The vertebrate blood–brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter. In this review, we discuss evidence for the existence of brain vascular heterogeneity, focusing on differences between the vessels of the grey and white matter. The region-specific differences in the vasculature of the brain are reflective of specific functions of those particular brain areas. This BBB-endothelial heterogeneity may have implications for the course of pathogenesis of cerebrovascular diseases and neurological disorders involving vascular activation and dysfunction. This heterogeneity should be taken into account when developing BBB-neuro-disease models representative of specific brain areas.

Zika virus’s (ZIKV) emergence as a pathogen of significant public health importance has accelerated efforts to develop a ZIKV vaccine. To date, the need for an effective ZIKV vaccine is unmet. In this study, we report inactivation of ZIKV using a hydrophobic photoactive compound: 1, 5 iodonaphthyl azide (INA). 50 and 100 µM of INA completely inactivated ZIKV (INA-ZIKV). Western blot and ELISA analysis show some loss of the binding capacity of INA-iZIKV to anti-ZIKV monoclonal antibodies; however, immunization of mice with INA-iZIKV demonstrated seroconversion and ZIKV-neutralizing antibody response. RNA isolated from INA-iZIKV did not induce productive infection in Vero cells, suggesting inactivation of ZIKV RNA. These results suggest that in the absence of an approved ZIKV vaccine, INA-iZIKV can be pursued as a viable ZIKV vaccine candidate.

Mayaro virus (MAYV) is an emerging alphavirus in the family Togaviridae that causes a self-limited febrile illness accompanied by maculopapular rash and arthralgia. MAYV is reported throughout South America and the Caribbean and has potential to cause widespread outbreaks. There is no FDA-approved vaccine for MAYV. The overall objectives of this study were to inactivate MAYV utilizing various inactivation approaches, and to identify a highly safe vaccine candidate with optimum immunogenicity. MAYV was inactivated by three different mechanisms: formalin; 1, 5 iodonaphthyl azide (INA); and γ-radiation. Formalin inactivation (F-iMAYV) was performed with 0.05 or 0.1% formalin at 35°C. INA-inactivation (INA-iMAYV) was performed with 10, 50, or 100 μM INA combined with UV exposure. Lastly, MAYV was inactivated with 10, 20, or 30 kGy of γ-radiation in the presence of a protein-protecting manganese-decapeptide-phosphate complex (MDP-iMAYV). MAYV was inactivated by all the three approaches. Dose- and incubation time-dependent effects were observed with formalin inactivation. 0.1% formalin with an incubation time of 48h inactivated MAYV; however, further evaluation is ongoing. MAYV was completely inactivated with >50 μM dose of INA and by all three doses of γ-radiation. Differential protection of MAYV epitopes was observed after inactivation with three agents and with different doses of the inactivating agent. The most consistent antigen (Ag)-antibody (Ab) binding was observed in INA-iMAYV, followed by MDP-iMAYV. Ag-Ab binding was almost completely lost in F-iMAYV. The data suggests that INA and MDP-inactivated MAYV can be further studied as vaccine candidates. Studies are planned to evaluate immunogenicity in-vivo.

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