Competing Responses to Global Inequalities in Access to COVID Vaccines: Vaccine Diplomacy and Vaccine Charity Versus Vaccine Liberty.

Global access to coronavirus vaccines has been extraordinarily unequal and remains an ongoing source of global health insecurities from the evolution of viral variants in the bodies of the unvaccinated. There have nevertheless been at least 3 significant alternatives developed to this disastrous bioethical failure. These alternatives are reviewed in this article in the terms of "vaccine diplomacy," "vaccine charity," and "vaccine liberty." Vaccine diplomacy includes the diverse bilateral deliveries of vaccines organized by the geopolitical considerations of countries strategically seeking various kinds of global and regional advantages in international relations. Vaccine charity centrally involves the humanitarian work of the global health agencies and donor governments that have organized the COVAX program as an antidote to unequal access. Despite their many promises, however, both vaccine diplomacy and vaccine charity have failed to deliver the doses needed to overcome the global vaccination gap. Instead, they have unfortunately served to immunize the global vaccine supply system from more radical demands for a "people's vaccine," technological transfer, and compulsory licensing of vaccine intellectual property (IP). These more radical demands represent the third alternative to vaccine access inequalities. As a mix of nongovernmental organization-led and politician-led social justice demands, they are diverse and multifaceted, but together they have been articulated as calls for vaccine liberty. After first describing the realities of vaccine access inequalities, this article compares and contrasts the effectiveness thus far of the 3 alternatives. In doing so, it also provides a critical bioethical framework for reflecting on how the alternatives have come to compete with one another in the context of the vaccine property norms and market structures entrenched in global IP law. The uneven and limited successes of vaccine diplomacy and vaccine charity in delivering vaccines in underserved countries can be reconsidered in this way as compromised successes that not only compete with one another, but that have also worked together to undermine the promise of universal access through vaccine liberty.

Complete Genome Sequence of the First Camelpox Virus Case Diagnosed in Israel.

We report here the whole-genome sequence of the first camelpox virus case diagnosed in Israel. The strain (Negev2016) was isolated in 2016 from a camel in southern Israel and was sequenced on the Illumina MiSeq and Oxford Nanopore MinION platforms.

First Diagnosed Case of Camelpox Virus in Israel.

An outbreak of a disease in camels with skin lesions was reported in Israel during 2016. To identify the etiological agent of this illness, we employed a multidisciplinary diagnostic approach. Transmission electron microscopy (TEM) analysis of lesion material revealed the presence of an orthopox-like virus, based on its characteristic brick shape. The virus from the skin lesions successfully infected chorioallantoic membranes and induced cytopathic effect in Vero cells, which were subsequently positively stained by an orthopox-specific antibody. The definite identification of the virus was accomplished by two independent qPCR, one of which was developed in this study, followed by sequencing of several regions of the viral genome. The qPCR and sequencing results confirmed the presence of camelpox virus (CMLV), and indicated that it is different from the previously annotated CMLV sequence available from GenBank. This is the first reported case of CMLV in Israel, and the first description of the isolated CMLV subtype.

Highly Stable Lyophilized Homogeneous Bead-Based Immunoassays for On-Site Detection of Bio Warfare Agents from Complex Matrices.

This study shows the development of dry, highly stable immunoassays for the detection of bio warfare agents in complex matrices. Thermal stability was achieved by the lyophilization of the complete, homogeneous, bead-based immunoassay in a special stabilizing buffer, resulting in a ready-to-use, simple assay, which exhibited long shelf and high-temperature endurance (up to 1 week at 100 °C). The developed methodology was successfully implemented for the preservation of time-resolved fluorescence, Alexa-fluorophores, and horse radish peroxidase-based bead assays, enabling multiplexed detection. The multiplexed assay was successfully implemented for the detection of Bacillus anthracis, botulinum B, and tularemia in complex matrices.

Ready to benefit from training: heterologous effects of early life immunization.

Trained immunity reflects the ability of the innate immune system to adapt via epigenetic changes in monocytes, enhancing responses to a range of microbes, thereby potentially reducing infection in high-risk populations. Examples of trained immunity at birth include enhanced resistance to infection in TLR-simulated newborn mice, reduced risk of late onset sepsis with histologic chorioamnionitis and beneficial heterologous effects of neonatal bacille Calmette-Guérin administration in reducing diverse infections during infancy. Future efforts will assess leveraging trained immunity in early life by administering 'stand-alone' innate immune stimuli or (self-)adjuvanted vaccines to protect against a broad range of infections.

Establishment of cell-based reporter system for diagnosis of poxvirus infection.

Poxvirus detection assays are based on morphology, viral antigens and specific nucleic acids, none of which indicates virus viability or infectious capacity. Determination of virus viability is achieved by propagation in cell cultures and subsequent analysis by the mentioned methods, a process that takes days. Thus, presented here the development of a new assay, named PILA (Poxvirus Infection Luciferase Assay), for rapid detection of infectious poxviruses which is a cell-based reporter assay. The assay is composed of two steps: (i) Transfection of cells with a poxvirus specific reporter vector which consists of the early 7.5-kDa-STR promoter, regulating the expression of luciferase gene; (ii) Infection with a poxvirus containing sample. Luciferase activity measured post infection, indicates the presence of infectious poxvirus in the sample. The assay can detect quantities as low as 100 PFU of VACV, six hours post infection. Orthopox virus universality was confirmed by detection of various Orthopoxviruses, and specificity was verified by using pox-specific neutralizing antibodies. The PILA is specific, rapid, simple, and suitable for detecting viable virus. The assay can be utilized for applications such as poxvirus titration, neutralizing assay and drug discovery. The assay was adjusted for live detection assay by using GFP as reporting gene.

The transcription of the hGnRH-I and hGnRH-II genes in human neuronal cells is differentially regulated by estrogen.

Gonadotropin releasing hormone-I (GnRH-I), a decapeptide serves as a key regulator of reproduction. Recently, several groups have identified in the mammalian brain a second form of GnRH, of unknown function, designated GnRH-II. The human neuronal medulloblastoma cells (TE-671) were recently demonstrated to express the two forms of GnRH (GnRH-I and GnRH-II). We used this cell line, as a model system, to investigate the regulation of human GnRH-I and GnRH-II genes by estrogen. Estrogen is one of the principal regulators of GnRH-I in hypothalamic neurons, acting as a classic homeostatic feedback molecule between the gonads and the brain. In this study, we investigated the regulation of the two GnRH forms by estrogen, in the human neuronal cell line TE-671. We demonstrate, for the first time, that the hGnRH-II and hGnRH-I genes are differentially regulated by estrogen. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern hybridization, we found that estrogen increases endogenous hGnRH-II mRNA levels and decreases endogenous hGnRH-I mRNA levels. Furthermore, we found these effects to be promoter-mediated. We cloned the hGnRH-I and hGnRH-II promoter constructs upstream to a luciferase reporter plasmid, and cotransfected these constructs with an estrogen receptor alpha into the TE-671 neuronal cells. Luciferase activity of GnRH promoter constructs treated with estrogen demonstrates that the differential regulation of the GnRH genes by estrogen is mediated at the transcription level.