Viral Immunology

Sow immunity plays an important role in preventing viral infection and disease in newborn piglets. Vertical transmission of porcine circovirus type 2 (PCV2) may perpetuate porcine circovirus associated disease (PCVAD) in newborn and growing pigs. Hence, the immunological effects of maternal immunoglobulin transfer of PCV2-specific antibodies on PCV2 viremia and immune response in piglets in commercial swine herds were evaluated. Sow vaccination has been shown to reduce viral shedding and viremia, and increases the neutralizing antibody (NA) titers...

Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix(®). A substitution of the 2009 nucleoprotein for the 1934 variant has been implicated in narcolepsy development. The aims were to determine (a) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (NP-CA2009) and Pandemrix-[A/Puerto Rico/8/1934(H1N1)] (NP-PR1934) nucleoproteins in 43 patients and 64 age-matched controls; (b) antibody affinity in reciprocal competitive assays in 11 childhood narcolepsy patients compared with 21 age-matched controls; and (c) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (H1N1 NS1), not a component of the Pandemrix vaccine...

Detection of respiratory syncytial virus (RSV) in blood, including mononuclear leukocytes and organs other than the lung, suggests that RSV disseminates outside the respiratory tract. In this study, the role of platelets in host defense against RSV was explored using an in vitro model. Platelets, also produced in the lungs, are increasingly recognized as an important part of host immune responses and may therefore play a role in modulating lung infections and clearing RSV viremia. In human peripheral blood mononuclear cells (PBMCs), platelets significantly reduced RSV infection of monocytes, monocyte activation, and interferon (IFN)α/γ production...

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, dehydration in pigs, and high mortality rates in piglets <3 weeks of age. Maternal immunity protects piglets, but information on vaccination before or after natural infection in endemically exposed sow herds is limited. Currently, the recovery goal in sow units infected with PEDV is to become fully naive again or use natural virus infection to develop immune gilts through a feedback program before introduction into the sow herd. Since neutralizing antibodies in the gut are critical for protection against enteric viral infections such as PEDV, we evaluated the effect of a conditionally licensed, adjuvanted inactivated PEDV vaccine on neutralizing antibody levels in milk and colostrum in both naive and previously naturally exposed sow herds...

Immunological memory is elicited after either vaccination or natural exposure to a pathogen and is essential for protection against re-exposure. Despite its critical importance, the ability to interrogate the veterinary animal memory immune response has long been hindered by a paucity of tools to assess immunological memory. As a result, the evaluation and analysis of protective immune responses that predict immune protection in food and fiber animals and facilitate vaccine development are obstructed. To fill this gap in knowledge in swine, we created a B cell tetramer to porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 7 (nsp7) to efficiently and effectively investigate the memory B cell response, a hallmark of anti-viral immunity...

Hepatitis C virus (HCV) infection represents a worldwide health problem and has been for long an attractive point of research due to diversity among different genotypes regarding unique geographical distribution and diverse treatment outcome. HCV is considered a major cause of chronic liver disease and cirrhosis, which leads to liver failure and hepatocellular carcinoma requiring liver transplantation. Of the HCV genotypes identified, HCV genotype 4 (HCV-4) is the least studied. HCV-4 is responsible for ∼10% of HCV infections and is common in the Middle East and Africa; recently it is increasingly prevalent in European Countries...

Commercial broiler and layer chickens are heavily vaccinated against economically important viral diseases with a view of preventing morbidity, mortality, and production impacts encountered during short production cycles. Hatchery vaccination is performed through in ovo embryo vaccination prehatch or spray and subcutaneous vaccinations performed at the day of hatch before the day-old chickens are being placed in barns with potentially contaminated environments. Commercially, multiple vaccines (e.g., live, live attenuated, and viral vectored vaccines) are available to administer through these routes within a short period (embryo day 18 prehatch to day 1 posthatch)...

The objective of this study was to develop a new antigen delivery system using an alphavirus replicon particle (RP) to induce humoral antibody responses against bovine viral diarrhea virus (BVDV) recombinant antigen produced from envelope glycoprotein E2. An alphavirus RP expressing the E2 glycoprotein of BVDV was used for immunization of pigs. A fluorescent microsphere immunoassay (FMIA) has been applied to detect BVDV E2 antigen-specific antibody isotype in pig immunized with alphavirus RP. Full-length BVDV E2 (aa 1-375) was cleaved into several pieces, eight E2 DNA fragments, including full-length DNA, were cloned into expression vector pHUE, and the recombinant proteins expressed in BL-21 (DE3) Escherichia coli...

Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...

To evaluate the association of the -308 and -238 tumor necrosis factor alpha (TNF-α) gene polymorphisms with clinical manifestations of dengue and TNF-α serum levels in a northwestern Mexican population. The study populations included dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, and a group of healthy controls (HCs) without history of dengue. Polymerase chain reaction-restriction fragment length polymorphism and Enzyme-Linked Immunosorbent Assay were performed to determine genotypes and serum concentration of TNF-α, respectively...

