Superior protection conferred by inactivated whole virus vaccine over subunit and DNA vaccines against salmonid alphavirus infection in Atlantic salmon (Salmo salar L.)

Salmonid alphavirus 3 (SAV-3) is an emerging pathogen in Norwegian salmon farming and causes severe annual losses. We studied the immunogenicity and protective ability of subunit and DNA vaccines based on E1 and E2 spike proteins of salmonid alphavirus subtype 3 (SAV-3), and compared these to an experimental inactivated, whole virus (IWV) vaccine in Atlantic salmon. The antigens were delivered as water-in-oil emulsions for the subunit and inactivated vaccines and non-formulated for the DNA vaccines. The IWV and the E2 subunit prime-boost groups had circulating neutralizing antibodies at challenge, correlating with high protection against lethal challenge and 3-log(10) reduction of virus titer in heart for the IWV group. Prime-boost with E1 subunit vaccine also conferred significant protection against mortality, but did not correlate with neutralizing antibody levels. Protection against pathology in internal organs was only seen for the IWV group. Prime-boost with E1 and E2 DNA vaccines showed marginal protection in terms of reduction of viral replication in target organs and protection against mortality was not different from controls. The IWV group showed significant upregulation of IFNγ and IL2 mRNA expression at 4 weeks post challenge possibly indicating that other mechanisms in addition to antibody responses play a role in mediating protection against infection. This is the first report comparing the immunogenicity and protection against mortality for IWV vaccines and spike protein subunit and DNA vaccines against salmonid alphavirus infection in Atlantic salmon. The IWV vaccine has superior immunogenicity over sub-unit and DNA vaccines.     

Immunogenicity and clinical protection against equine influenza by DNA vaccination of ponies

Equine influenza A (H3N8) virus infection is a leading cause of respiratory disease in horses, resulting in widespread morbidity and economic losses. As with influenza in other species, equine influenza strains continuously mutate, often requiring the development of new vaccines. Current inactivated (killed) vaccines, while efficacious, only offer limited protection against diverse subtypes and require frequent boosts. Research into new vaccine technologies, including gene-based vaccines, aims to increase the neutralization potency, breadth, and duration of protective immunity. Here, we demonstrate that a DNA vaccine expressing the hemagglutinin protein of equine H3N8 influenza virus generates homologous and heterologous immune responses, and protects against clinical disease and viral replication by homologous H3N8 virus in horses. Furthermore, we demonstrate that needle-free delivery is as efficient and effective as conventional parenteral injection using a needle and syringe. These findings suggest that DNA vaccines offer a safe, effective, and promising alternative approach for veterinary vaccines against equine influenza.     

Novel approaches to whole sporozoite vaccination against malaria

The parasitic disease malaria threatens more than 3 billion people worldwide, resulting in more than 200 million clinical cases and almost 600,000 deaths annually. Vaccines remain crucial for prevention and ultimately eradication of infectious diseases and, for malaria, whole sporozoite based immunization has been shown to be the most effective in experimental settings. In addition to immunization with radiation-attenuated sporozoites, chemoprophylaxis and sporozoites (CPS) is a highly efficient strategy to induce sterile protection in humans. Genetically attenuated parasites (GAP) have demonstrated significant protection in rodent studies, and are now being advanced into clinical testing. This review describes the existing pre-clinical and clinical data on CPS and GAP, discusses recent developments and examines how to transform these immunization approaches into vaccine candidates for clinical development.     

Duration of the protective immune response after prime and booster vaccination of yearlings with a live modified cold-adapted viral vaccine against equine influenza

We previously created a live vaccine against equine influenza based the new reassortant cold-adapted (Ca) strain A/HK/Otar/6:2/2010. The live vaccine contains surface proteins (HA, NA) from the wild-type virus A/equine/Otar/764/2007 (Н3N8; American Lineage Florida Clade 2), and internal proteins (PB2, PB1, PA, NP, M, NS) from the attenuated Ca donor virus A/Hong Kong/1/68/162/35CA (H3N2). To determine the safety and duration of the protective immune responses, 90 yearlings were intranasally vaccinated in single mode, double mode at an interval of 42 days (10^7.0 EID₅₀/animal for both vaccinations), or with PBS (control group). Ten animals from each group were challenged with the homologous wild-type virus A/equine/Otar/764/07 (Н3N8) at 1, 2, 3, 4, 5, 6, 9 and 12 months after vaccination. Similarly, 10 animals from each group were challenged with the heterologous wild-type virus A/equine/Sydney/2888-8/07 (Н3N8; American Lineage Florida Clade 1) 12 months after vaccination. The vaccine was completely safe, and single intranasal vaccination of yearlings was capable of inducing statistically significant (from P = 0.03 to P < 0.0001) clinical and virological protection against the homologous virus; however, only double mode vaccination generated significant (from P = 0.02 to P < 0.0001) protection against the heterologous virus at 12 months (observation period). Interestingly, this vaccine enables the differentiation of infected and vaccinated animals. On this basis of this study, we recommend double intranasal administration of this vaccine at an interval of 42 days in veterinary practice.