Immune response to a potyvirus with exposed amino groups available for chemical conjugation

Abstract

BackgroundThe amino terminus of the tobacco etch virus (TEV) capsid protein is located on the external surface of infectious TEV particles, as proposed by previous studies and an in silico model. The epsilon amino groups on the exposed lysine residues are available for chemical conjugation to any given protein, and can thus act as antigen carriers. The availability of amino groups on the surfaces of TEV particles was determined and the immune response to TEV evaluated.ResultsUsing a biotin-tagged molecule that reacts specifically with amino groups, we found that the TEV capsid protein has amino groups on its surface available for coupling to other molecules via crosslinkers. Intraperitoneal TEV was administered to female BALB/c mice, and both their humoral and cellular responses measured. Different IgG isotypes, particularly IgG2a, directed against TEV were induced. In a cell proliferation assay, only spleen cells from vaccinated mice that were stimulated in vitro with TEV showed significant proliferation of CD3+/CD4+ and CD3+/CD8+ subpopulations and secreted significant amounts of interferon γ.ConclusionsTEV has surface amino groups that are available for chemical coupling. TEV induces both humoral and cellular responses when administered alone intraperitoneally to mice. Therefore, TEV should be evaluated as a vaccine adjuvant when chemically coupled to antigens of choice.

Self-assembly of hexahistidine-tagged tobacco etch virus capsid protein into microfilaments that induce IgG2-specific response against a soluble porcine reproductive and respiratory syndrome virus chimeric protein

“…The antibody response against TEV CP VLPs was determined as well (Additional file 1: Figure S1), with IgG1, IgG2a and IgG2b titers of 12500, 2500 and 2500, respectively. This antibody profile differs from the one that resulted after administering native TEV particles through the intraperitoneal route [5], where the subclass that presented the highest increase was IgG2a. The different immunization routes used might explain these results.…”

“…We previously attempted to explore the potential of Tobacco etch virus (TEV) particles as an adjuvant and our findings suggested that TEV induce both humoral and cellular response without the need of any other stimulus [5]. However, the use of plant viral infectious particles poses additional safety and environmental challenges [6].…”

Development of a Platform for Noncovalent Coupling of Full Antigens to Tobacco Etch Virus-Like Particles by Means of Coiled-Coil Oligomerization Motifs

“…The organization of coiled-coil motifs, flexible spacer, protein and His-tag in the amino acid sequences TEVK, GFPE-N and GFPE-C are shown in Figure 1 . Previous works suggest that the N-terminus of TEV CP is displayed on the surface of both viral particles and VLPs [ 22 , 23 ]. Additionally, a His-tag in the C-terminus of E. coli -expressed TEV CP enhances VLP recovery [ 24 ].…”

Plant Viruses as Adjuvants for Next-Generation Vaccines and Immunotherapy

“…The highest titres, after the immunisation of laboratory animals, were for the IgG2a isotype. In an experiment using cultured splenocytes, it was shown that TEV induced interferon γ (IFNγ) secretion [ 51 ]. This fact, in combination with high IgG2a titres, enables TEV to be regarded as an adjuvant capable of stimulating a Th1 response.…”