Taken together our observations show that a single neutralizing mAb from each of the three patients does not reflect the major neutralizing spectrum of the patients' plasma and there is no apparent correlation of the mAbs targeting HIV strains belonging to the subtype of virus infecting the patient. It is quite evident that different neutralization assays yield different results and it is still unclear which one is most predictive or suited to obtain neutralizing mAbs. Nevertheless, the strategy used for selection of plasma (in an extended incubation PBMC assay) and selection of mAb (based on ELISA binding and neutralizing capacity in a HOS_PV assay) yielded interesting new mAbs. A better understanding of in vitro neutralization characterizations of patient plasma and Abs and will hopefully lead to more effective ways of discovering new Abs that ultimately can be used for HIV-1 immunogen design and subsequent vaccine development. EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies. Epstein-Barr virus (EBV) is an almost ubiquitous human gamma herpes virus that infects resting human B-lymphocytes, including B-CLL cells, with high efficacy [1, 2] . EBV's B-cell tropism is mainly due to gp350, the viral envelope glycoprotein that interacts with the cellular complement receptor 2 (CR2, CD21) [3] on B cells. In EBV seropositive individuals, gp350 mainly elicits CD4+ T-cell responses [4] .