An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.

INTRODUCTION: Due to their faithful recapitulation of human disease, nonhuman primates (NHPs) are considered the gold standard for evaluating drugs against Ebolavirus and other filoviruses. The long-term goal is to reduce the reliance on NHPs with more ethical alternatives. In silico simulations and organoid models have the potential to revolutionize drug testing by providing accurate, human-based systems that mimic disease processes and drug responses without the ethical concerns associated with animal testing. However, as these emerging technologies are still in their developmental infancy, NHP models are presently needed for late-stage evaluation of filovirus vaccines and drugs, as they provide critical insights into the efficacy and safety of new medical countermeasures. AREAS COVERED: In this review, the authors introduce available NHP models and examine the existing literature on drug discovery for all medically significant filoviruses in corresponding models. EXPERT OPINION: A deliberate shift toward animal-free models is desired to align with the 3Rs of animal research. In the short term, the use of NHP models can be refined and reduced by enhancing replicability and publishing negative data. Replacement involves a gradual transition, beginning with the selection and optimization of better small animal models; advancing organoid systems, and using in silico models to accurately predict immunological outcomes.

Ebola-specific therapeutic antibodies from lab to clinic: The example of ZMapp.

In the 1990s, monoclonal antibodies (mAbs) progressed from scientific tools to advanced therapeutics, particularly for the treatment of cancers and autoimmune and inflammatory disorders. In the arena of infectious disease, the inauguration of mAbs as a post-exposure treatment in humans against Ebola virus (EBOV) occurred in response to the 2013-2016 West Africa outbreak. This review recounts the history of a candidate mAb treatment, ZMapp, beginning with its emergency use in the 2013-2016 outbreak and advancing to randomized controlled trials into the 2018-2020 African outbreak. We end with a brief discussion of the hurdles and promise toward mAb therapeutic use against infectious disease.

Medically Significant Vector-Borne Viral Diseases in Iran.

Vector-borne viral diseases (VBVDs) continue to pose a considerable public health risk to animals and humans globally. Vectors have integral roles in autochthonous circulation and dissemination of VBVDs worldwide. The interplay of agricultural activities, population expansion, urbanization, host/pathogen evolution, and climate change, all contribute to the continual flux in shaping the epidemiology of VBVDs. In recent decades, VBVDs, once endemic to particular countries, have expanded into new regions such as Iran and its neighbors, increasing the risk of outbreaks and other public health concerns. Both Iran and its neighboring countries are known to host a number of VBVDs that are endemic to these countries or newly circulating. The proximity of Iran to countries hosting regional diseases, along with increased global socioeconomic activities, e.g., international trade and travel, potentially increases the risk for introduction of new VBVDs into Iran. In this review, we examined the epidemiology of numerous VBVDs circulating in Iran, such as Chikungunya virus, Dengue virus, Sindbis virus, West Nile virus, Crimean-Congo hemorrhagic fever virus, Sandfly-borne phleboviruses, and Hantavirus, in relation to their vectors, specifically mosquitoes, ticks, sandflies, and rodents. In addition, we discussed the interplay of factors, e.g., urbanization and climate change on VBVD dissemination patterns and the consequent public health risks in Iran, highlighting the importance of a One Health approach to further surveil and to evolve mitigation strategies.

SARS-CoV-2 infection-induced immunity reduces rates of reinfection and hospitalization caused by the Delta or Omicron variants.

