Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously

Abstract

With the aim to improve the efficacy of therapeutic vaccines that target self-antigens, we have developed a novel fusion protein vaccine on the basis of the C-terminal multimerizing end of the variable lymphocyte receptor B (VLRB), the Ig equivalent in jawless fishes. Recombinant vaccines were produced in by fusing the VLRB sequence to 4 different cancer-associated target molecules. The anti-self-immune response generated in mice that were vaccinated with VLRB vaccines was compared with the response in mice that received vaccines that contained bacterial thioredoxin (TRX), previously identified as an efficient carrier. The anti-self-Abs were analyzed with respect to titers, binding properties, and duration of response. VLRB-vaccinated mice displayed a 2- to 10-fold increase in anti-self-Ab titers and a substantial decrease in Abs against the foreign part of the fusion protein compared with the response in TRX-vaccinated mice ( < 0.01). VLRB-generated Ab response had duration similar to the corresponding TRX-generated Abs, but displayed a higher diversity in binding characteristics. Of importance, VLRB vaccines could sustain an immune response against several targets simultaneously. VLRB vaccines fulfill several key criteria for an efficient therapeutic vaccine that targets self-antigens as a result of its small size, its multimerizing capacity, and nonexposed foreign sequences in the fusion protein.-Saupe, F., Reichel, M., Huijbers, E. J. M., Femel, J., Markgren, P.-O., Andersson, C. E., Deindl, S., Danielson, U. H., Hellman, L. T., Olsson, A.-K. Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously.

Characterization of Hagfish (Eptatretus burgeri) Variable Lymphocyte Receptor–Based Antibody and Its Potential Role in the Neutralization of Nervous Necrosis Virus

“…The monomeric VLR67 and VLR76 migrated as monomeric units at approximately ∼ 40 kDa under both nonreducing and reducing conditions, and these monovalent VLRBs showed no reactivity to the Ags, NNV, VHSV, and AIV, as expected ( Fig. 1D) (27,28). These results indicated that the Ag binding ability of the multimerized form of VLRBs was much higher than that of monomeric VLRBs.…”

Cancer Vaccination against Extracellular Vimentin Efficiently Adjuvanted with Montanide ISA 720/CpG

“…This approach makes use of conjugation of the target of interest to a foreign protein, such as the truncated form of bacterial thioredoxin (TRXtr) [ 10 ]. The conjugate vaccine technology has been shown to efficiently induce an antibody-based immune response against vascular-specific self-proteins [ 7 , 8 , 10 , 11 , 12 ]. It is important to mention that in addition to an efficient immunization strategy, the co-administration of a potent adjuvant is needed to generate this immune response.…”

The variable lymphocyte receptor as an antibody alternative

“…To this end, the C-terminal multimerizing end of VLRB was fused to cancer relevant vaccine targets, creating a multimeric vaccine with minimal exposed VLR sequence. These properties resulted in a more effective vaccine with higher Ab titer against the vaccine target and lower Ab titer against the VLR component compared with other carrier strategies [44].…”