ABSTRACT
This Commentary article reviews the history of veterinary immunology in Australia from the 1980s and discusses the key people and areas of research during this period.
Subject(s)
Allergy and Immunology , Veterinary Medicine , Australia , Veterinary Medicine/history , Allergy and Immunology/history , History, 20th CenturySubject(s)
Blood Coagulation Disorders/diagnosis , Cardiopulmonary Resuscitation/methods , Military Medicine/methods , Monitoring, Physiologic/methods , Thrombelastography/methods , Wounds and Injuries/therapy , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , Cardiopulmonary Resuscitation/mortality , Critical Care/methods , Female , Humans , Male , Mass Casualty Incidents/mortality , Mass Casualty Incidents/statistics & numerical data , Point-of-Care Systems , Quality Improvement , Risk Assessment , Severity of Illness Index , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/mortality , Shock, Hemorrhagic/therapy , Survival Analysis , Trauma Severity Indices , United Kingdom , Warfare , Wounds and Injuries/complications , Wounds and Injuries/mortalityABSTRACT
DNA vaccines have proven to be an efficient means of inducing immune responses in small laboratory animals; however, their efficacy in large out-bred animal models has been much less promising. In addressing this issue, we have investigated the ability of ovine cytotoxic lymphocyte antigen 4 (CTLA-4) mediated targeting and ruminant specific CpG optimised plasmids, both alone and in combination, to enhance immune responses in sheep to the pro cathepsin B (FhCatB) antigen from Fasciola hepatica. In this study, CTLA-4 mediated targeting enhanced the speed and magnitude of the primary antibody response and effectively primed for a potent memory response compared to conventional DNA vaccination alone, which failed to induce a detectable immune response. While the CpG-augmentation of the CTLA-4 targeted construct did not further enhance the magnitude or isotype profile of the CTLA-4 induced antibody titres, it did result in the induction of significant antigen-specific, lymphocyte-proliferative responses that were not observed in any other treatment group, showing for the first time that significant cellular responses can be induced in sheep following DNA vaccination. In contrast, CpG-augmentation in the absence of CTLA-4 mediated targeting failed to induce a detectable immune response. This is the first study to explore the potential adjuvant effects of ruminant specific CpG motifs on DNA vaccine induced immune responses in sheep. The ability of CpG-augmented CTLA-4 mediated targeting to induce both humoral and cellular immune responses in this study suggests that this may be an effective approach for enhancing the efficacy of DNA vaccines in large out-bred animal models.
Subject(s)
Adjuvants, Immunologic , Antigens, Differentiation/physiology , Antigens, Helminth/immunology , Cathepsin B/immunology , CpG Islands/immunology , Fasciola hepatica/immunology , Vaccines, DNA/immunology , Animals , Antigens, CD , COS Cells , CTLA-4 Antigen , Chlorocebus aethiops , Immunoglobulin G/blood , Immunoglobulin G/classification , Immunologic Memory , Lymphocyte Activation , Plasmids , Sheep , VaccinationABSTRACT
DNA vaccination, delivered through various routes, has been used extensively in laboratory animals. Few studies have focused on veterinary species and while results obtained in laboratory animals can often be extrapolated to veterinary species this is not always the case. In this study we have compared the effect of the route of immunisation with DNA on the induction of immune responses and protection of sheep to challenge with live Corynebacterium pseudotuberculosis. Intramuscular injection of plasmid DNA encoding an inactivated form of the phospholipase D (PLD) antigen linked to CTLA4-Ig resulted in the induction of a strong memory response and sterile immunity following challenge in 45% of the animals. In contrast, gene gun delivery or subcutaneous (SC) injection of the DNA vaccine induced comparatively poor responses and insignificant levels of protection. Thus, DNA vaccine efficacy in sheep is strongly influenced by the route of vaccination. Amongst intramuscular vaccinates, protected sheep had significantly elevated IgG2 responses compared to unprotected animals, while both subgroups had equivalent IgG1 levels. This suggests that the presence of IgG2 antibodies and hence a Th1-like response, induced by the DNA vaccine gave rise to protective immunity against C. pseudotuberculosis.