During a pandemic, effective vaccines are typically in short supply, particularly at onset intervals when the wave is accelerating. We conducted an observational, retrospective analysis of aggregated data from all patients who tested positive for SARS-CoV-2 during the waves caused by the Delta and Omicron variants, stratified based on their known previous infection and vaccination status, throughout the University of Texas Medical Branch (UTMB) network. Next, the immunity statuses within each medical parameter were compared to naïve individuals for the effective decrease of occurrence. Lastly, we conducted studies using mice and pre-pandemic human samples for IgG responses to viral nucleocapsid compared to spike protein toward showing a functional component supportive of the medical data results in relation to the immunity types. During the Delta and Omicron waves, both infection-induced and hybrid immunities were associated with a trend of equal or greater decrease of occurrence than vaccine-induced immunity in hospitalizations, intensive care unit admissions, and deaths in comparison to those without pre-existing immunity, with hybrid immunity often trending with the greatest decrease. Compared to individuals without pre-existing immunity, those vaccinated against SARS-CoV-2 had a significantly reduced incidence of COVID-19, as well as all subsequent medical parameters. Though vaccination best reduces health risks associated with initial infection toward acquiring immunity, our findings suggest infection-induced immunity is as or more effective than vaccination in reducing the severity of reinfection from the Delta or Omicron variants, which should inform public health response at pandemic onset, particularly when triaging towards the allotment of in-demand vaccinations.

Rhesus macaques show increased resistance to repeated SHIV intrarectal exposure following a heterologous regimen of rVSV vector vaccine expressing HIV antigen.

Despite the human immunodeficiency virus (HIV) pandemic continuing worldwide for 40 years, no vaccine to combat the disease has been licenced for use in at risk populations. Here, we describe a novel recombinant vesicular stomatitis virus (rVSV) vector vaccine expressing modified HIV envelope glycoproteins and Ebola virus glycoprotein. Three heterologous immunizations successfully prevented infection by a different clade SHIV in 60% of non-human primates (NHPs). No trend was observed between resistance and antibody interactions. Resistance to infection was associated with high proportions of central memory T-cell CD69 and CD154 marker upregulation, increased IL-2 production, and a reduced IFN-γ response, offering insight into correlates of protection.

SARS-CoV-2 molecular diagnosis at airports to minimize travel-related COVID-19 spread.

Following the identification of SARS-CoV-2, screening for air travel helped mitigate spread, yet lessons learned from a case study of air travel within Canada display enhanced techniques to better identify infected individuals, informing future responsive screening. While international travel bans limit infectious spread beyond a country's borders, such measures are hardly sustainable economically and infrequently address domestic travel. Here, we describe a case study from Canada, where a diagnostic laboratory at point of travel conducted real-time PCR-based detection of SARS-CoV-2 in support of existing interventions, including clinical and epidemiological questionnaires, and temperature checks. All mining workers departing from a populated urban area flying to one of two sites (Site A and B) in a remote northern Canadian region, which we deemed "at-risk", because healthcare services are limited and vulnerable to epidemics. Data collected between June and November 2020 on 15,873 clinical samples, indicate that molecular diagnosis allowed for identification of 13 infected individuals, who would have otherwise been missed by using solely nonpharmaceutical interventions. Overall, no outbreaks, COVID-19-related or other, were detected at the point of travel up to December 2021 since the implementation of the laboratory, suggesting this screening process is an effective means to protect at-risk communities. The success of this study suggests a process more practical than travel bans or an unfocused screening of air travelers everywhere.

A novel intradermal tattoo-based injection device enhances the immunogenicity of plasmid DNA vaccines.

In recent years, tattooing technology has shown promising results toward evaluating vaccines in both animal models and humans. However, this technology has some limitations due to variability of experimental evaluations or operator procedures. The current study evaluated a device (intradermal oscillating needle array injection device: IONAID) capable of microinjecting a controlled dose of any aqueous vaccine into the intradermal space. IONAID-mediated administration of a DNA-based vaccine encoding the glycoprotein (GP) from the Ebola virus resulted in superior T- and B-cell responses with IONAID when compared to single intramuscular (IM) or intradermal (ID) injection in mice. Moreover, humoral immune responses, induced after IONAID vaccination, were significantly higher to those obtained with traditional passive DNA tattooing in guinea pigs and rabbits. This device was well tolerated and safe during HIV vaccine delivery in non-human primates (NHPs), while inducing robust immune responses. In summary, this study shows that the IONAID device improves vaccine performance, which could be beneficial to the animal and human health, and importantly, provide a dose-sparing approach (e.g., monkeypox vaccine).