Long Term Protective Immunity to Goatpox in Goats After Single Immunization with a Live Attenuated Goatpox Vaccine

In this study, duration of immunity following single shot vaccination using an attenuated goatpox vaccine (GTPV/Uttarkashi/1978) was evaluated in sero-negative kids for 52 months. Long term immunity was evaluated by clinical protection upon virulent virus challenge and serum neutralization assay applied for serum samples. Rise in level of GTPV specific antibodies was found to be maximum on 21 days post vaccination, which was maintained between 1 and 2 years of immunization with steady decline. Upon virulent virus challenge on 21 days, 12, 24, 42 and 52 months post vaccination, protection in all vaccinated animals was evident, whereas, control animals developed severe clinical disease. This is for the first time that long term immunity of a live goatpox vaccine has been investigated up to 52 months of post-vaccination in goats and it has immense potential in controlling and eradicating goatpox from an enzootic situation.

Time-Series prediction for the epidemic trends of COVID-19 using Conditional Generative adversarial Networks Regression on country-wise case studies

Probabilistic Regression is a statistical technique and a crucial problem in the machine learning domain which employs a set of machine learning methods to forecast a continuous target variable based on the value of one or multiple predictor variables. COVID-19 is a virulent virus that has brought the whole world to a standstill. The potential of the virus to cause inter human transmission makes the world a dangerous place. This thesis predicts the upcoming circumstances of the Corona virus to subside its action. We have performed Conditional GAN regression to anticipate the subsequent Covid-19 cases of 5 countries. The GAN variant CGAN is used to design the model and predict the Covid-19 cases for three months ahead with least error for the dataset provided. Each country is examined individually, due to their variation in population size, tradition, medical manage- ment, preventive measures. The analysis is based on confirmed data, as provided by the World Health Organization. This paper investigates how conditional Generative Adversarial Networks (GANs) can be used to accurately exhibit intricate conditional distributions. GANs have got spectacular achievement in producing convoluted highdimensional data, but work done on their use for regression prob- lems is minimal. This paper exhibits how conditional GANs can be employed in probabilistic regression. It is shown that conditional GANs can be used to evaluate a wide range of various distributions and be competitive with existing probabilistic regression models.

Pathotyping of Newcastle Disease Virus: a Novel Single BsaHI Digestion Method of Detection and Differentiation of Avirulent Strains (Lentogenic and Mesogenic Vaccine Strains) from Virulent Virus

The extensive use of the NDV vaccine strain and the existence of avirulent NDV strains in wild birds makes it difficult to diagnose Newcastle Disease virus (NDV). The intracerebral pathogenicity index (ICPI) and/or sequencing-based identification, which are required to determine virulent NDV, are time-consuming, costly, difficult, and cruel techniques.

Exchange of C-Terminal Variable Sequences within Morbillivirus Nucleocapsid Protein Are Tolerated: Development and Evaluation of Two Marker (DIVA) Vaccines (Sungri/96 DIVA, Nigeria/75/1 DIVA) against PPR

Across Africa, the Middle East, and Asia, peste des petits ruminants virus (PPRV) places a huge disease burden on agriculture, affecting, in particular, small ruminant production. The recent PPR outbreaks in Northern Africa, the European part of Turkey, and Bulgaria represent a significant threat to mainland Europe, as a source of disease. Although two safe and efficacious live attenuated vaccines (Sungri/96 and Nigeria/75/1) are available for the control of PPR, current serological tests do not enable the differentiation between naturally infected and vaccinated animals (DIVA). The vaccinated animals develop a full range of immune responses to viral proteins and, therefore, cannot be distinguished serologically from those that have recovered from a natural infection. This poses a serious problem for the post-vaccinal sero-surveillance during the ongoing PPR eradication program. Furthermore, during the latter stages of any eradication program, vaccination is only possible if the vaccine used is fully DIVA compliant. Using reverse genetics, we have developed two live attenuated PPR DIVA vaccines (Sungri/96 DIVA and Nigeria/75/1 DIVA), in which the C-terminal variable region of the PPRV N-protein has been replaced with dolphin morbillivirus (DMV). As a proof of principle, both the DIVA vaccines were evaluated in goats in pilot studies for safety and efficacy, and all the animals were clinically protected against the intranasal virulent virus challenge, similar to the parent vaccines. Furthermore, it is possible to differentiate between infected animals and vaccinated animals using two newly developed ELISAs. Therefore, these DIVA vaccines and associated tests can facilitate the sero-monitoring process and speed up the implementation of global PPR eradication through vaccination.

