Salmonid Double-stranded RNA-Dependent Protein Kinase Activates Apoptosis and Inhibits Protein Synthesis.

dsRNA-dependent protein kinase R (PKR) is a key factor of innate immunity. It is involved in translation inhibition, apoptosis, and enhancement of the proinflammatory and IFN responses. However, how these antiviral functions are conserved during evolution remains largely unknown.

Unexpected regulatory functions of cyprinid Viperin on inflammation and metabolism.

Background: Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune response against a wide array of viruses. In mammals, Viperin exerts its antiviral function through enzymatic conversion of cytidine triphosphate (CTP) into its antiviral analog ddhCTP as well as through interactions with host proteins involved in innate immune signaling and in metabolic pathways exploited by viruses during their life cycle. However, how Viperin modulates the antiviral response in fish remains largely unknown.

Immediate-early protein of equid herpesvirus type 1 as a target for cytotoxic T-lymphocytes in the Thoroughbred horse.

Cytotoxic T-lymphocytes (CTLs) are associated with protective immunity against disease caused by equid herpesvirus type 1 (EHV-1). However, the EHV-1 target proteins for CTLs are poorly defined. This limits the development of vaccine candidates designed to stimulate strong CTL immunity.

Safety and serological response to a matrix gene-deleted rabies virus-based vaccine vector in dogs.

Dogs account for the majority of human exposures and deaths due to rabies virus (RABV) worldwide. In this report, we show that a replication-deficient RABV-based vaccine in which the matrix gene is deleted (RABV-ΔM) is safe and induces rapid and potent VNA titers after a single inoculation in dogs. Average VNA titers peaked at 3.

Domestic goose as a model for West Nile virus vaccine efficacy.

West Nile virus (WNV) is an emergent pathogen in the Americas, first reported in New York during 1999, and has since spread across the USA, Central and South America causing neurological disease in humans, horses and some bird species, including domestic geese. No WNV vaccines are licensed in the USA for use in geese. This study reports the development of a domestic goose vaccine efficacy model, based on utilizing multiple parameters to determine protection.

Accelerated vaccination schedule provides protective levels of antibody and complete herd immunity to equine influenza.

Reasons For Performing Study: During the 2007 Australian equine influenza (EI) outbreak, an accelerated primary course 14 day intervaccination schedule was proposed, but not widely implemented. Expert opinion was divided as to the efficacy of such a schedule given the lack of published data. This study determined the level and duration of humoral immunity following administration of a recombinant canarypox-vectored vaccine (ALVAC-EIV) with a primary intervaccination interval of 14 days and booster at 105 days.

An African horse sickness virus serotype 4 recombinant canarypox virus vaccine elicits specific cell-mediated immune responses in horses.

A recombinant canarypox virus vectored vaccine co-expressing synthetic genes encoding outer capsid proteins, VP2 and VP5, of African horse sickness virus (AHSV) serotype 4 (ALVAC(®)-AHSV4) has been demonstrated to fully protect horses against homologous challenge with virulent field virus. Guthrie et al. (2009) detected weak and variable titres of neutralizing antibody (ranging from <10 to 40) 8 weeks after vaccination leading us to hypothesize that there could be a participation of cell mediated immunity (CMI) in protection against AHSV4.

Evaluation of the response to an accelerated immunisation schedule using a canarypox-vectored equine influenza vaccine, shortened interdose intervals and vaccination of young foals.

The results of an accelerated immunisation schedule for horses used as part of the emergency response plan to contain and eradicate equine influenza in Australia in 2007 is described. The horses studied were vaccinated with a recombinant canarypox-vectored vaccine (ProteqFlu®, Merial) with a shorter interdose interval. Vaccinated horses included foals aged less than 4 months.

Protection provided by a recombinant ALVAC(®)-WNV vaccine expressing the prM/E genes of a lineage 1 strain of WNV against a virulent challenge with a lineage 2 strain.

The emergence of lineage 2 strains of WNV in Europe as a cause of clinical disease and mortality in horses raised the question whether the existing WNV vaccines, all based on lineage 1 strains, protect against circulating lineage 2 strains of WNV. In the present paper we have determined the level of cross protection provided by the recombinant ALVAC(®)-WNV vaccine in a severe challenge model that produces clinical signs of WNV type 2 disease. Ten horses were vaccinated twice at 4 weeks interval with one dose of the ALVAC-WNV vaccine formulated at the minimum protective dose.

Humoral and cell-mediated immune responses of old horses following recombinant canarypox virus vaccination and subsequent challenge infection.

Equine influenza virus is a leading cause of respiratory disease in the horse population; however, the susceptibility of old horses to EIV infection remains unknown. While advanced age in horses (>20 years) is associated with age-related changes in immune function, there are no specific recommendations regarding the vaccination of older horses even though a well-characterized effect of aging is a reduced antibody response to standard vaccination. Therefore, we evaluated the immunological and physiological response of aged horses to a live non-replicating canarypox-vectored EIV vaccine and subsequent challenge infection.

Onset and duration of immunity to equine influenza virus resulting from canarypox-vectored (ALVAC) vaccination.

Equine influenza virus remains an important problem in horses despite extensive use of vaccination. Efficacy of equine influenza vaccination depends on the onset and duration of protective immunity, and appropriate strain specificity of the immune response. This study was designed to test the protective immunity resulting from vaccination with the North American commercial ALVAC equine influenza vaccine (RECOMBITEK Influenza, Merial, USA)(1) against challenge with American lineage influenza viruses.

Protective immunization of horses with a recombinant canarypox virus vectored vaccine co-expressing genes encoding the outer capsid proteins of African horse sickness virus.

We describe the development and preliminary characterization of a recombinant canarypox virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant canarypox virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contrast, a horse immunized with a commercial recombinant canarypox virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness.

