Publications by authors named "Nicole Cibelli"

Article Synopsis
  • Bi-functional N-Hydroxysuccinimide (NHS) linkers are crucial in connecting immunogens with carrier proteins to enhance immune responses, particularly in HIV-1 vaccine development.
  • The study investigated the degradation kinetics of these linkers using reversed-phase liquid chromatography (RPLC-UV) to ensure effective conjugation before the linkers become inactive.
  • Three types of cross-linkers were examined for their degradation pathways, with specific kinetics reported for the Sulfosuccinimidyl (4-iodoacetyl) aminobenzoate (Sulfo-SIAB) linker.
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Article Synopsis
  • Conjugate-vaccine immunogens consist of a carrier protein, an antigen, and a crosslinker that connects the two while maintaining immune responses; this study focuses on the effects of different crosslinkers between an HIV-1 antigen (FP8) and the carrier protein (rTTHC).
  • The research evaluated various physical properties and immunogenic responses of seven different FP8-rTTHC conjugates with varying linker lengths and types, finding that most conjugates were well recognized by specific HIV-fusion-peptide antibodies, except those with the shortest and longest linkers, which showed reduced recognition.
  • Immunization tests in mice showed that conjugates with shorter (SIA) and
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The spike (S) glycoprotein of the pandemic virus, SARS-CoV-2, is a critically important target of vaccine design and therapeutic development. A high-yield, scalable, cGMP-compliant downstream process for the stabilized, soluble, native-like S protein ectodomain is necessary to meet the extensive material requirements for ongoing research and development. As of June 2021, S proteins have exclusively been purified using difficult-to-scale, low-yield methodologies such as affinity and size-exclusion chromatography.

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The spike (S) glycoprotein of the pandemic virus, SARS-CoV-2, is a critically important target of vaccine design and therapeutic development. A high-yield, scalable, cGMP-compliant downstream process for the stabilized, soluble, native-like S protein ectodomain is necessary to meet the extensive material requirements for ongoing research and development. As of June 2021, S proteins have exclusively been purified using difficult-to-scale, low-yield methodologies such as affinity and size-exclusion chromatography.

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High throughput process development (HTPD) using liquid handling robotics and RoboColumns is an established methodology in downstream process development to screen chromatography resins and optimize process designs to meet target product profiles. However, HTPD is not yet widely available for use in viral clearance capability of the resin due to a variety of constraints. In the present study, a BSL-1-compatible, non-infectious MVM model, MVM-VLP, was tested for viral clearance assessment with various resin and membrane chromatography operations in a HTPD mode.

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Metastable glycosylated immunogens present challenges for GMP manufacturing. The HIV-1 envelope (Env) glycoprotein trimer is covered by N-linked glycan comprising half its mass and requires both trimer assembly and subunit cleavage to fold into a prefusion-closed conformation. This conformation, the vaccine-desired antigenic state, is both metastable to structural rearrangement and labile to subunit dissociation.

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