Immune Response to Chikungunya Virus: Sex as a Biological Variable and Implications for Natural Delivery via the Mosquito.

Chikungunya virus (CHIKV) is a mosquito-borne virus with significant public health implications around the world. Climate change, as well as rapid urbanization, threatens to expand the population range of vector mosquitoes globally, increasing CHIKV cases worldwide in return. Epidemiological data suggests a sex-dependent response to CHIKV infection.

Tick-Borne Pathogens Associated with Medically Important Ticks in Alabama: A Four-Year Survey.

Tick-borne diseases (TBDs) represent a significant threat to human health in the United States. Based on reported cases of notifiable TBDs to the Centers for Disease Control and Prevention (CDC) the state of Alabama is no exception, yet previously there has been no active surveillance program in place to comprehensively assess the presence and prevalence of tick vectors and their associated TBD pathogens in Alabama. Here we summarize initial findings from a 4-year survey to address this unmet need.

Statewide survey of medically important ticks on white-tailed deer, Zimmerman, in Alabama, U.S.A.

A statewide survey of the tick fauna found on deer, using harvested deer heads as the sample unit, was conducted during the Alabama hunting seasons of 2019-2020 and 2020-2021. Four species of ticks: (n= 936, % of catch 69.1%), (315, 23.

Ticks of Alabama: the fauna and spatial distribution of medically important species across the state.

The last statewide survey of hard ticks in Alabama was in 1972. To address this deficit, we examined the distribution of the medically important species across the state, (Say), (Say), (L.), and (Koch), between April, 2018 and February, 2021.

Real-time tracking of bioluminescent influenza A virus infection in mice.

Despite the availability of vaccines and antiviral therapies, seasonal influenza infections cause 400,000 human deaths on average per year. Low vaccine coverage and the occurrence of drug-resistant viral strains highlight the need for new and improved countermeasures. While influenza A virus (IAV) engineered to express a reporter gene may serve as a valuable tool for real-time tracking of viral infection, reporter gene insertion into IAV typically attenuates viral pathogenicity, hindering its application to research.

AR12 (OSU-03012) suppresses GRP78 expression and inhibits SARS-CoV-2 replication.

AR12 is a derivative of celecoxib which no-longer acts against COX2 but instead inhibits the ATPase activity of multiple chaperone proteins, in particular GRP78. GRP78 acts as a sensor of endoplasmic reticulum stress and is an essential chaperone required for the life cycle of all mammalian viruses. We and others previously demonstrated in vitro and in vivo that AR12 increases autophagosome formation and autophagic flux, enhances virus protein degradation, preventing virus reproduction, and prolonging the survival of infected animals.

Comparative pathology study of Venezuelan, eastern, and western equine encephalitis viruses in non-human primates.

Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) are mosquito-borne viruses in the Americas that cause central nervous system (CNS) disease in humans and equids. In this study, we directly characterized the pathogenesis of VEEV, EEEV, and WEEV in cynomolgus macaques following subcutaneous exposure because this route more closely mimics natural infection via mosquito transmission or by an accidental needle stick. Our results highlight how EEEV is significantly more pathogenic compared to VEEV similarly to what is observed in humans.

Single dose of DPX-rPA, an enhanced-delivery anthrax vaccine formulation, protects against a lethal spore inhalation challenge.

Anthrax is a serious biological threat caused by pulmonary exposure to aerosolized spores of . Biothrax (anthrax vaccine adsorbed (AVA)) is the only Food and Drug Administration-licensed vaccine and requires five administrations over 12 months with annual boosting to maintain pre-exposure prophylaxis. Here we report the evaluation of a single intramuscular injection of recombinant -protective antigen (rPA) formulated in the DPX delivery platform.

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque's and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge.

Development of a Zika Virus Infection Model in Cynomolgus Macaques.

Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates.

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus.

Despite the rapid spread of Zika virus (ZIKV) infection and associated neurological complications in the America's, prophylactic or therapeutic countermeasures are not currently available. This is mostly due to the fact that until recently there was no presumed need for medical intervention since there was no association between ZIKV infection and significant human morbidity. Consequently, there are currently no tools due mostly to the lack of sensitive cell based assays amenable for identification of ZIKV inhibitors.

Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales.

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses.

Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses.

Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice.

Gas-permeable ethylene bags for the small scale cultivation of highly pathogenic avian influenza H5N1 and other viruses in embryonated chicken eggs.

Background: Embryonated chicken eggs (ECE) are sometimes used for the primary isolation or passage of influenza viruses, other viruses, and certain bacteria. For small-scale experiments with pathogens that must be studied in biosafety level three (BSL3) facilities, inoculated ECE are sometimes manipulated and maintained in small egg incubators within a biosafety cabinet (BSC). To simplify the clean up and decontamination of an egg incubator in case of egg breakage, we explored whether ethylene breather bags could be used to encase ECE inoculated with pathogens.

Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1.

Analysis of Venezuelan equine encephalitis replicon particles packaged in different coats.

Background: The Venezuelan equine encephalitis (VEE) virus replicon system was used to produce virus-like replicon particles (VRP) packaged with a number of different VEE-derived glycoprotein (GP) coats. The GP coat is believed to be responsible for the cellular tropism noted for VRP and it is possible that different VEE GP coats may have different affinities for cells. We examined VRP packaged in four different VEE GP coats for their ability to infect cells in vitro and to induce both humoral and cellular immune responses in vivo.

A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques.

A candidate vaccine (D1ME-VRP) expressing dengue virus type 1 premembrane and envelope proteins in a Venezuelan equine encephalitis (VEE) virus replicon particle (VRP) system was constructed and tested in conjunction with a plasmid DNA vaccine (D1ME-DNA) expressing identical dengue virus sequences. Cynomolgus macaques were vaccinated with three doses of DNA (DDD), three doses of VRP (VVV group), or a heterologous DNA prime-VRP boost regimen (DDV) using two doses of DNA vaccine and a third dose of VRP vaccine. Four weeks after the final immunization, the DDV group produced the highest dengue virus type 1-specific immunoglobulin G antibody responses and virus-neutralizing antibody titers.

Uncommon respiratory pathogens.

Purpose Of Review: In many cases, the specific pathogen responsible for a respiratory infection is not identified and can lead to improper medical treatment, increased duration of illness, and possibly contributes to the development of antibiotic resistance. Molecular-based diagnostic methodologies have significantly improved our ability to identify common respiratory pathogens; these techniques are not useful, however, when a novel pathogen is responsible for the infection and clinicians must rely on differential diagnosis for the treatment of patients.

Recent Findings: New pathogens previously not associated with human infections have been identified in the past few years.

Venezuelan equine encephalitis replicon immunization overcomes intrinsic tolerance and elicits effective anti-tumor immunity to the 'self' tumor-associated antigen, neu in a rat mammary tumor model.

Many tumor-associated antigens (TAAs) represent 'self' antigens and as such, are subject to the constraints of immunologic tolerance. There are significant barriers to eliciting anti-tumor immune responses of sufficient magnitude. We have taken advantage of a Venezuelan equine encephalitis-derived alphavirus replicon vector system with documented in vivo tropism for immune system dendritic cells.

Alphavirus vectors and vaccination.

Alphaviruses are positive-stranded RNA viruses that have a broad host range and therefore are capable of replicating in many vertebrate and invertebrate cells. The single-stranded alphavirus genome is divided into two ORFs. The first ORF encodes the nonstructural proteins that are translated upon entry of the virus into the cytoplasm and are responsible for transcription and replication of viral RNA.