019.01.033en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC6595180en_US
dc.rights.accessrightsopenAccessen_US


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© 2019 The Authors. Published by Elsevier Inc. on behalf of the American Pharmacists Association®.
Except where otherwise noted, this item's license is described as: © 2019 The Authors. Published by Elsevier Inc. on behalf of the American Pharmacists Association®.