Evaluation of lumazine synthase from Bacillus anthracis as a presentation platform for polyvalent antigen display.

Wei, Yangjie; Wahome, Newton; VanSlyke, Greta; Whitaker, Neal; Kumar, Prashant; Barta, Michael L; Picking, Wendy L; Volkin, David B; Mantis, Nicholas J; Middaugh, C Russell

Wei, Yangjie; Wahome, Newton; VanSlyke, Greta; Whitaker, Neal; Kumar, Prashant; Barta, Michael L; Picking, Wendy L; Volkin, David B; Mantis, Nicholas J; Middaugh, C Russell.

Afiliación

Wei Y; Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
Wahome N; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
VanSlyke G; Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
Whitaker N; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
Kumar P; Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, 12208.
Barta ML; Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
Picking WL; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
Volkin DB; Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
Mantis NJ; Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, 12208.
Middaugh CR; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.

Protein Sci ; 26(10): 2059-2072, 2017 Oct.

Article en En | MEDLINE | ID: mdl-28736824

RESUMEN

Polyvalent antigen display is an effective strategy to enhance the immunogenicity of subunit vaccines by clustering them in an array-like manner on a scaffold system. This strategy results in a higher local density of antigens, increased high avidity interactions with B cells and other antigen presenting cells, and therefore a more effective presentation of vaccine antigens. In this study, we used lumazine synthase (LS), an icosahedral symmetry capsid derived from Bacillus anthracis, as a scaffold to present 60 copies of a linear B cell epitope (PB10) from the ricin toxin fused to the C terminus of LS via four different linkers. We then investigated the effects of linker length, linker rigidity and formaldehyde crosslinking on the protein assembly, conformational integrity, thermal stability, in vitro antibody binding, and immunogenicity in mice. Fusion of the PB10 peptide onto LS, with varying linker lengths, did not affect protein assembly, thermal stability or exposure of the epitope, but had a minor impact on protein conformation. Formaldehyde crosslinking considerably improved protein thermal stability with only minor impact on protein conformation. All LS_PB10 constructs, when administered to mice by injection without adjuvant, elicited measurable anti-ricin serum IgG titers, although the titers were not sufficient to confer protection against a 10× lethal dose ricin challenge. This work sheds light on the biophysical properties, immunogenicity and potential feasibility of LS from B. anthracis as a scaffold system for polyvalent antigen display.

Asunto(s)

Vacunas contra el Carbunco; Antígenos Bacterianos; Bacillus anthracis; Epítopos de Linfocito B; Complejos Multienzimáticos; Vacunas de Subunidad; Animales; Vacunas contra el Carbunco/química; Vacunas contra el Carbunco/genética; Vacunas contra el Carbunco/inmunología; Vacunas contra el Carbunco/metabolismo; Anticuerpos Antibacterianos/sangre; Anticuerpos Antibacterianos/inmunología; Antígenos Bacterianos/química; Antígenos Bacterianos/genética; Antígenos Bacterianos/inmunología; Antígenos Bacterianos/metabolismo; Bacillus anthracis/enzimología; Bacillus anthracis/inmunología; Epítopos de Linfocito B/química; Epítopos de Linfocito B/genética; Epítopos de Linfocito B/inmunología; Epítopos de Linfocito B/metabolismo; Femenino; Inmunoglobulina G/sangre; Inmunoglobulina G/inmunología; Ratones; Modelos Moleculares; Complejos Multienzimáticos/química; Complejos Multienzimáticos/genética; Complejos Multienzimáticos/inmunología; Complejos Multienzimáticos/metabolismo; Estabilidad Proteica; Ricina/química; Ricina/genética; Ricina/inmunología; Ricina/metabolismo; Vacunas de Subunidad/química; Vacunas de Subunidad/genética; Vacunas de Subunidad/inmunología; Vacunas de Subunidad/metabolismo

Palabras clave

immunogenicity; lumazine synthase; polyvalent antigen display; ricin; stability; vaccine

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus anthracis / Epítopos de Linfocito B / Vacunas contra el Carbunco / Vacunas de Subunidad / Complejos Multienzimáticos / Antígenos Bacterianos Idioma: En Revista: Protein Sci Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos

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