Effective Vaccine Candidate Research Articles

Recombinant outer membrane protein C of Aeromonas salmonicida subsp. masoucida, a potential vaccine candidate for rainbow trout (Oncorhynchus mykiss)

Aeromonas salmonicida subsp. masoucida (ASM) is an important bacterial pathogen of salmonid fish, which can cause huge economic losses to the fish farming industry. In order to screen effective vaccine candidate proteins, four outer membrane proteins of ASM, including OmpA, OmpC, OmpK and OmpW, were selected and recombinantly expressed in Escherichia coli. The result of western blotting showed that these four recombinant proteins could be recognized by rainbow trout anti-ASM antibodies. The immune protective effects of the four rOMPs were also investigated, and the relative percentage survival (RPS) of rOmpA, rOmpC, rOmpK and rOmpW were 71.1%, 81.6%, 55.3% and 42.1%, respectively. The RPS of rOmpC was significantly higher than the other three rOMPs, so the immune responses of rainbow trout induced by rOmpC were further investigated. The results showed that vaccination with rOmpC could significantly induced the production of specific serum antibodies and proliferation of sIg + lymphocytes in peripheral blood. Meanwhile, RT-qPCR analysis showed that rOmpC could significantly enhance the expression of the MHC-II, TCR, CD4, CD8, IL-8 and IgM genes compared with the BSA immunized group. These results demonstrated that rOmpC could induce strong humoral immune response in rainbow trout and provided effective immune protection against ASM challenge, which indicated that OmpC is a promising vaccine candidate against Aeromonas salmonicida infection.

A Systematic Review and Meta-Analysis of Serotype Distribution of Streptococcus Pneumoniae in Iran: Practical Evidence to Optimizing Local Vaccination Protocols.

Little is known regarding the burden of predominant circulating serotypes of Streptococcus pneumoniae in Iran. Therefore, this study aimed to investigate the serotype distribution of pneumococcal diseases in Iran by using a comprehensive systematic review of available articles. ; Methods: A systematic literature search was carried out to identify papers published by Iranian authors in the Web of Science, PubMed, Scopus, Embase and Google Scholar electronic databases from January 2000 to December 2018. Then, eight publications that met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis software. ; Results: In total, three studies reported the distribution of S. pneumoniae serotypes among patients, two studies among healthy individuals, and three studies among both groups. Of those studies, serotype 19A/F (17.9%; 95% CI: 13.6-23.0) was the most circulating serotype followed by 23A/F (12.3%; 95% CI: 7.7-19.2), 6A/B (11.0%; 95% CI: 8.0-14.9), and 14 (8.8%; 95% CI: 5.8-13.2). In contrast, the lowest circulating serotype was 60 (0.02%; 95% CI: 0.0-1.2), 29 (0.07%; 95% CI: 0.01-5.0), and 36 (0.09%; 95% CI: 0.04-2.1). Meta-regression results showed that prevalence of serotype 23A/F significantly increased each year about 0.2% (95% CI: 0.1-0.3, P <0.001, tau2 <0.001). ; Conclusion: In the present study, it was found that over the last decade, the most prevalent serotypes in Iran were 19, 23, 6, and 14, respectively. These findings provide practical evidence to select effective pneumococcal vaccine candidates for the prevention of invasive diseases in Iranian patients and also to compare our situation with others.

Recombinant Erns-E2 protein vaccine formulated with MF59 and CPG-ODN promotes T cell immunity against bovine viral diarrhea virus infection

