bThree variants of the major rubella virus (RV) E1 protein virus-neutralizing epitope from position 214 to 285 were exposed on the hepatitis B virus (HBV) C-terminally truncated core (HBc⌬) in a virus-like particle (VLP) vector and were produced in Escherichia coli. All three chimeras demonstrated VLPs in bacterial cell lysates, but only HBc⌬-E1(245-285) demonstrated the correct VLP structure after purification. The other chimeras, HBc⌬-E1(214-285) and HBc⌬-E1(214-240), appeared after purification as non-VLP aggregates of 100 to 900 nm in diameter according to dynamic light scattering data. All three variants possessed the intrinsic antigenic activity of RV E1, since they were recognized by natural human anti-RV E1 antibodies and induced an anti-RV E1 response in mice. HBc⌬-E1(214-240) and HBc⌬-E1(245-285) can be regarded as prototypes for a putative RV vaccine because they were able to induce antibodies recognizing natural RV E1 protein in RV diagnostic kits. R ubella virus (RV) is an enveloped, positive single-stranded RNA virus and a member of the genus Rubivirus, which belongs to the Togaviridae family. Rubella is normally a mild, selflimited disease but may cause fetal damage if it is acquired during the first trimester of pregnancy. In this case, congenital rubella syndrome could be generated in infants after birth (for a review, see reference 1). One of the most widely used RV vaccines, Meruvax, is a live attenuated vaccine that was propagated using the human cell line WI-38, which was derived from embryonic lung tissue in 1961 (2, 3), and is used as a component of the mixed measles, mumps, and rubella (MMR) vaccine (for a review, see reference 4). Because of the drawbacks of human cell line-derived vaccines, there is an urgent need for the construction of recombinant RV vaccine candidates.RV consists of three structural proteins: a capsid protein and two membrane-spanning glycoproteins, E1 and E2, localized in the virus envelope (5). E1 is the dominant surface molecule of the virus particle; it represents the main target for the detection and subsequent elimination of RV by the host's immune system (6, 7). Immunoprecipitation or immunoblot techniques have shown that most of the anti-RV immunoglobulin response seems to be induced by the E1 glycoprotein. Although both E1 and E2 provide lifelong immunity, the hemagglutination activity and viral neutralization activity have been attributed to the E1 protein at amino acid positions 208 to 239 (7, 8), 213 to 239 (9), and 214 to 240 (10). Three additional neutralizing and hemagglutination epitopes have been identified within the E1 glycoprotein between residues 245 and 285 (11). Therefore, these E1 protein epitopes may have potential not only in diagnostics but also in the development of vaccines against RV infection (12).The hepatitis B virus (HBV) core (HBc) protein was first reported as a promising virus-like particle (VLP) carrier in 1986 (13), and this was published in 1987 (14, 15). In many ways, HBc maintains a unique position among other VLP carriers be...