Onset and duration of protective immunity against clinical disease and renal carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine.

Protection against clinical disease and prevention of the renal carrier state remain the key objectives of vaccination against leptospirosis in the dog. In the present paper, groups of dogs were vaccinated twice with a commercial bacterin (EURICAN L) containing Leptospira interrogans serovars icterohaemorrhagiae and canicola and challenged with heterologous representatives of both serovars at 2 weeks (onset of immunity) or 14 months (duration of immunity) after the second vaccination. Control dogs were not vaccinated against leptospirosis and kept with the vaccinated dogs.

Comparison of antibody responses after vaccination with two inactivated rabies vaccines.

Thirty laboratory dogs were randomly assigned to two groups (A and B) of 15 dogs and subcutaneously vaccinated with a single dose of one of two commercially available monovalent inactivated rabies vaccines: RABISIN (Merial, France) (group A) and NOBIVAC Rabies (Intervet International) (group B). Rabies antibodies were measured over a period of 4 months using the fluorescent antibody virus neutralization (FAVN) test. The two vaccines performed differently in terms of magnitude and persistence of rabies antibodies titers in dogs.

A West Nile virus (WNV) recombinant canarypox virus vaccine elicits WNV-specific neutralizing antibodies and cell-mediated immune responses in the horse.

Successful vaccination against West Nile virus (WNV) requires induction of both neutralizing antibodies and cell-mediated immune responses. In this study, we have assessed the ability of a recombinant ALVAC-WNV vaccine (RECOMBITEK WNV) to elicit neutralizing antibodies and virus-specific cell-mediated immune responses in horses. In addition, we examined whether prior exposure to ALVAC-WNV vaccine would inhibit B and cell-mediated immune responses against the transgene product upon subsequent booster immunizations with the same vaccine.

New assays to measure equine influenza virus-specific Type 1 immunity in horses.

Equine influenza virus (EIV) is a leading cause of respiratory disease in horses. Equine influenza infection induces a long-term immunity to re-infection. Recent strategies of vaccination aim to mimic this immunity by stimulating both antibody and cellular immune responses.

Effective priming of foals born to immune dams against influenza by a canarypox-vectored recombinant influenza H3N8 vaccine.

A classical limitation of early life immunization is the interference by maternally derived antibodies, which are known to inhibit the immune response to modified-live and killed vaccines. Several studies have convincingly shown that even minute amounts of maternally derived antibodies against equine influenza can strongly interfere with successful vaccination of foals born to immune mares. In this study we evaluated the response of foals born to vaccinated mares to immunization with a canarypox-vectored recombinant vaccine against equine influenza virus H3N8.

Efficacy of a canarypox-vectored recombinant vaccine expressing the hemagglutinin gene of equine influenza H3N8 virus in the protection of ponies from viral challenge.

Objective: To determine onset and duration of immunity provided by a 2- or 3-dose series of a new canarypox-vectored recombinant vaccine for equine influenza virus (rCP-EIV vaccine) expressing the hemagglutinin genes of influenza H3N8 virus strains A/eq/Kentucky/94 and A/eq/Newmarket/2/93 in ponies.

Animals: Forty-nine 1- to 3-year-old male Welsh Mountain Ponies that were seronegative for equine influenza virus.

Procedures: Vaccinated and control ponies were challenged with aerosolized influenza virus A/eq/Sussex/89 (H3N8), representative of the Eurasian lineage of circulating influenza viruses.

Development and registration of recombinant veterinary vaccines. The example of the canarypox vector platform.

The canarypox vaccine vector (ALVAC) technology has been used to develop and license several vaccines for companion animals and horses in the European Union and USA. ALVAC is a ubiquitous vector with high biosafety since it is non-replicative in mammalians, is genetically and physically stable, and able to induce both humoral and cell-mediated immune responses against the expressed transgene product. Specific rules apply for the development and registration of recombinant vector vaccines.

Evaluation of the efficacy provided by a Recombinant Canarypox-Vectored Equine West Nile Virus vaccine against an experimental West Nile Virus intrathecal challenge in horses.

Efficacy of the Recombitek Equine West Nile Virus (WNV) vaccine was evaluated against a WNV intrathecal challenge model that results in WNV-induced clinical disease. Ten vaccinated (twice at days 0 and 35) and 10 control horses were challenged 2 weeks after administration of the second vaccine with a virulent WNV by intrathecal administration. After the challenge, eight of 10 controls developed clinical signs of encephalomyelitis whereas one vaccinate exhibited muscle fasciculation only once.

A molecular approach to the identification of cytotoxic T-lymphocyte epitopes within equine herpesvirus 1.

Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes (CTL) show reduced severity of respiratory disease and frequency of abortion, probably by CTL-mediated control of cell-associated viraemia. This study aimed to identify CTL epitopes restricted by selected major histocompatibility complex (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3 haplotype.

Antibody and IFN-gamma responses induced by a recombinant canarypox vaccine and challenge infection with equine influenza virus.

In horses, equine influenza virus (EIV) is a leading cause of respiratory disease. Conventional inactivated vaccines induce a short-lived immune response. By comparison, natural infection confers a long-term immunity to re-infection.

Pathogenesis of West Nile virus infection in dogs treated with glucocorticoids.

Control and glucocorticoid-treated dogs were infected with West Nile virus (WNV) through the bites of infected mosquitoes to study the effect of a commonly used immunomodulator on the magnitude and duration of viremia and on development of clinical disease. All dogs became viremic after challenge. The peak viremia and integrated magnitude of viremia were approximately 40 and 50 times higher, respectively, in the five dogs treated with methyl-prednisolone for 1 month compared with untreated dogs.