To obtain an effective vaccine candidate against bovine viral diarrhea virus (BVDV) disease which causes great economical loss in cattle industries, recombinant Erns-E2 protein vaccine containing MF59 and CPG-ODN adjuvants was prepared and assessed in this study. The recombinant plasmid (pET32a-Erns-E2) was constructed and transformed into BL21 (DE3) cells to produce Erns-E2 protein. We immunized mice with the MF59–and CPG-ODN–adjuvanted recombinant Erns-E2 protein, E2 protein, or Erns protein, respectively. To evaluate immunogenicity and efficacy of a vaccine-adjuvant combination, mice were challenged with BVDV BJ175170 strain after immunization. All adjuvanted vaccines elicited detectable humoral and cellular immune responses, the BVDV-specific antibody titers as well as interleukin 4 (IL-4) levels in sera of mice immunized with the recombinant Erns-E2 protein were higher than in those of mice immunized with either the recombinant Erns or E2 protein. Besides, immunization with the Erns-E2 vaccines induced higher percentage of CD4+IFN-γ+, CD8+IFN-γ+ T cells and CD3+TNF-α+ T cells compared with the other vaccines. More protective efficacy against BVDV infection was acquired in the mice treated with the recombinant Erns-E2 protein, as shown by a reduction of viremia and slight pathological changes compared with both the control mice and the other vaccinated mice. Our findings suggest that the use of the recombinant Erns-E2 protein vaccine formulated with MF59 and CPG-ODN adjuvants enhances T cell responses and viral control, which warrants the Erns-E2 protein vaccine-adjuvant combination could be as a vaccine strategy to against BVDV.

Novel Mutant Phospholipase D from Hemiscorpius lepturus Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom.

Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues—His12 and His48—into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD100 of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.

Plasmodium falciparum Serine Repeat Antigen 5 (PfSERA5): current vaccine candidate for Plasmodium falciparum malaria

Background: Most of the malaria cases are caused by Plasmodium falciparum infection. The prevalence of cases and high mortality rates due to malaria should be watched out globally. However, currently, efforts to prevent and treat malaria suffer obstacles due to resistance to insecticides and antimalarial drugs. For these reasons, other preventive measures are needed, such as vaccines. This study aims to review the Plasmodium falciparum Serine Repeat Antigen 5 (PfSERA5) as a potential candidate for Plasmodium falciparum malaria vaccine development. Methods: Of the 65 journals reviewed, 51 journals were found to be suitable as references for this paper. The keywords included in selected search engines are "malaria" "PfSERA5", "Plasmodium falciparum", and "malaria vaccine". Search results and studies show that the erythrocytic phase of the vaccine can fight malaria parasites that escape the liver stage while reducing or eliminating clinical symptoms. Data were analyzed and written in a narrative form.Results: PfSERA5 is an asexual erythrocytic stage antigen that accumulates in the parasitophorous vacuole. The PfSERA5, SE47 and SE36 (modified SE47) domains can induce the formation of antibodies that protect against falciparum malaria infection in vivo and in vitro. This protective mechanism, caused by PfSERA5 (anti-SE47 and anti-SE36) specific antibodies, occurs through inhibition of parasite growth and merozoite lysis. PfSERA5 also does not show antigenic variations and has limited polymorphism, so the probability of resistance can be reduced. Conclusion: Based on this, PfSERA5 has great potential as an effective erythrocytic phase vaccine candidate. However, further studies are needed regarding the toxicological and pharmacological properties of PfSERA5, both in vivo and in clinical settings.

A Heterologous Viral Protein Scaffold for Chimeric Antigen Design: An Example PCV2 Virus Vaccine Candidate.

Recombinant vaccines have low-cost manufacturing, regulatory requirements, and reduced side effects compared to attenuated or inactivated vaccines. In the porcine industry, post-weaning multisystemic disease syndrome generates economic losses, characterized by progressive weight loss and weakness in piglets, and it is caused by porcine circovirus type 2 (PCV2). We designed a chimeric antigen (Qm1) to assemble the main exposed epitopes of the Cap-PCV2 protein on the capsid protein of the tobacco necrosis virus (TNV). This design was based on the Cap-N-terminal of an isolated PCV2 virus obtained in Chile. The virus was characterized, and the sequence was clustered within the PCV2 genotype b clade. This chimeric protein was expressed as inclusion bodies in both monomeric and multimeric forms, suggesting a high-molecular-weight aggregate formation. Pigs immunized with Qm1 elicited a strong and specific antibody response, which reduced the viral loads after the PCV2 challenge. In conclusion, the implemented design allowed for the generation of an effective vaccine candidate. Our proposal could be used to express the domains or fragments of antigenic proteins, whose structural complexity does not allow for low-cost production in Escherichia coli. Hence, other antigen domains could be integrated into the TNV backbone for suitable antigenicity and immunogenicity. This work represents new biotechnological strategies, with a reduction in the costs associated with vaccine development.

Immune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development.

