Abstract
BackgroundHuman endogenous retroviruses (HERVs) are remnants of ancestral infections and chromosomally integrated in all cells of an individual, are transmitted only vertically and are defective in viral replication. However enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed inter-alia in HIV-infected individuals and tumor patients. Therefore HERV-K might serve as a tumor-specific antigen or even as a constant target for the development of an HIV vaccine.ResultsTo verify our hypothesis, we tested the immunogenicity of HERV-K Gag by using a recombinant vaccinia virus (MVA-HKcon) expressing the HERV-K Gag protein and established an animal model to test its vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) and the HERV-K Gag protein (RLZ-HKGag cells). Subcutaneous application of RLZ-HKGag cells into syngenic BALB/c mice resulted in the formation of local tumors in MVA vaccinated mice. MVA-HKcon vaccination reduced the tumor growth. Furthermore, intravenous injection of RLZ-HKGag cells led to the formation of pulmonary metastases. Vaccination of tumor-bearing mice with MVA-HKcon drastically reduced the number of pulmonary RLZ-HKGag tumor nodules compared to vaccination with wild-type MVA.ConclusionThe data demonstrate that HERV-K Gag is a useful target for vaccine development and might offer new treatment opportunities for cancer patients.
Highlights
Human endogenous retroviruses (HERVs) are remnants of ancestral infections and chromosomally integrated in all cells of an individual, are transmitted only vertically and are defective in viral replication
Establishment of an animal model and the experimental vaccine The development of HERV-K-specific vaccines is hampered by the availability of an appropriate animal model because HERV-K is exclusively expressed in humans
Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) [10] and the HERVK Gag gene was introduced by retroviral transduction (RLZ-HKGag cells)
Summary
Human endogenous retroviruses (HERVs) are remnants of ancestral infections and chromosomally integrated in all cells of an individual, are transmitted only vertically and are defective in viral replication. HERV-K might serve as a tumor-specific antigen or even as a constant target for the development of an HIV vaccine. HERVs are relics of ancient viral infections events into the germ line and are since transmitted vertically. These retrovirus genomes are chromosomally integrated in all cells of an individual and their sequences comprise about 8% of the human genome. Tumor-associated antigens (TAAs), proteins expressed mainly or exclusively by tumor cells, can be used for therapeutic vaccinations, in particular for the treatment of minimal residual disease. Recombinant poxviruses are frequently used as vaccine vectors, because they activate robust cellular MHC class Iand II-restricted CD8+ and CD4+ T cell responses against recombinant antigens [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
