The assembly conformation of rotavirus VP6 determines its protective efficacy against rotavirus challenge in mice
Por:
Pastor A.R., Rodríguez-Limas W.A., Contreras M.A., Esquivel E., Esquivel-Guadarrama F., Ramírez O.T., Palomares L.A.
Publicada:
19 may 2014
Resumen:
Viral protein assemblies have shown to be superior immunogens used in
commercial vaccines. However, little is known about the effect of
protein assembly structure in immunogenicity and the protection
conferred by a vaccine. In this work, rotavirus VP6, a polymorphic
protein that assembles into nanotubes, icosahedra (dlRLP) or trimers was
used to compare the immune response elicited by three different
assemblies. VP6 is the most antigenic and abundant rotavirus structural
protein. It has been demonstrated that antibodies against VP6 interfere
with the replication cycle of rotavirus, making it a vaccine candidate.
Groups of mice were immunized with either nanotubes, dlRLP or trimers
and the humoral response (IgG and IgA titers) was measured. Immunized
mice were challenged with EDIM rotavirus and protection against
rotavirus infection, measured as viral shedding, was evaluated.
Immunization with nanotubes resulted in the highest IgG titers, followed
by immunization with dlRLP. While immunization with one dose of
nanotubes was sufficient to reduce viral shedding by 70%, two doses of
dlRLP or trimers were required to obtain a similar protection. The
results show that the type of assembly of VP6 results in different
humoral responses and protection efficacies against challenge with live
virus. This information is important for the design of recombinant
vaccines in general. (C) 2014 Elsevier Ltd. All rights reserved.
Filiaciones:
Pastor A.R.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Rodríguez-Limas W.A.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Contreras M.A.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Esquivel E.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Esquivel-Guadarrama F.:
Facultad de Medicina, Universidad Autónoma Del Estado de Morelos, Cuernavaca, Morelos, Mexico
Ramírez O.T.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
Palomares L.A.:
Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Morelos, Mexico
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