Vaccination is one of the most important prevention tools providing protection against infectious diseases especially in children below the age of five. According to estimates, more than 5 million lives are saved annually by the implementation of six standard vaccines, including diphtheria, hepatitis B, Haemophilus influenza type b, polio, tetanus and yellow fever. Despite these efforts, we are faced with challenges in developing countries where increasing population and increasing disease burden and difficulties in vaccine coverage and delivery cause significant morbidity and mortality. Additionally, the high cost of these vaccines is also one of the causes for inappropriate and inadequate vaccinations in these regions. Thus, developing cost-effective vaccine strategies that could provide a stronger immune response with reduced vaccination schedules and maximum coverage is of critical importance. In last decade, different approaches have been investigated; among which live bacterial vaccines have been the focus of attention. In this regard, probiotic lactic acid bacteria have been extensively studied as safe and effective vaccine candidates. These microorganisms represent the largest group of probiotic bacteria in the intestine and are generally recognised as safe (GRAS) bacteria. They have also attracted attention due to their immunomodulatory actions and their effective role as novel vaccine adjuvants. A significant property of these bacteria is their ability to mimic natural infections, while intrinsically possessing mucosal adjuvant properties. Additionally, as live bacterial vaccines are administered orally or nasally, they have higher acceptance and better safety, but also avoid the risk of contamination due to needles and syringes. In this review, we emphasise the role of probiotic Lactobacillus strains as putative oral vaccine carriers and novel vaccine adjuvants.

Enhanced efficacy of a multi-epitope vaccine for type A and O foot‑and-mouth disease virus by fusing multiple epitopes with Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist

Foot-and-mouth disease (FMD) is an acute, severe, and highly contagious disease that affects cloven-hoofed animals and can lead to serious economic losses and social effects. Therefore, a safe and effective subunit vaccine is required to prevent and control FMD. Dendritic cells (DCs) are a type of professional antigen presenting cell (APC). Immature DCs are typically stimulated by various adjuvants via immune receptors (e.g., toll-like receptor 4 [TLR4]), which activate DCs to induce their maturation. TLR4 has been well-established to induce both innate and adaptive immune responses to various external microbial or internal damage-related molecular patterns. In this study, the multi-epitope immunogen, HAO, of foot-and-mouth disease virus (FMDV) serotypes A and O was fused with the recombinant protein, heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist, to obtain a new recombinant fusion protein, termed HAO-HBHA. HAO-HBHA was found to be highly efficient at activating murine DCs by the TLR4 pathway, both in vitro and in vivo. HAO-HBHA elicited strong specific humoral immune responses detected with an ELISA and virus neutralizing antibody test (VNT). HAO-HBHA also elevated the cellular immune responses, as indicated by intracellular cytokine (e.g., IFN-γ, TNF-α, IL-4, IL-6, IL-10, and IL-12p70) expression in Th1 and Th2 cells. As a TLR4 agonist, HBHA has significant advantages for enhancing the immune efficacy of a FMDV serotype A and O bivalent multi-epitope vaccine. These findings provide a novel strategy for the development of a safe and effective multi-epitope vaccine candidate against FMDV and further extends the application of TLR agonist-based vaccine platforms.

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

Zika virus (ZIKV) reemergence poses a significant health threat especially due to its risks to fetal development, necessitating safe and effective vaccines that can protect pregnant women. Zika envelope domain III (ZE3) has been identified as a safe and effective vaccine candidate, however it is poorly immunogenic. We previously showed that plant-made recombinant immune complex (RIC) vaccines are a robust platform to improve the immunogenicity of weak antigens. In this study, we altered the antigen fusion site on the RIC platform to accommodate N-terminal fusion to the IgG heavy chain (N-RIC), and thus a wider range of antigens, with a resulting 40% improvement in RIC expression over the normal C-terminal fusion (C-RIC). Both types of RICs containing ZE3 were efficiently assembled in plants and purified to >95% homogeneity with a simple one-step purification. Both ZE3 RICs strongly bound complement receptor C1q and elicited strong ZE3-specific antibody titers that correlated with ZIKV neutralization. When either N-RIC or C-RIC was codelivered with plant-produced hepatitis B core (HBc) virus-like particles (VLP) displaying ZE3, the combination elicited 5-fold greater antibody titers (>1,000,000) and more strongly neutralized ZIKV than either RICs or VLPs alone, after only two doses without adjuvant. These findings demonstrate that antigens that require a free N-terminus for optimal antigen display can now be used with the RIC system, and that plant-made RICs and VLPs are highly effective vaccines targeting ZE3. Thus, the RIC platform can be more generally applied to a wider variety of antigens.

