Veterinary Vaccine最新文献

Gastrointestinal nematodes (GINs) infect sheep, goats and cattle, causing huge economic losses to the breeding industry worldwide. The current major control method is the usage of anthelmintic drugs, however, the widespread issue of parasite anthelmintic resistance means that this approach is becoming unsustainable. Vaccination has been regarded as a long-term and sustainable intervention strategy for controlling these parasitoses. In the past several decades, substantial progress has been made in developing vaccines against GINs infection in grazing ruminants. Many natural proteins of GINs have been identified as effective candidate antigens, which could induce a high level of protective immunity against these GINs infection in ruminants, but the recombinant forms of these native antigens have not achieved satisfactory immunoprotective effects. This review summarizes the progress and challenges for developing vaccines against the main GINs, including Haemonchus contortus, Ostertagia ostertagi, Teladorsagia circumcincta, Cooperia oncophora and Trichostrongylus colubriformi, as well as provides a perspective on promoting the progress of commercially viable recombinant subunit vaccines.

Porcine circovirus type 2 (PCV2) is a globally important pathogen of swine with a high capacity for genetic change, potentially including evolution of strains less susceptible to vaccine induced immunity. Starting with DNA sequences, in silico tools can be used to predict the T cell epitope content of the PCV2 capsid protein in vaccines and field strains, allowing calculation of Epitope Content Comparison (EpiCC) scores reflecting the number of T-cell epitopes held in common. Previous work has shown that a bivalent PCV2a and PCV2b vaccine gave greater T cell epitope coverage (higher EpiCC scores) than either PCV2a or PCV2b as a monovalent, with the more complete match potentially helping to preserve or enhance vaccine efficacy. This study extends the above, using refined methodology to compare the putative T-cell epitope content of 4 PCV2 vaccines (3 based on PCV2a, and one a PCV2a and PCV2b bivalent) to a larger and more contemporary global sample of PCV2 field strains. 746 PCV2, ORF2 nucleotide sequences from diagnostic submissions dating from 2017 to 2021 were included. These comprised PCV2a (129), PCV2b (109) and PCV2d (508), and originated from Asia (185), Europe (269), North America (235) and South America (57). Phylogenetic classification confirmed the predominance of PCV2d in all regions, but with continuing presence of PCV2a and PCV2b. An interesting regional divergence was noted for PCV2a, with all strains from Europe grouped within a single phylogenetic cluster (cluster 10) and all but one from North America being in a different phylogenetic cluster (cluster 6). EpiCC scores for the bivalent vaccine were significantly higher than for the monovalents for all genotypes in all regions, showing the global relevance of the bivalent approach. Calculation of the relative contributions of the PCV2a and PCV2b components showed that, while most T-cell epitopes were present in both, each also made substantial unique contributions. Of most practical relevance, given that most commercial vaccines are based on PCV2a, the addition of PCV2b increased T-cell epitope coverage by 33% and 21% for PCV2b and PCV2d respectively.

The ability of influenza viruses to incessantly mutate makes these viruses to circulate in the field continuously. Every year, economic losses are faced by poultry industry due to vaccine failure. The current study was designed to bridge the gap by using various bioinformatics tools. For B-cells, HA protein of study virus showed 85.45% epitopes conservancy with vaccine 4 (local vaccine) whereas 54.54%, 67.27% and 43.63% were found conserved in vaccines 3, 2 and 1 (imported vaccines) respectively. For NA protein of study virus, 87.03% epitopes were found conserved in vaccine 4 whereas in vaccines 3, 2 and 1, 18.14%, 50% and 37.03% were found conserved respectively. Slight different results were obtained for T-cells. For MHC-1, vaccine 2 showed highest conservancy of 70% with HA protein of our study virus whereas, vaccine 1 and 3 showed 50% and vaccine 4 showed 60% conservancy. In case of NA protein 90%, 54%, 45% and 36% epitopes were conserved in vaccines 4, 3, 2 and 1 respectively against MHC-1 molecules. For MHC-2, HA protein of our study virus, vaccine 2 and 4 showed 84% conservancy whereas vaccine 1 and 3 showed 53% conservancy. While for NA protein, 100%, 28%, 71%, and 57% epitopes were conserved in vaccines 4, 3, 2 and 1 against MHC-2 molecules. In-vivo trials also supported in-silico results. Groups vaccinated with vaccine 1 and 3 respectively, showed significant levels of morbidity and post-challenge virus shedding through buccal and cloacal swab as compared to vaccine 2 and 4 respectively. Our study shows that there is a need of continuous evaluation and upgradation of seed virus of H9N2 vaccines, for this purpose in-silico analysis is a reliable and efficient method.

PIV 5 (Mammalian orthorubulavirus 5 - ICTV, 2021, previously known as Parainfluenza virus 5) is one of the main causes of ITB (infectious tracheobronchitis) affecting dogs, with a global distribution and potential to generate outbreaks from time to time. The currently available vaccines against the disease do not prevent the symptoms, require a high number of doses, and use adjuvants that, in addition to the cost of production, are responsible for adverse reactions, sometimes severe. Such drawbacks have raised the interest for new vaccine's development against ITB. In this context, we designed a recombinant immunogen based on the modified Vaccinia virus Ankara (MVA) expressing the hemagglutinin-neuraminidase (HN) envelope protein of PIV 5, and evaluated the immunogenic potential of this vaccine in C57BL/6 female mice. For the immunogenicity analyzes, epitopes of CD8⁺ T cell for the MHC-I murine alleles were predicted in silico, evaluated in vitro through flow cytometry and ELISA assays, and were used to evaluate the CD8⁺ T cell responses. The efficient expression of the envelope protein by the recombinant vector, allied to the immunogenic responses in vivo, highlights the potential of our recombinant MVA as a vaccine against PIV 5.

