A Single Vaccination with Polyomavirus VP1/VP2Her2 Virus-Like Particles Prevents Outgrowth of HER-2/neu–Expressing Tumors

Abstract

Murine polyomavirus (MPyV) VP1 virus-like particles (VLPs), containing a fusion protein between MPyV VP2 and the extracellular and transmembrane domain of HER-2/neu (Her2), Her2 1-683 PyVLPs, were tested for their ability to vaccinate against Her2-expressing tumors in two different in vivo models. Protection was assessed both against a lethal challenge with a BALB/c mammary carcinoma transfected with human Her2 (D2F2/E2) and against the outgrowth of autochthonous mammary carcinomas in BALB-neuT mice, transgenic for the activated rat Her2 oncogene. A single injection of Her2 1-683 PyVLPs before tumor inoculation induced a complete rejection of D2F2/E2 tumor cells in BALB/c mice. Similarly, a single injection of Her2 1-683 PyVLPs at 6 weeks of age protected BALB-neuT mice with atypical hyperplasia from a later outgrowth of mammary carcinomas, whereas all controls developed palpable tumors in all mammary glands. VLPs containing only VP1 and VP2 did not induce protection. The protection elicited by Her2 1-683 PyVLPs vaccination was most likely due to a cellular immune response because a Her2-specific response was shown in an ELISPOT assay, whereas antibodies against Her2 were not detected in any of the two models. The results show the feasibility of using MPyV-VLPs carrying Her2 fusion proteins as safe and efficient vaccines against Her2-expressing tumors. (Cancer Res 2005; 65(13): 5953-7)

Bcr-Abl fusion sequences do not induce immune responses in mice when administered in mouse polyomavirus based virus-like particles

“…Similar findings were obtained with MPy VLPs carrying EGFP in our previous study (20) or the Her2/neu epitope (17). We detected very low presence of neutralizing antibodies against VP1 protein in the sera of intranasally immunized mice (20) suggesting the possibility of repeating administration of chimeric VLPs containing 'hidden' antigen without being neutralized.…”

“…The ratio of intensities of VP1 and Bcr-Abl 171 -tVP3 bands on SDS PAGE suggests that average number of the epitope molecules in one particle is 11-12. Tegerstedt et al (17) found morphology of MPy VLPs carrying 683 amino acid long Her2/neu connected with the entire VP2, the longer one of two minor capsid proteins, not affected. However, the estimated number of Her2/neu molecules per 1 particle was very low (3 molecules per VLP).…”

“…However, the estimated number of Her2/neu molecules per 1 particle was very low (3 molecules per VLP). Surprisingly, these chimeric particles were able to efficiently protect Balb/c mice from outgrowth of the Her2 expressing tumor (17).…”

“…Furthermore, exploitation of MPyV-VLPs as carriers of foreign epitopes has been examined. Several types of chimeric VLPs were prepared and used in different immunization protocols (17)(18)(19). In some studies, the short epitopes were exposed on the surface of the particle by insertion into the surface loops of the major structural protein VP1.…”

HER2/neu: an increasingly important therapeutic target. Part 1: basic biology & therapeutic armamentarium

“…Viral vector vaccine strategies using adenovirus vectors [257][258][259][260], alphavirus vectors [212,213,261], vaccinia virus vectors (NCT00485277 and NCT01152398), vesicular stomatitis virus [262] and polyoma virus systems [263,264] have all been used to elicit anti-HER2/neu immune responses. The intracellular bacteria Listeria monocytogenes has also been adapted as an immunotherapeutic vector system and studied in strategies to elicit anti-HER2/neu immune responses [215,265].…”