High crossreactivity of human T cell responses between Lassa virus lineages.

Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.

29-kDa: A Potential Candidate for Anti-Tick Vaccine Antigen Source as Immunogenic and Stage Reactive Targeting Hard-Bodied Hyalomma Ticks Ixodidae

The objective of present study is to develop a vaccine against Hyalomma hard-bodied tick and to analyze relevant experimental data on immunized indigenous horse breed Morna. Montanide (ISA-50) adjuvant-based vaccine induced significantly (pandlt;0.02) higher antibody titre through intradermal route with 99.98% vaccine efficacy. Humoral response was determined though indirect ELISA; where peak level of serum antibody was recorded after six weeks interval of post-immunization. Most of hematology and biochemical parameters remained consistent to normal reference values. Our report also indicates a significant percentage decline in the numbers of engorged ticks, eggs mass, eggs number and increased tick rejection. The animal travel history can promote tick burden and is a potential risk factor. Based on biological and hematological parameters, it is possible to conclude that 29-kDa antigen can be used as an effective antigen vaccine candidate to control tick infestation detected through humoral response.

Proteomic Analysis of Schistosoma mansoni Tegumental Proteins.

The tegument (outer surface) of Schistosoma mansoni and other trematodes is in intimate contact with the host and plays an important role in host-parasite interactions. It is a complex structure that contains hundreds of proteins implicated in a variety of functions, although, so far, only a few proteins have been well characterized. Indeed, a few of these proteins have been shown to be effective vaccine and diagnostic candidates against S. mansoni and other schistosomes, and so the proteomic characterization of tegumental molecules could open new avenues for the development of novel control and surveillance strategies to combat schistosomiasis. Here, we describe the step by step isolation of tegumental proteins from the different tegument compartments using a biotinylation approach, as well as the materials and reagents needed.

Immunogenicity of 987P fimbriae of enterotoxigenic Escherichia coli surface-displayed on Lactobacillus casei

As most pathogens invade the bodies through the mucosa, it is crucial to develop vaccines that induce mucosal immunity. To this end, we generated a safe and effective vaccine candidate that displayed fimbrial protein 987P of enterotoxigenic Escherichia coli (ETEC) on the surface of Lactobacillus casei (L.casei) CICC 6105 by using poly-γ-glutamate synthetase A (PgsA) as an anchoring matrix. After gavage inoculation of the recombinant strain pLA-987P/L.casei into specific-pathogen-free (SPF) BALB/c mice, high levels of mucosal immunoglobulin A (IgA) were induced in fecal samples, intestine and lung lavage fluids and systemic immunoglobulin G of IgG subclasses (IgG1, IgG2b, and IgG2a) was produced in serum. T-cell proliferation assays showed the stimulation index (SI) of the groups immunized with pLA-987P/L.casei to be significantly higher than that of the control group. The recombinant L.casei promoted T cells to produce both Th1 and Th2 cytokines, while the number of splenic IL-4 Spot forming cells (SFC) exceeded the number of IFN-γ SFC by 2.26-fold (P < .01). >83.3% of the vaccinated mice were protected from challenge with a lethal dose of virulent strain C83916. These results indicate that the recombinant L.casei expressing ETEC 987P fimbrial protein could elicit a protective immune response against ETEC 987P infection effectively.

