Isaacs A, Cheung S T M, Thakur N, Jaberolansar N, Young A, Modhiran N, Bailey D, Graham S P, Young P R, Chappell K J, Watterson D (2021)

Combinatorial F-G immunogens as Nipah and respiratory syncytial virus vaccine candidates

Viruses 13 (10), 1942
Publisher’s version: https://doi.org/10.3390/v13101942

Abstract

Nipah virus (NiV) and respiratory syncytial virus (RSV) possess two surface glycoproteins involved in cellular attachment and membrane fusion, both of which are potential targets for vaccines. The majority of vaccine development is focused on the attachment (G) protein of NiV, which is the immunodominant target. In contrast, the fusion (F) protein of RSV is the main target in vaccine development. Despite this, neutralising epitopes have been described in NiV F and RSV G, making them alternate targets for vaccine design. Through rational design, we have developed a vaccine strategy applicable to phylogenetically divergent NiV and RSV that comprises both the F and G proteins (FxG). In a mouse immunization model, we found that NiV FxG elicited an improved immune response capable of neutralising pseudotyped NiV and a NiV mutant that is able to escape neutralisation by two known F-specific antibodies. RSV FxG elicited an immune response against both F and G and was able to neutralise RSV; however, this was inferior to the immune response of F alone. Despite this, RSV FxG elicited a response against a known protective epitope within G that is conserved across RSV A and B subgroups, which may provide additional protection in vivo. We conclude that inclusion of F and G antigens within a single design provides a streamlined subunit vaccine strategy against both emerging and established pathogens, with the potential for broader protection against NiV.

Abstract

Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals with serious economic consequences. FMD is endemic in Southeast Asia (SEA) and East Asia (EA) with the circulation of multiple serotypes, posing a threat to Australia and other FMD-free countries. Although vaccination is one of the most important control measures to prevent FMD outbreaks, the available vaccines may not be able to provide enough cross-protection against the FMD viruses (FMDVs) circulating in these countries due to the incursion of new lineages and sub-lineages as experienced in South Korea during 2010, a FMD-free country, when a new lineage of serotype O FMDV (Mya-98) spread to the country, resulting in devastating economic consequences. In this study, a total of 62 serotype O (2013–2018) viruses selected from SEA and EA countries were antigenically characterized by virus neutralization tests using three existing (O/HKN/6/83, O/IND/R2/75 and O/PanAsia-2) and one putative (O/MYA/2009) vaccine strains and full capsid sequencing. The Capsid sequence analysis revealed three topotypes, Cathay, SEA and Middle East-South Asia (ME-SA) of FMDVs circulating in the region. The vaccines used in this study showed a good match with the SEA and ME-SA viruses. However, none of the recently circulating Cathay topotype viruses were protected by any of the vaccine strains, including the existing Cathay topotype vaccine (O/HKN/6/83), indicating an antigenic drift and, also the urgency to monitor this topotype in the region and develop a new vaccine strain if necessary, although currently the presence of this topotype is mainly restricted to China, Hong Kong, Taiwan and Vietnam. Further, the capsid sequences of these viruses were analyzed that identified several capsid amino acid substitutions involving neutralizing antigenic sites 1, 2 and 5, which either individually or together could underpin the observed antigenic drift.

Abstract

Diverse strains of Wolbachia bacteria, carried by many arthropods, as well as some nematodes, interact in many different ways with their hosts. These include male killing, reproductive incompatibility, nutritional supplementation and suppression or enhancement of the transmission of diseases such as dengue and malaria. Consequently, Wolbachia have an important role to play in novel strategies to control human and livestock diseases and their vectors. Similarly, cell lines derived from insect hosts of Wolbachia constitute valuable research tools in this field. During the generation of novel cell lines from mosquito and sand fly vectors, we isolated two strains of Wolbachia and demonstrated their infectivity for cells from a range of other insects and ticks. These new insect cell lines and Wolbachia strains will aid in the fight against mosquitoes, sand flies and, potentially, ticks and the diseases that these arthropods transmit to humans and their domestic animals.

Abstract

Host-microbiota interactions are important in shaping immune responses that have the potential to influence the outcome of pathogen infection. However, most studies have focused on the gut microbiota and its possible association with disease outcome, while the role of the nasal microbiota and respiratory pathogen infection has been less well studied. Here we examined changes in the composition of the nasal microbiota of pigs following experimental infection with porcine reproductive and respiratory syndrome virus 2 (PRRSV-2), swine influenza A H3N2 virus (H3N2) or both viruses. DNA extracted from nasal swabs were subjected to 16S rRNA sequencing to study the composition of the nasal microbiota. Bacterial richness fluctuated in all groups, with a slight reduction in pigs singly infected with PRRSV-2 and H3N2 during the first 5 days of infection compared to uninfected controls. In contrast, nasal bacterial richness remained relatively stable after PRRSV-2/H3N2 co-infection. PRRSV-2 and H3N2, alone or in combination differentially altered the abundance and distribution of bacterial families. Single and co-infection with PRRSV-2 or H3N2 was associated with the expansion of the Neisseriaceae family. A positive correlation between H3N2 viral load and the relative abundance of the Neisseriaceae was observed. However, further mechanistic studies are required to understand the significance of the changes in specific bacterial families following these viral infections.