Development of the Inactivated QazCovid-in Vaccine: Protective Efficacy of the Vaccine in Syrian Hamsters

In March 2020, the first cases of the human coronavirus disease COVID-19 were registered in Kazakhstan. We isolated the SARS-CoV-2 virus from clinical materials from some of these patients. Subsequently, a whole virion inactivated candidate vaccine, QazCovid-in, was developed based on this virus. To develop the vaccine, a virus grown in Vero cell culture was used, which was inactivated with formaldehyde, purified, concentrated, sterilized by filtration, and then adsorbed on aluminum hydroxide gel particles. The formula virus and adjuvant in buffer saline solution were used as the vaccine. The safety and protective effectiveness of the developed vaccine were studied in Syrian hamsters. The results of the studies showed the absolute safety of the candidate vaccine in the Syrian hamsters. When studying the protective effectiveness, the developed vaccine with an immunizing dose of 5 μg/dose specific antigen protected animals from a wild homologous virus at a dose of 104.5 TCID50/mL. The candidate vaccine induced the formation of virus-neutralizing antibodies in vaccinated hamsters at titers of 3.3 ± 1.45 log2 to 7.25 ± 0.78 log2, and these antibodies were retained for 6 months (observation period) for the indicated titers. No viral replication was detected in vaccinated hamsters, protected against the development of acute pneumonia, and ensured 100% survival of the animals. Further, no replicative virus was isolated from the lungs of vaccinated animals. However, a virulent virus was isolated from the lungs of unvaccinated animals at relatively high titers, reaching 4.5 ± 0.7 log TCID50/mL. After challenge infection, 100% of unvaccinated hamsters showed clinical symptoms (stress state, passivity, tousled coat, decreased body temperature, and body weight, and the development of acute pneumonia), with 25 ± 5% dying. These findings pave the way for testing the candidate vaccine in clinical human trials.

Confirmation of Oryctes rhinoceros nudivirus infections in G-haplotype coconut rhinoceros beetles (Oryctes rhinoceros) from Palauan PCR-positive populations

Coconut rhinoceros beetle (CRB), Oryctes rhinoceros, is a pest of palm trees in the Pacific. Recently, a remarkable degree of palm damage reported in Guam, Hawaii, Papua New Guinea and Solomon Islands has been associated with a particular haplotype (clade I), known as “CRB-G”. In the Palau Archipelago, both CRB-G and another haplotype (clade IV) belonging to the CRB-S cluster coexist in the field. In this study, more than 75% of pheromone trap-captured adults of both haplotypes were Oryctes rhinoceros nudivirus (OrNV)-positive by PCR. No significant difference in OrNV prevalence between the haplotypes was detected. In PCR-positive CRB-G tissue specimens from Palau, viral particles were observed by electron microscopy. Hemocoel injection of CRB larvae with crude virus homogenates from these tissues resulted in viral infection and mortality. OrNV isolated from Palauan-sourced CRB was designated as OrNV-Palau1. Both OrNV-Palau1 and OrNV-X2B, a CRB biological control isolate released in the Pacific, were propagated using the FRI-AnCu-35 cell line for production of inoculum. However, the OrNV-Palau1 isolate exhibited lower viral production levels and longer larval survival times compared to OrNV-X2B in O. rhinoceros larvae. Full genome sequences of the OrNV-Palau1 and -X2B isolates were determined and found to be closely related to each other. Altogether these results suggest CRB adults in Palau are infected with a less virulent virus, which may affect the nature and extent of OrNV-induced pathology in Palauan populations of CRB.

Computer-Aided Identification of Bioactive compounds of Azadirachta indica (Neem) with Potential activity against SARS-CoV-2 main protease

Coronavirus disease 2019 (COVID-19) is a zoonotic disease caused by a novel virulent virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Up till now, there is still a continuous increase in cases, morbidity and fatality associated with the disease throughout the world. Azadirachta indica (Neem) is a medicinal plant popularly known for its antimalarial and broad-spectrum antiviral activities. The bioactive compounds of Neem were therefore analyzed in this study for possible inhibitory activity against the SARS-CoV-2 3-Chymotrypsin (3C)-like protease (Main protease), an important therapeutic target of the virus. This was done through a computational approach involving molecular docking, pharmacophore modelling and ADMET studies. Out of 150 Neem compounds subjected to molecular docking against the main protease, rutin had the highest binding affinity followed by tannin amine, quercitrin, hyperoside and kaempferol, before the standard inhibitor K36. The compounds interacted with Glu-166, Asn-142, His- 41, Cys-145 and other crucial amino acids residues of the catalytic cleft of the protease. Most of the selected compounds displayed acceptable drug-likeness, pharmacokinetic and toxicity parameters. These compounds could therefore be developed further for the treatment and management of COVID-19 after experimental studies.

