Development and Characterization of a Live-attenuated Vaccine to Combat Equine Herpesvirus Type-1 infections

Equine Herpesvirus 1 (EHV-1) is an important ubiquitous enzootic equine pathogen and one of the most common pathogens of the horse, causing, respiratory disease, epidemic abortion, occasionally neurological disease in horses, which leads to significant economic losses to the horse industry. EHV-1 induces several clinical signs of disease ranging in severity, from mild respiratory disease to abortion in pregnant mares, neonatal foal death and neuropathogenic disorders. Natural EHV-1 infection stimulated short lived protective immunity and had both humoral and cellular immune responses. Currently vaccination remains the best option to prevent EHV-1 infection and different applications of vaccination have been investigated and developed over the past decades. The objective of this research was the design of a safe and effective virus-vectored vaccine to prevent EHV-1 infections. In this research, EHV-1 glycoprotein D (gD) gene was cloned into the Herpes Simplex Virus Type-1 (HSV-1) VC2 vector, which contains the gK∆31-68 deletion and UL20∆2-22 deletion. The VC2 strain cannot infect axonal neurons of mice and rats and has been shown to produce protective immune responses against both HSV-1 and HSV-2 viruses in mice and guinea pigs. Vaccination of mice with the HSV-VC2-EHV-gD increased virus neutralizing activities against EHV-1 (33.6%) in mice after three vaccinations, which was similar to commercial whole virus vaccine group (32.6%) and significantly higher than VC2 and Unvaccinated control groups (p\u3c0.01 or p\u3c0.001). Mice vaccinated with the VC2-EHV-gD group exhibited significantly higher humoral and cellular immune responses as detected by polychromatic flow cytometry when compared to the other groups (p\u3c0.01 or p\u3c0.001). Induction of IgG1 and IgG2a antibodies were significantly higher in the VC2-EHV-gD group than other groups after three vaccinations (p\u3c0.001). It’s interesting that induction of IgM antibody in the Vetera group was significantly higher than other groups before and after challenge (p\u3c0.01 or P\u3c0.05). Vaccination with the VC2-EHV-gD also stimulated strong cellular immune response (IFN-γ and TNF). Additional studies are needed to assess the VC2-EHV-gD vaccine efficacy in generating protective humoral and cellular immune responses in horses

Immunization of West Nile recombinant envelope Domain III with equine CD40 ligand protein vaccine induced specific immune response in rabbits and horses

West Nile virus (WNV) is one of several flaviruses known to infect mammalian species, including humans. There were 15,257 horse cases reported in 2002 and 1,086 in 2006 in United States. Recently, significant increases in equine and human cases have been reported in United States. Domain III of the WNV envelope protein binds to cellular receptors, and induces a significant portion of the neutralizing antibody response against the virus. CD40 Ligand (CD40L, CD154) enhances productive interactions between T cells and APC and has been shown to function as a potential adjuvant. In this study, we constructed and expressed a fusion protein consisting of the Domain III of WNV envelope protein fused in-frame with the soluble portion of the equine CD40L. Immunizations of rabbits revealed that the recombinant protein induced antibody that specifically reacted with the WNV and neutralized the virus. Similar experiments were performed with horses. Western immunoblots confirmed that vaccinated horses produced antibodies that specifically reacted with the recombinant WNV E DIII proteins. The recombinant DIII protein with TiterMax or CD40L or both as adjuvant(s) induced significantly higher anti-WNV E DIII antibody activities than control and DIII alone groups after first vaccination. The recombinant DIII-CD40L protein vaccine continually induced the anti-WNV E DIII antibody activities without the adjuvant TiterMax. Moreover, the groups immunized with DIII-CD40L+TiterMax and DIII-CD40L showed stronger neutralization activities from week 8 than the other groups, and they maintained the high titers for at least 10 weeks. The results showed that healthy horses vaccinated with recombinant WNV E DIII protein with equine CD40L demonstrated an antigen specific humoral immune response. The responses were enhanced by booster vaccination. Vaccination with this recombinant WNV E DIII-CD40L protein induced a WNV specific immunity in healthy horses that might contribute to protection from WNV-associated disease. CD40L could be utilized as a non-toxic, alternative adjuvant to boost the immunogenicity of subunit vaccines in horses

Cross-relation Cross-bag Attention for Distantly-supervised Relation Extraction

Distant supervision leverages knowledge bases to automatically label instances, thus allowing us to train relation extractor without human annotations. However, the generated training data typically contain massive noise, and may result in poor performances with the vanilla supervised learning. In this paper, we propose to conduct multi-instance learning with a novel Cross-relation Cross-bag Selective Attention (C$^2$SA), which leads to noise-robust training for distant supervised relation extractor. Specifically, we employ the sentence-level selective attention to reduce the effect of noisy or mismatched sentences, while the correlation among relations were captured to improve the quality of attention weights. Moreover, instead of treating all entity-pairs equally, we try to pay more attention to entity-pairs with a higher quality. Similarly, we adopt the selective attention mechanism to achieve this goal. Experiments with two types of relation extractor demonstrate the superiority of the proposed approach over the state-of-the-art, while further ablation studies verify our intuitions and demonstrate the effectiveness of our proposed two techniques.Comment: AAAI 201

Surgical treatment of spinal tenosynovial giant cell tumor: Experience from a single center and literature review

IntroductionSpinal tenosynovial giant cell tumor (TGCT) is a rare benign primary spinal tumor with aggressive behavior. The treatment strategy and prognosis of spinal TGCT remain unclear. This retrospective study aimed to evaluate the effectiveness of surgical treatment of spinal TGCT.MethodsWe enrolled 18 patients with spinal TGCT who underwent surgical treatment in our hospital between January 2002 and January 2021. Additionally, we reviewed 72 cases of spinal TGCT with surgical treatment reported in the previous literature. Therefore, a total of 90 cases of spinal TGCT were evaluated for their clinical characteristics, surgical details, radiotherapy, and prognosis.ResultsIn terms of the extent of resection, 73 cases (81.1%) underwent gross total resection (GTR), and 17 cases (18.9%) underwent subtotal resection (STR). Regarding the technique of GTR, 12 cases (16.7%) underwent en bloc resection, while 60 cases (83.3%) underwent piecemeal resection. During a median follow-up duration of 36 months (range: 3–528 months), 17.8% (16/90) cases experienced local recurrence/progression. The local recurrence/progression rate in cases that underwent GTR was 8.2% (6/73), which was significantly lower than that in cases with STR (58.8%, 10/17) (p<0.001). The local recurrence/progression rate of en bloc resection was 8.3% (1/12), and that of piecemeal resection was 8.3% (5/60). Twelve cases underwent perioperative adjuvant radiotherapy, and one (8.3%, 1/12) of them showed disease progression during follow-up. Six recurrent/progressive lesions were given radiotherapy and all of them remained stable in the subsequent follow-up. Eight recurrent/progressive lesions were only treated with re-operation without radiotherapy, and half of them (50.0%, 4/8) demonstrated repeated recurrence/progression in the subsequent follow-up.ConclusionSurgical treatment could be effective for spinal TGCT cases, and GTR is the preferred surgical strategy. Piecemeal resection may be appropriate for spinal TGCT cases with an acceptable local recurrence/progression rate. Perioperative adjuvant radiotherapy may reduce the risk of postoperative local recurrence/progression, and radiotherapy plays an important role in the treatment of recurrent/unresectable spinal TGCT lesions