Prophylactic potential of cytolethal distending toxin B (CdtB) subunit of typhoid toxin against Typhoid fever

Typhoid fever caused by Salmonella enterica serovar Typhi (S.Typhi) continues to be a major problem, especially in developing countries. Due to the rapid emergence of multi-drug-resistant (MDR) strains, which limits the efficacy of conventional antibiotics as well as problems associated with the existing vaccines, efforts are being made to develop effective prophylactic agents. CdtB subunit of typhoid toxin was selected for assessing its vaccine potential due to its high conservation throughout the Typhi strains. In-vitro assessment of DNase activity of cloned and purified CdtB protein showed a significant decrease in the band intensity of DNA. The measure of metabolic activity and morphological alterations assessed using different cell lines in the presence of CdtB protein showed no significant signs of toxicity. These observations were further strengthened by cell cycle analysis, assessed by flow cytometry. Keeping these observations in mind, the immunoprotective potential of CdtB was assessed using S.Typhi induced mouse peritonitis model. A significant titer of IgG antibodies (>128000) against CdtB protein was recorded in the immunized mice by enzyme-linked immunosorbent assay (ELISA), which was also validated by immunoblotting. Active immunization with the protein protected 75% mice against a lethal dose of S.Typhi Ty2. The data indicated a significant (up to 5 log) reduction in the bacterial load in the spleen and liver of immunized-infected mice compared to control (unimmunized-infected) mice which might have resulted in the modulation of histoarchitecture of spleen and liver and the levels of cytokines (IL-6, TNF-α and IL-10) production; thereby indicating the effectiveness of the subunit. The observations deduced from the study give the proof of concept of immunogenic potential of protein. However, further studies involving the immunoreactivity of CdtB with the statistically significant number of sera samples obtained from the human patients would be helpful in establishing the relevance of CdtB protein in humans and for making the strategies to develop it as an effective vaccine candidate.

In silico design and in vitro analysis of a recombinant trivalent fusion protein candidate vaccine targeting virulence factor of Clostridium perfringens

Necrotic enteritis (NE) is a multifactorial disease in broiler that is caused by colonization of Clostridium perfringens in their gastrointestinal tract. Recently several immunogenic proteins from virulent C. perfringens have been considered as vaccines to provide protection against NE. In this study, a novel trivalent fusion protein including immunogenic epitopes of three virulence factors of, NetB, alpha toxin and a metallopeptidase protein (NAM) was designed using in silico studies. Circular dichroism spectra was applied for determination of secondary structure and folding properties of the purified recombinant NAM (rNAM) expressed in E. coli. The antigenicity of rNAM was confirmed by induction of immune response in rabbit and neutralization experiments of the toxins in cell culture studies. To this end, anti-rNAM antisera neutralized the crude toxins produced by a wild type virulent C. perfringens strain using chicken hepatocellular carcinoma (LMH) cell lines. The cells were exposed to a mixture of anti-rNAM antisera and 2 × LD50 doses of the toxins. The result showed 94% viability of the cells against the crude toxins, in the presence of anti-rNAM antisera. Our study suggests that combination of metallopeptidase protein along with alpha toxin and NetB toxins is a potent immunogen which is able to neutralize the toxicity of crude extracellular toxins. The recombinant chimeric NAM could be a suitable and effective subunit vaccine candidate to prevent NE disease caused by C. perfringens.

A Marker-Free Bordetella bronchiseptica aroA/bscN Double Deleted Mutant Confers Protection Against Lethal Challenge.

Bordetella bronchiseptica is a leading cause of swine respiratory disorders which depict a great threat to well-flourished porcine industry. Vaccination remains an effective way for the prevention of B. bronchiseptica infections, as live B. bronchiseptica vaccines possess many advantages compared to inactivated vaccines and/or sub-unit vaccines, however, their safety is not up to the mark. In present study, we constructed marker-free aroA/bscN double deleted B. bronchiseptica QH09 through two-step homologous recombination strategy. Our data showed that QH09 attenuated virulence to mice compared with the parent aroA deleted B. bronchiseptica QH0814. We also found that QH09 meets the vaccine safety standards, upon challenge in piglets, did not cause any visible clinical signs or lesions on organs. Finally, we demonstrated that vaccination of QH09 activated the systemic as well as the mucosal immunity in pigs and provided protection against lethal bacterial challenge. These findings suggest that the aroA/bscN double deleted B. bronchiseptica QH09 may be an effective vaccine candidate, with safety assurance of animals against B. bronchiseptica infections.

A novel vaccine platform using glucan particles for induction of protective responses against Francisella tularensis and other pathogens.

