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•A single dose of CHIKV/IRES vaccine elicits neutralizing antibody and virus-specific T cell responses.•CHIKV/IRES immune CD4+ or CD8+ T cells do not protect A129 mice against CHIKV-LR challenge.•A correlate of a neutralizing antibody titer and protection has been established. Chikungunya virus (CHIKV), a mosquito-borne alphavirus, recently re-emerged in Africa and spread to islands in the Indian Ocean, the Indian subcontinent, and to South East Asia. Viremic travelers have also imported CHIKV to the Western hemisphere highlighting the importance of CHIKV in public health. In addition to the great burden of arthralgic disease, which can persist for months or years, epidemiologic studies have estimated case-fatality rates of ∼0.1%, principally from neurologic disease in older patients. There are no licensed vaccines or effective therapies to prevent or treat human CHIKV infections. We have developed a live CHIKV vaccine (CHIKV/IRES) that is highly attenuated yet immunogenic in mouse models, and is incapable of replicating in mosquito cells. In this study we sought to decipher the role of adaptive immunity elicited by CHIKV/IRES in protection against wild-type CHIKV infection. A single dose of vaccine effectively activated T cells with an expansion peak on day 10 post immunization and elicited memory CD4+ and CD8+ T cells that produced IFN-γ, TNF-α and IL-2 upon restimulation with CHIKV/IRES. Adoptive transfer of CHIKV/IRES-immune CD4+ or CD8+ T cells did not confer protection against wtCHIKV-LR challenge. By contrast, passive immunization with anti-CHIKV/IRES immune serum provided protection, and a correlate of a minimum protective neutralizing antibody titer was established. Overall, our findings demonstrate the immunogenic potential of the CHIKV/IRES vaccine and highlight the important role that neutralizing antibodies play in protection against an acute CHIKV infection.

•Enteroviruses increasingly noted as causing severe disease, especially in children.•Phase I clinical trial of inactivated B2 sub-genotype EV71 vaccine candidate.•Vaccine was safe, tolerable and induced 100% seroconversion after 2 doses in adults.•Measurable cross-neutralizing activity against heterologous sub-genotypes.•Results support further clinical development as a potential pediatric vaccine. Hand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide. In this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks. Of 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated. These data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children.

Armigeres subalbatus is a natural vector of the filarial worm Brugia pahangi, but it kills Brugia malayi microfilariae by melanotic encapsulation. Because B. malayi and B. pahangi are morphologically and biologically similar, comparing Ar. subalbatus-B. pahangi susceptibility and Ar. subalbatus-B. malayi refractoriness could provide significant insight into recognition mechanisms required to mount an effective anti-filarial worm immune response in the mosquito, as well as provide considerable detail into the molecular components involved in vector competence. Previously, we assessed the transcriptional response of Ar. subalbatus to B. malayi, and now we report transcriptome profiling studies of Ar. subalbatus in relation to filarial worm infection to provide information on the molecular components involved in B. pahangi susceptibility. Utilizing microarrays, comparisons were made between mosquitoes exposed to B. pahangi, B. malayi, and uninfected bloodmeals. The time course chosen facilitated an examination of key events in the development of the parasite, beginning with the very start of filarial worm infection and spanning to well after parasites had developed to the infective stage in the mosquito. At 1, 3, 6, 12, 24 h post infection and 2-3, 5-6, 8-9, and 13-14 days post challenge there were 31, 75, 113, 76, 54, 5, 3, 13, and 2 detectable transcripts, respectively, with significant differences in transcript abundance (increase or decrease) as a result of parasite development. Herein, we demonstrate that filarial worm susceptibility in a laboratory strain of the natural vector Ar. subalbatus involves many factors of both known and unknown function that most likely are associated with filarial worm penetration through the midgut, invasion into thoracic muscle cells, and maintenance of homeostasis in the hemolymph environment. The data show that there are distinct and separate transcriptional patterns associated with filarial worm susceptibility as compared to refractoriness, and that an infection response in Ar. subalbatus can differ significantly from that observed in Ae. aegypti, a common laboratory model.

Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/β and γ (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG). Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness). Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis) but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria parasite infections. These results could have an impact on vector infection and transmission dynamics in areas where Anopheles transmit both parasites, i.e., the elimination of filarial worms in a co-endemic locale could enhance malaria transmission.

•We investigated monovalent and tetravalent formulations of TDV in AG129 mice.•They were immunogenic and elicited neutralizing Ab and cellular responses.•Both formulations protected mice against a newly mouse adapted DENV-4 strain. Dengue (DEN) is the most important mosquito-borne viral disease, with a major impact on global health and economics, caused by four serologically and distinct viruses termed DENV-1 to DENV-4. Currently, there is no licensed vaccine to prevent DEN. We have developed a live attenuated tetravalent DENV vaccine candidate (TDV) (formally known as DENVax) that has shown promise in preclinical and clinical studies and elicits neutralizing antibody responses to all four DENVs. As these responses are lowest to DENV-4 we have used the AG129 mouse model to investigate the immunogenicity of monovalent TDV-4 or tetravalent TDV vaccines, and their efficacy against lethal DENV-4 challenge. Since the common backbone of TDV is based on an attenuated DENV-2 strain (TDV-2) we also tested the efficacy of TDV-2 against DENV-4 challenge. Single doses of the tetravalent or monovalent vaccines elicited neutralizing antibodies, anti-NS1 antibodies, and cellular responses to both envelope and nonstructural proteins. All vaccinated animals were protected against challenge at 60 days post-immunization, whereas all control animals died. Investigation of DENV-4 viremias post-challenge showed that only the control animals had high viremias on day 3 post-challenge, whereas vaccinated mice had no detectable viremia. Overall, these data highlight the excellent immunogenicity and efficacy profile of our candidate dengue vaccine in AG129 mice.