This study unveils immunodominant epitopes from the African Swine Fever Virus Major Capsid protein and created a multiepitope vaccine candidate. Protein sequences of 42 strains of ASFV from 28 countries were selected. Binding to MHC proteins were predicted. T and Linear B Lymphocytes epitopes were adopted and evaluated for antigenicity, immunogenicity, allergenicity, and toxicity. Selected epitopes were modelled and molecularly docked against the appropriate MHC proteins. An adjuvant and multiple linkers were used to create multiepitope vaccine candidate (VC). After evaluating the physicochemical and immunological properties of the vaccine candidate, its structure was refined, validated, and mutated. The Molecular Dynamics Simulation of the VC with the TLR4 receptor was performed and cloned in silico in a plasmid vector. A VC with 130 amino acid residues, 14.60 KDa weight and isoelectric point of 10.63 emerged. The VC is hydrophilic and non-allergenic; has MHC I immunogenicity and antigenicity values of 1.43 and 0.72 respectively, an instability index value of 33.11 and half-life of 1 h, 0.5 h and > 10 h in reticulocytes of mammals, yeast, and E. coli respectively. The VC shows good promise and further tests are required to determine its safety and efficacy.

Bovine Respiratory Disease (BRD) is a major cause of calfhood mortality. Bovine Respiratory Syncytial Virus (BRSV), Bovine Parainfluenza 3 Virus (BPIV3), Bovine Herpes Virus-1 (BHV-1), and Bovine Corona Virus (BCV) are major pathogens in BRD outbreaks.

The importance of early protection of newborn calves is undoubted. The BRD vaccines licensed in Europe can be applied from one or two weeks of age onwards. We have investigated the safety and immunity of a commercial intranasal live BRSV-BPIV3 combination vaccine and a live-attenuated BCV vaccine (in development) in calves at day of birth.

In the safety study the calves were revaccinated two weeks after the first vaccination. In the efficacy studies, the calves were experimentally infected with field isolates six days (BRSV, study #2), seven days (BPIV3, study #3) and five days (BCV, study #4), post vaccination.

Animals were monitored for any adverse effects of the vaccination and clinical disease following the challenge infection. Samples were collected and tested for RNA specific for the respective vaccine and challenge viruses. Fourteen days after the BRSV challenge infection, the animals in study #2 were euthanized and a necropsy was performed.

The frequency and degree of symptoms of abnormal health observed in the safety study, were comparable to those observed in older animals after vaccination with the same vaccines.

Mild to moderate signs of upper respiratory tract disease (URTD) were the predominant clinical signs after challenge infection. The average scores in the vaccinated groups were lower than in the control groups, but the differences did not reach statistical significance.

Moreover, the virus load in nasal swabs was significantly lower in the vaccinated group as was the BCV virus load in rectal swab samples taken from the vaccinated animals.

From the four studies it can be concluded that the vaccines used in these studies can be applied from the day of birth onwards.

Polyinosinic:polycytidylic acid or poly(I:C) is a double stranded RNA analog that is known for stimulating RNA sensing pathways in a variety of cell culture and animal models. Activation of nucleic acid sensing pathways lead to the up-regulation of Interferon-β which ultimately creates an antiviral state in the host. The involvement of intracellular DNA sensors in poly(I:C) mediated immune response has not been extensively explored. Poly(I:C) stimulates the intracellular DNA sensing in addition to RNA sensing pathways in buffalo fibroblasts. Genomic DNA leak into the cytosol due to poly(I:C) is likely to stimulate the intracellular DNA sensing pathways. The mRNA expression of DNA sensors cGAS, IFI16-L (IFI16-like) and DAI are elevated while DDX41 and STING are down-regulated in poly(I:C) treated cells. However, STING activation is evident in poly(I:C) treated cells through the formation of aggregates around the nucleus. IFI16-L also aggregates like STING and translocates from the nucleus to the cytoplasm in response to poly(I:C). The activation of DNA sensors by a dsRNA mimic indicates that mammalian cells can use their own molecules for defending themselves against pathogenic RNA viruses. This provides an opportunity to search for novel therapeutic targets against RNA viruses that evade detection by canonical pattern recognition receptors.

Foot-and-mouth disease (FMD) is an acute and highly contagious animal disease caused by foot-and-mouth disease virus (FMDV). The outbreaks of FMD have brought huge economic losses and the disease has been considered as one of the most harmful infectious diseases to animal husbandry. The invasion of FMDV can be recognized by host immune system and the activated immune responses are responsible for suppression of viral infection and clearance of the virus. In order to maintain fitness and host adaptation, various viruses have evolved multiple elegant strategies to antagonize host immune response. In this review, we elaborated the molecular mechanisms of regulating host immunity by FMDV. We hope this will provide insights for FMD vaccine design, and help prevent and control FMD.