SummaryVaccines are considered the bedrock of preventive medicine. However, for many pathogens, it has been challenging to develop vaccines that stimulate protective, long‐lasting immunity. We have developed a novel approach using β‐1,3‐D‐glucans (BGs), natural polysaccharides abundantly present in fungal cell walls, as a biomaterial platform for vaccine delivery. BGs simultaneously provide for receptor‐targeted antigen delivery to specialized antigen‐presenting cells together with adjuvant properties to stimulate antigen‐specific and trained non‐specific immune responses. This review focuses on various approaches of using BG particles (GPs) to develop bacterial and fungal vaccine candidates. A special case history for the development of an effective GP tularaemia vaccine candidate is highlighted.

Prediction and validation of potent peptides against herpes simplex virus type 1 via immunoinformatic and systems biology approach.

The human herpes simplex virus type 1 (HSV-1) is an extremely rampant human pathogen, and its infection could cause life-long diseases, including the central nervous system disorders. The glycoproteins of HSV-1 such as glycoprotein B, glycoprotein C, glycoprotein D, glycoprotein H, and glycoprotein L are highly involved in mediating the viral attachment and infection of the host cell. Therefore, immunoinformatic approaches followed by molecular dynamics simulation and systems biology has been used to analyze these glycoproteins in order to propose effective peptide-based vaccine candidates against the HSV-1 infection. The ElliPro and NetCTL.1.2 online tools were employed to forecast the B- and T-lymphocyte (CTL) epitopes for gB, gC, gD, gH, and gL. The 3D coordinates of these epitopes were modeled and docked against the human major histocompatibility complex molecule-1. The outcomes obtained from postdocking analysis along with TAP (Transporter associated with antigen processing), MHC binding, and C-terminal cleavage score assisted in the selection of potential epitopes. These epitopes were further subjected to molecular dynamics simulation and systems biology approach which showed significant results. On the basis of these substantial outcomes, peptides are proposed that could be used to provoke immunity against the HSV-1 infection.

Pathogenesis of Hypervirulent Fowl Adenovirus Serotype 4: The Contributions of Viral and Host Factors.

Since 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS), caused by hypervirulent fowl adenovirus serotype 4 (FAdV-4), have emerged in several provinces in China, posing a great threat to poultry industry. So far, factors contributing to the pathogenesis of hypervirulent FAdV-4 have not been fully uncovered. Elucidation of the pathogenesis of FAdV-4 will facilitate the development of effective FAdV-4 vaccine candidates for the control of HHS and vaccine vector. The interaction between pathogen and host defense system determines the pathogenicity of the pathogen. Therefore, the present review highlights the knowledge of both viral and host factors contributing to the pathogenesis of hypervirulent FAdV-4 strains to facilitate the related further studies.

Neosporosis: An Overview of Its Molecular Epidemiology and Pathogenesis

Abstract Neospora caninum (N. caninum), a cyst-forming protozoan parasite, is a major cause of bovine abortions and neonatal mortality worldwide. N. caninum has a broad intermediate host range, and its sexual cycle occurs exclusively in canids. Another species of Neospora, Neospora hughesi (N. hughesi), has been identified and causes myeloencephalitis in horses. Although molecular epidemiology studies are in their infancy, the 18S ribosomal RNA (rRNA) and ITS1 regions within the small subunit ribosomal RNA (ssuRNA) and an N. caninum species-specific DNA probe (pNc5) have been used extensively to differentiate Neospora from other closely related apicomplexan parasites. While these repetitive regions have higher sensitivity and specificity than housekeeping or antigen genes, they suffer from low discriminatory power and fail to capture intra-species diversity. Similarly, although multiple minisatellite or microsatellite marker studies have shown clear geographic substructures within Neospora, strains are often misclassified due to a convergence in the size of different alleles at microsatellite loci, known as homoplasy. Only one strain, N. caninum Liverpool (Nc-Liv), has been genome sequenced and compared with its closest relative, Toxoplasma gondii (T. gondii). Hence, detailed population genomics studies based on whole-genome sequences from multiple strains worldwide are needed in order to better understand the current population genetic structure of Neospora, and ultimately to determine more effective vaccine candidates against bovine neosporosis. The aim of this review is to outline our current understanding of the molecular epidemiology and genomics of Neospora in juxtaposition with the closely related apicomplexan parasites Hammondia hammondi and T. gondii.