Our structural analysis shows that specific antibodies or other ligands directed against the 12 amino acid insertion would be able to readily bind without stearic hindrance. This unique peptide that is exposed on the surface of the HBV/G core could be exploited as a possible site for epitope presentation in an HBcAg core-based vaccine. Because HBV/G already has an insertion in the N-terminus, it may tolerate even larger insertions than have been tried previously in HBV/A cores, while still maintaining the ability for efficient self-assembly. In addition, the possibility of detecting specific antibodies directed against the insertion peptide in sera from patients infected with HBV/G could be explored. Such testing might help to resolve the issue of whether HBV/G can replicate in vivo in the absence of a helper virus strain and would assist in diagnosing patients infected with HBV/G. In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization. Dengue virus (DENV) complex consists of 4 serotypes. People exposed to primary DENV infections develop robust antibody responses that cross-react with all serotypes (Reviewed in [1] ). Despite the extensive cross-reactivity, individuals only develop long term, protective immunity against the homologous serotype responsible for the primary infection [2, 3] . Indeed, the risk of progressing to DHF is greater during secondary compared to primary infection [4] . A prevailing theory that explains severe dengue during secondary infection is that pre-existing, non-neutralizing dengue specific antibodies enhance DENV entry and replication in Fc-receptor-bearing cells, which leads to a higher viremia and more severe disease [4] . Antibodies have been demonstrated to enhance DENV in cell culture [5, 6] and in animal models of dengue pathogenesis [7] [8] [9] .