An attenuated herpesvirus vectored vaccine candidate induces T-cell responses against highly conserved porcine reproductive and respiratory syndrome virus M and NSP5 proteins that are unable to control infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a leading cause of economic loss in pig farming worldwide. Existing commercial vaccines, all based on modified live or inactivated PRRSV, fail to provide effective immunity against the highly diverse circulating strains of both PRRSV-1 and PRRSV-2. Therefore, there is an urgent need to develop more effective and broadly active PRRSV vaccines. In the absence of neutralizing antibodies, T cells are thought to play a central role in controlling PRRSV infection. Herpesvirus-based vectors are novel vaccine platforms capable of inducing high levels of T cells against encoded heterologous antigens. Therefore, the aim of this study was to assess the immunogenicity and efficacy of an attenuated herpesvirus-based vector (bovine herpesvirus-4; BoHV-4) expressing a fusion protein comprising two well-characterized PRRSV-1 T-cell antigens (M and NSP5). Prime-boost immunization of pigs with BoHV-4 expressing the M and NSP5 fusion protein (vector designated BoHV-4-M-NSP5) induced strong IFN-γ responses, as assessed by ELISpot assays of peripheral blood mononuclear cells (PBMC) stimulated with a pool of peptides representing PRRSV-1 M and NSP5. The responses were closely mirrored by spontaneous IFN-γ release from unstimulated cells, albeit at lower levels. A lower frequency of M and NSP5 specific IFN-γ responding cells was induced following a single dose of BoHV-4-M-NSP5 vector. Restimulation using M and NSP5 peptides from PRRSV-2 demonstrated a high level of cross-reactivity. Vaccination with BoHV-4-M-NSP5 did not affect viral loads in either the blood or lungs following challenge with the two heterologous PRRSV-1 strains. However, the BoHV-4-M-NSP5 prime-boost vaccination showed a marked trend toward reduced lung pathology following PRRSV-1 challenge. The limited effect of T cells on PRRSV-1 viral load was further examined by analyzing local and circulating T-cell responses using intracellular cytokine staining and proliferation assays. The results from this study suggest that vaccine-primed T-cell responses may have helped in the control of PRRSV-1 associated tissue damage, but had a minimal, if any, effect on controlling PRRSV-1 viral loads. Together, these results indicate that future efforts to develop effective PRRSV vaccines should focus on achieving a balanced T-cell and antibody response.

An investigation of the cognitive and neural correlates of semantic memory search related to creative ability.

Creative ideas likely result from searching and combining semantic memory knowledge, yet the mechanisms acting on memory to yield creative ideas remain unclear. Here, we identified the neurocognitive correlates of semantic search components related to creative abilities. We designed an associative fluency task based on polysemous words and distinguished two search components related to clustering and switching between the different meanings of the polysemous words. Clustering correlated with divergent thinking, while switching correlated with the ability to combine remote associates. Furthermore, switching correlated with semantic memory structure and executive abilities, and was predicted by connectivity between the default, control, and salience neural networks. In contrast, clustering relied on interactions between control, salience, and attentional neural networks. Our results suggest that switching captures interactions between memory structure and control processes guiding the search whereas clustering may capture attentional controlled processes for persistent search, and that alternations between exploratory search and focused attention support creativity.

Necropsy Procedures and Evaluation of Macroscopic Lesions of Pigs Infected with African Swine Fever Virus.

Pathology complements and provides a fundamental link to other disciplines for disease investigations supporting molecular biology, genetics, immunology, or virology as core basis of scientific research. Necropsies are an essential tool in veterinary pathology for disease investigation and should be conducted in a routine, systematic, and standard approach. An orderly necropsy procedure will allow the prosector (veterinary clinicians or veterinary pathologists) to determine macroscopically normal or altered structures and allow, through experience, to acquire dexterity, speed, and confidence in the technique. In conjunction with standardized macroscopic scoring protocols, necropsy is a powerful tool especially when using experimental animal models in research. Here, we describe a systematic necropsy protocol to be conducted on pigs infected with African swine fever virus (ASFV). The methodology described only requires rudimentary instruments, and it is not time-consuming. In addition to performing accurate tissue and organ assessment, the technique intends the prosector to carry out sampling of organs and tissues of interest in ASFV-infected pigs.

Brain connectivity-based prediction of real-life creativity is mediated by semantic memory structure.

Associative theories of creativity argue that creative cognition involves the abilities to generate remote associations and make useful connections between unrelated concepts in one's semantic memory. Yet, whether and how real-life creative behavior relies on semantic memory structure and its neural substrates remains unclear. We acquired multi-echo functional magnetic resonance imaging data while participants underwent a semantic relatedness judgment task. These ratings were used to estimate their individual semantic memory networks, whose properties significantly predicted their real-life creativity. Using a connectome predictive modeling approach, we identified patterns of task-based functional connectivity that predicted creativity-related semantic memory network properties. Furthermore, these properties mediated the relationship between functional connectivity and real-life creativity. These results provide new insights into how brain connectivity patterns support real-life creative behavior via the structure of semantic memory. We also show how computational network science can be used to couple behavioral, cognitive, and neural levels of analysis.

Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms.

mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.

PtCl2-catalyzed cycloisomerizations of 5-en-1-yn-3-ol systems.

5-En-1-yn-3-ol substrates bearing a free hydroxyl group or an acyl group are highly versatile partners for PtCl2-catalyzed cycloisomerizations. Electrophilic activation of the alkyne moiety triggers at wish a hydride or an O-acyl migration yielding at the end to regioisomeric keto derivatives. The efficient preparation of Sabina ketone, an important monoterpene precursor, has been worked out.