Pathotyping of Newcastle disease virus: A novel single BsaHI digestion method of detection and differentiation of avirulent strains (lentogenic and mesogenic vaccine strains) from virulent virus

We provide a novel single restriction enzyme (RE) (BsaHI) digestion approach for detecting distinct pathotypes of the Newcastle disease virus (NDV). After scanning 4000 F gene nucleotide sequences in the NCBI database, a single RE (BsaHI) digesting site was discovered in the cleavage site. APMV-I "F gene" Class II specific primer-based reverse transcriptase PCR (RT-PCR) was utilized to amplify a 535 bp fragment, which was then digested with a single RE (BsaHI) for pathotyping avian NDV field isolates and pigeon paramyxovirus-1 isolates. The avirulent (lentogenic and mesogenic strains) produce 189 and 346 bp fragments, respectively, but the result in velogenic strains remains undigested with 535 bp fragments. In addition, 45 field NDV isolates and 8 vaccine strains were used to confirm the approach. The sequence-based analysis also agrees with the data obtained utilizing the single RE (BsaHI) digestion approach. The proposed technique had the potential to distinguish between avirulent and virulent strains in a short space of time, making it valuable in NDV surveillance and monitoring research.

Predictability of COVID-19-related morbidity and mortality based on model estimations to establish proactive protocols of countermeasures

The COVID-19 pandemic (SARS-CoV-2) has revealed the need for proactive protocols to react and act, imposing preventive and restrictive countermeasures on time in any society. The extent to which confirmed cases can predict the morbidity and mortality in a society remains an unresolved issue. The research objective is therefore to test a generic model’s predictability through time, based on percentage of confirmed cases on hospitalized patients, ICU patients and deceased. This study reports the explanatory and predictive ability of COVID-19-related healthcare data, such as whether there is a spread of a contagious and virulent virus in a society, and if so, whether the morbidity and mortality can be estimated in advance in the population. The model estimations stress the implementation of a pandemic strategy containing a proactive protocol entailing what, when, where, who and how countermeasures should be in place when a virulent virus (e.g. SARS-CoV-1, SARS-CoV-2 and MERS) or pandemic strikes next time. Several lessons for the future can be learnt from the reported model estimations. One lesson is that COVID-19-related morbidity and mortality in a population is indeed predictable. Another lesson is to have a proactive protocol of countermeasures in place.

Development Of The Inactivated QazCovid-In Vaccine: Protective Efficacy Of The Vaccine In Syrian Hamsters

In March 2020, the first cases of human coronavirus infection COVID-19 were registered in Kazakhstan. We isolated the SARS-CoV-2 virus from the clinical material from the patients. Subsequently, a whole virion inactivated candidate vaccine, QazCovid-in, was developed based on this virus. To obtain the vaccine, a virus grown in Vero cell culture was used, which was inactivated with formaldehyde, purified, concentrated, sterilized by filtration, and then sorbed on aluminum hydroxide gel particles. The formula virus and adjuvant in buffer saline solution was used as a vaccine. The safety and protective effectiveness of the developed vaccine was studied on Syrian hamsters. The results of the studies showed the absolute safety of the candidate vaccine on the Syrian hamsters. When studying the protective effectiveness, the developed vaccine with an immunizing dose of 5 mcg/dose of a specific antigen protected animals from wild virus at a dose of 104.5 TCID50/ml. The candidate vaccine formed virus-neutralizing antibodies in vaccinated hamsters in titers from 3.3 ± 1.45 log2 to 7.25 ± 0.78 log2, which were retained for 6 months (observation period) in the indicated titers. The candidate vaccine suppressed the replication of the wild virus in the body of vaccinated hamsters, protected against the development of acute pneumonia and ensured 100% survival of the animals. At the same time, no replicative virus was isolated from the lungs of vaccinated animals. At the same time, a virulent virus was isolated from the lungs of unvaccinated animals in relatively high titers, reaching 4.5 ± 0.7 lg TCID50/ml. After challenge infection, 100% of unvaccinated hamsters became ill with clinical signs (stress state, passivity, tousled coat, decreased body temperature and body weight, and the development of acute pneumonia), of which 25 ± 5% were fatal. The findings paved the way for testing the candidate vaccine in humans in clinical trials.