Abstract

Tanzania has the second largest livestock population in Africa and livestock keeping is an integral part of most people’s livelihoods. Foot-and-mouth disease (FMD) is a transboundary disease, affecting cloven-hoofed animals, that is currently endemic in Tanzania. The Tanzania Development Vision 2025 aspires to make the livestock sector more competitive. Part of this plan foresees establishing a FMD disease free zone in Rukwa region to be able to increase the export of animals and animal products. The aim of this study was to assess the economic efficiency and feasibility of establishing such an FMD-free zone and to advise policy makers on the profitability of the investment. A stochastic benefit-cost model, set-up in Palisade @Risk for Excel for a time frame of ten years, was developed to assess whether the benefits of establishing a FMD-free zone would outweigh the costs. Data were collated from reviewing literature, government statistics, and key informant interviews with farmers, traders and veterinarians in Tanzania, and complemented by informed assumptions and expert opinion. Moreover, feasibility aspects including underlying infrastructure, market structures and resource availability were discussed based on key informant interviews, literature review and historical analyses. The net present value for the establishment of a FMD-free zone was negative and the benefit-cost ratio was below one (mean 0.09, min 0.05 - max 0.15 in the scenario considering vaccination of all susceptible domestic animals, and mean 0.11; min 0.06 - max 0.20 when considering vaccinating cattle only), excluding potential benefits from trade. The sensitivity analysis showed that variables related to the cost of vaccination had the largest negative impact on the net present value. The proposed FMD-free zone in Rukwa region is unlikely to be cost-effective with the current FMD status and export trade prospects in Tanzania. Interviews with stakeholders revealed that vaccine availability, funding, farmers’ willingness to participate and lack of staff continuity in key roles were the main barriers to establish a reliable FMD control programme in the country. Recommendations towards FMD control and potential short and middle term strategies are discussed.

Abstract

Food systems are increasingly under threat, with climate, biological, economic or policy shocks and stressors occurring at an increasing frequency and scale. Their complex and fragile nature has become even more apparent during the COVID-19 pandemic. A systematic review of news articles published globally between December 2019 and April 2020 was conducted to describe the impacts of the COVID-19 pandemic on the chicken meat system and to identify key vulnerabilities and intervention points to build resilience. Most of the impacts identified were caused by a combination of the different mitigation measures implemented by the system actors such as movement restrictions rather than by the direct effects of the virus, thereby demonstrating the importance of interconnections and coordination in the system. Social media were found to have played a crucial role in amplifying, mitigating or mediating the impact of the pandemic. The findings highlight the importance of adopting a holistic approach that integrates the multiple dimensions of food systems for effective responses to systemic shocks.

Ramakrishnan E P, Gupta S, Gadhari R, Bharti N, Malviya S, Kasibhatla S M, Kim J, Joshi R (2021)

GAMUT: A genomics big data management tool

Journal of Biosciences 46 (4), 89

Abstract

Efficient analysis of Single Nucleotide Polymorphisms (SNPs) across genomic samples enable in deciphering the relationship between genotype and phenotype. The core principle behind SNP comparison is to arrive at a probable list of variants that can differentiate two sets of data (populations). Such SNPs have direct applications in array design, genotype imputation and in cataloging of variants in regions of interest. We have developed GAMUT (Genomics bigdAta Management Tool), a big data-based solution for efficient run-time comparison of SNPs across large datasets based on partition of samples belonging to different populations taking into account user-defined splits. The tool is based on client-server architecture with MongoDB at the back-end and JSF with PrimeFaces as the front-end. It is readily deployable on wild-fly server as well as a docker container. Spark-based parallel data uploader enables optimal loading times. GAMUT enables dynamic querying of the large datasets consisting of multiple samples using text-based, chromosome position-based as well as gene-name based options. Various charting options like bar and pie charts along with tabular formats are available to ease the analysis of the queried data. The resultant data pertaining to comparison of genome-wide SNPs can also be downloaded in different formats like text, html, json for further stand-alone analysis. GAMUT is available for download at: https://github.com/bioinformatics-cdac/gamut

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