Adenoviral (Ad) vectors represent promising vaccine platforms for infectious disease. To overcome pre-existing immunity to commonly used human adenovirus serotype 5 (Ad5), vectors based on rare species or non-human Ads are being developed. However, these vectors often exhibit reduced potency compared with Ad5, necessitating the use of innovative approaches to augment the immunogenicity of the encoded antigen (Ag). To achieve this, we engineered model Ag, enhanced green fluorescent protein (EGFP), for targeting to the surface of host-derived extracellular vesicles (EVs), namely exosomes. Exosomes are nano-sized EVs that play important roles in cell-to-cell communication and in regulating immune responses. Directed targeting of Ag to the surface of EVs/exosomes is achieved by "exosome display," through fusion of Ag to the C1C2 domain of lactadherin, a protein highly enriched in exosomes. Herein, we engineered chimpanzee adenovirus ChAdOx1 and Ad5based vaccines encoding EGFP, or EGFP targeted to EVs (EGFP_C1C2), and compared vaccine immunogenicity in mice. We determined that exosome display substantially increases Ag-specific humoral immunity following intramuscular and intranasal vaccination, improving the immunological potency of both ChAdOx1 and Ad5. We propose that this Agengineering approach could increase the immunogenicity of diverse Ad vectors that exhibit desirable manufacturing characteristics, but currently lack the potency of Ad5.

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Blood samples from 13 locations in the Pacific and South-East Asia were tested for evidence of infection with human T-cell lymphotropic virus type-1 (HTLV-1), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) and hepatitis delta virus (HDV). No samples were positive for antibody to HIV-1. Antibodies to HTLV-1 were found in samples from five locations, the maximum prevalence being 19%, in Vanuatu. Serological markers of HBV infection were found in all locations, the maximal prevalence being 88%, in Majuro, Micronesia. Antibodies to HDV in HBsAg positive sera were found in six locations with a maximum prevalence of 81% in Kiribati.

We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells. Adoptive transfer of CD8 T cells, alone or together with CD4 T cells or natural killer cells, from LV305-immunized donor mice to tumor-bearing recipient mice conferred significant protection against metastatic tumor growth. Biodistribution of injected LV305 in mice was limited to the site of injection and the draining lymph node, and injected LV305 exhibited minimal excretion. Mice injected with LV305 developed little to no adverse effects, as evaluated by toxicology studies adherent to good laboratory practices. Taken together, these data support the development of LV305 as a clinical candidate for treatment against tumors expressing NY-ESO-1.

Central venous catheters (CVCs) are often used in intensive care units and operating rooms. They facilitate hemodynamic monitoring, administration of fluids and medications, transvenous pacing and renal fluid replacement therapy. Severe complications can arise from inserting CVCs, some of which may be life threatening. A safe insertion technique with confirmation of correct placement of these catheters is of utmost importance. We present an obese 66-yr-old man who had carotid artery dissection with compromised cerebral circulation after CVC insertion under ultrasound guidance. The dissection was immediately repaired with no neurological sequelae to the patient.