SCHOOL IS (STILL) IN SESSION During the two-day event, registrants had the opportunity to participate in two tracks of breakout sessions, featuring hot topics like price discovery and marketing, and how the agricultural industry helped Burger King change its mind on a controversial advertising campaign. COMMITTEES Given the unique circumstances of this year's convention, Texas & Southwestern Cattle Raisers Association's board of directors also took up a host of policy issues usually reserved for the association's Policy Conference. During the convention, the board of directors reviewed each committee's actions and voted to adopt them as final policy.

The policy supports the lawful use of drones over private land with property owner consent, and supports the use of drones for law enforcement purposes. The Property Rights and Tax Committee hosted Sen. Donna Campbell to discuss the municipal annexation reforms that she passed during the Texas Legislature's Special Session. Resolutions Unmanned Aerial Vehicles (LAW-7) WHEREAS, unmanned aerial vehicles (UAVs), also known as drones, are aircraft operated by a groundbased controller and possess the ability to transmit images and other information to the controller; and WHEREAS, UAVs have been proven to be useful in law enforcement and agricultural applications; and WHEREAS, private use of UAVs can cause concerns relating to trespass, privacy, and private property rights; now, therefore, be it RESOLVED, thatTSCRA supports the lawful use of UAVs controlled over private land by or with the approval of the owner and/or lessee ofthat private land; and, be it further RESOLVED, that TSCRA supports the use of UAVs for law enforcement purposes and that any controller of a UAV must comply with all applicable federal, state, and local laws and/or regulations, new 9/29/17 Agricultural Financing (MKT-22) WHEREAS, cattle producers regularly buy and sell cattle and feedstuffs which are financed; and WHEREAS, ensuring orderly financial transactions between buyer, seller, and lender of those products is crucial forthe continuance of the beef industry; and WHEREAS, agricultural liens secure payment or performance of a financial obligation on livestock, animal care orfeeding costs; and WHEREAS, agricultural lenders and borrowers rely on the statutory rights bestowed upon a secured party with a perfected lien; and WHEREAS, Texas is a Direct Notice state relative to security interests in farm products, as outlined in Section 1324 of the Food Security Act of 1985, whereby a lender who wants its security interestto survive the sale of a farm product is required to send notice of security interest in the farm products to buyers and potential buyers of the farm products; now, therefore, be it RESOLVED, thatTSCRA monitor and assess modifications to current financing practices and regulations and that any legislative or regulatory changes adhere to the following criteria: * Promote the implementation and use of sound business practices by buyers, sellers and lenders. * Require lenders and any other parties that extend credit to provide timely direct notice of a perfected lien to a purchaser. * Financial liability, compliance costs and lien notification burdens of lenders and their borrowers should not be transferred to other industry participants. * Liens should not be re-prioritized. * Direct notice and lien perfection standards should be equally administered, and specific production segments, borrowers or lenders should not receive preferential treatment over another. new 9/29/17 > Value-Added Marketing Programs (MKT-23) WHEREAS, cattle producers have long benefited from voluntarily participating in value-added cattle and beef programs that are certified or verified by USDA;and WHEREAS, value-added marketing programs have been developed by private industry in response to consumer demands and differentiate products to meetthose demands resulting in additional revenue to all supply chain participants; now, therefore, be it RESOLVED, thatTSCRA supports voluntary participation in value-added marketing programs; and, be it further RESOLVED, that TSCRA supports the acceptance of identification utilized in value-added marketing programs as official animal identification for animal disease traceability purposes so long as the identification meets animal disease traceability minimum standards, new 9/29/17 Business Expense Deductions (PRT-25) WHEREAS, the Internal Revenue Code allows taxpayers to deductfrom their gross income ordinary and necessary expenses paid or incurred in carrying on a trade or business; and WHEREAS, the Internal Revenue Code allows taxpayers to deductthe full purchase price of qualified business equipment in the same year it was purchased instead of deducting depreciation over multiple years; and WHEREAS, cattle raisers and ranchers frequently own and operate their own business; and WHEREAS, business expense deductions are essential to allow continued investment in those businesses; now, therefore, be it RESOLVED, thatTSCRA supports the continuation of business expense deductions through the Internal Revenue Code, new 9/29/17

We examine the relationship between electric vehicle battery chemistry and supply chain disruption vulnerability for four critical minerals: lithium, cobalt, nickel, and manganese. We compare the nickel manganese cobalt (NMC) and lithium iron phosphate (LFP) cathode chemistries by (1) mapping the supply chains for these four materials, (2) calculating a vulnerability index for each cathode chemistry for various focal countries and (3) using network flow optimization to bound uncertainties. World supply is currently vulnerable to disruptions in China for both chemistries: 80% [71% to 100%] of NMC cathodes and 92% [90% to 93%] of LFP cathodes include minerals that pass through China. NMC has additional risks due to concentrations of nickel, cobalt, and manganese in other countries. The combined vulnerability of multiple supply chain stages is substantially larger than at individual steps alone. Our results suggest that reducing risk requires addressing vulnerabilities across the entire battery supply chain. Electric vehicle battery supply chains are currently vulnerable to supply disruptions in China, but research shows that the cumulative effect of multiple supply chain steps creates additional vulnerabilities across multiple critical battery minerals.