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Vaccines are essential tools for the prevention and control of infectious diseases in animals. One of the most important steps in vaccine development is the selection of a suitable adjuvant. The focus of this review is the adjuvants used in vaccines for animals. We will discuss current commercial adjuvants and experimental formulations with attention to mineral salts, emulsions, bacterial-derived components, saponins, and several other immunoactive compounds. In addition, we will also examine the mechanisms of action for different adjuvants, examples of adjuvant combinations in one vaccine formulation, and challenges in the research and development of veterinary vaccine adjuvants...

A meta-analysis of CD4+ T cell epitope maps reveals clusters and gaps in envelope-protein (E protein) immunogenicity that can be explained by the likelihood of epitope processing, as determined by E protein three-dimensional structures. Differential processing may be at least partially responsible for variations in disease severity among arbo-flaviruses and points to structural features that modulate protection from disease.

Intravenous immunoglobulin (IVIG) is used to treat or prevent severe viral infection, especially cytomegalovirus (CMV) infections. IVIG was characterized to understand its interaction with CMV-infected cells. IVIG retarded CMV spread and reduced virus yields depending on the neutralizing (NT) antibody titer. Immediate early protein synthesis was reduced by IVIG in 3 to 15 h, and IVIG specifically reduced the ratio of 66/68k protein synthesis among immediate early proteins in an NT antibody-dependent manner between 4 and 8 h after infection, indicating that antigenic modulation of CMV-infected cells by IVIG reduced viral protein synthesis and virus production...

Despite effective measles vaccines, measles still causes severe morbidity and mortality worldwide, particularly in developing countries. The Th2 pathway involving interleukin (IL)-4 and IL-13 cytokines, and their receptor IL-4Rα, play important roles in the Th1/Th2 balance and antibody production. A Th2 skewing of the cytokine milieu may affect vaccine responses. We investigated IL-4, IL-13, and IL-4Rα polymorphisms and their impact on measles IgG responses and measles vaccine failure, in two separate cohorts: 12-month-old Australian children immunized with measles-mumps-rubella vaccine (n = 137) and a case/control cohort of children aged 6 months-14 years from Mozambique, Africa (n = 89), some of whom were vaccinated, but still contracted measles (vaccine failure)...

Superoxide dismutase 2 (SOD2) is essential in radical scavenging, which balances the intracellular level of reactive oxygen species (ROS). The dysfunction of SOD2 is associated with increasing incidence of various human diseases, including cancer, neuron diseases, and myocardial defects. However, the connections between SOD2-mediated oxidative homeostasis and innate immune response remain unclear. In this study, we report that SOD2 is a crucial regulator of antiviral signaling. Depletion of SOD2 impairs RNA virus-induced type I interferon (IFN) and proinflammatory cytokine production, resulting in enhanced viral replication...

Adaptive B cell response is a key arm of protective immunity against influenza viruses. Owing to the acutely infectious and cytopathic nature of these viruses, efficient containment of viral spread relies on the prompt provision of protective antibodies to the site of virus infection, the respiratory tract (RT). To accelerate the protective antibody response, B cell responses can be ectopically induced, maintained, and reactivated in the lungs after primary and secondary infection, thereby providing an anatomical advantage in supplying neutralizing antibodies against reinfecting viruses with faster kinetics...

Highly pathogenic avian influenza (HPAI) H5N1 virus emerged in 1997 as a zoonotic disease in Hong Kong. It has since spread to Asia and Europe and is a serious threat to both the poultry industry and human health. For effective surveillance and possible prevention/control of HPAI H5N1 viruses, it is necessary to understand the molecular mechanism underlying HPAI H5N1 pathogenesis. The hemagglutinin (HA) protein of influenza A viruses (IAVs) is one of the major determinants of host adaptation, transmissibility, and viral virulence...

The effect of the current influenza vaccine, an inactivated virus vaccine administered by subcutaneous/intramuscular injection, is limited to reducing the morbidity and mortality associated with seasonal influenza outbreaks. Intranasal vaccination, by contrast, mimics natural infection and induces not only systemic IgG antibodies but also local secretory IgA (S-IgA) antibodies found on the surface of the mucosal epithelium in the upper respiratory tract. S-IgA antibodies are highly effective at preventing virus infection...

The lung is an important line of defense that is exposed to respiratory infectious pathogens, including viruses. Lung epithelial cells and/or alveolar macrophages are initially targeted by respiratory viruses. Once respiratory viruses invade the cells of the lung, innate immunity is activated to inhibit viral replication. Innate immune signaling also activates virus-specific adaptive immune responses. The helper T cells play pivotal roles in the humoral and cellular adaptive immune responses. Helper T cells are categorized into several distinct subsets (e...