INVESTIGADORES
GOLDBAUM Fernando Alberto
artículos
Título:
Tandem repeats of the extracellular domain of Matrix 2 influenza protein exposed in Brucella lumazine synthase decameric carrier molecule induce protection in mice
Autor/es:
ALVAREZ P, ZYLBERMAN V, GHERSI G, BOADO L, GOLDBAUM FA AND MATTION N.
Revista:
VACCINE
Editorial:
ELSEVIER SCI LTD
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 31 p. 806 - 812
ISSN:
0264-410X
Resumen:
The antigenic variation of influenza virus represents a major prevention
problem. However, the ectodomain of the protein Matrix 2 (M2e) is
nearly invariant in all human influenza A strains and has been
considered as a promising candidate for a broadly protective vaccine
because antibodies to M2e are protective in animal models. In this work
we evaluated the possible use of Brucella abortus lumazine synthase
protein (BLS), a highly immunogenic decameric protein, as a carrier of
the M2e peptide. Chimeric proteins generated by the fusion of one or
four in tandem copies of M2e to BLS were efficiently expressed in
Escherichia coli and assembled in decameric subunits similarly to the
wild type BLS enzyme, as demonstrated by the comparative circular
dichroism spectra and size exclusion chromatography and static light
scattering analysis. The M2e peptides were stably exposed at the ten
N-terminal ends of each BLS molecule. Immunization of mice with purified
chimeras carrying only one M2e (BLS-M2e) copy elicited a significant
humoral immune response with the addition of different adjuvants. The
fusion of four in tandem copies of the M2e peptide (BLS-4M2e) resulted
in similar levels of humoral immune response but in the absence of
adjuvant. Survival of mice challenged with live influenza virus was 100%
after vaccination with BLS-4M2e adjuvanted with Iscomatrix(®)
(P<0.001) and 80% when adjuvanted with alum (P<0.01), while the
chimera alone protected 60% of the animals (P<0.05). The approach
described in this study is intended as a contribution to the generation
of universal influenza immunogens, through a simple production and
purification process and using safe carriers that might eventually avoid
the use of strong adjuvants.