Administration of Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and Avian Beta Defensin as Adjuvants in Inactivated Inclusion Body Hepatitis Virus and its Hexon Protein-Based Experimental Vaccine Formulations in Chickens.

Inclusion body hepatitis (IBH) is one of the major infectious diseases adversely affecting the poultry industry of the United States and Canada. Currently, no effective and safe vaccine is available for the control of IBH virus (IBHV) infection in chickens. However, based on the excellent safety and immunogenic profiles of experimental veterinary vaccines developed with the use of new generation adjuvants, we hypothesized that characterization of vaccine formulations containing inactivated IBHV or its capsid protein hexon as antigens, along with poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and avian beta defensin 2 (ABD2) as vaccine adjuvants, will be helpful in development of an effective and safe vaccine formulation for IBH. Our data demonstrated that experimental administration of vaccine formulations containing inactivated IBHV and a mixture of PCEP with or without ABD2 as an adjuvant induced significantly higher antibody responses compared with other vaccine formulations, while hexon protein-based vaccine formulations showed relatively lower levels of antibody responses. Thus, a vaccine formulation containing inactivated IBHV with PCEP or a mixture of PCEP and ABD2 (with a reduced dosage of PCEP) as an adjuvant may serve as a potential vaccine candidate. However, in order to overcome the risks associated with whole virus inactivated vaccines, characterization of additional viral capsid proteins, including fiber protein and penton of IBHV along with hexon protein in combination with more new generation adjuvants, will be helpful in further improvements of vaccines against IBHV infection.

Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization.

Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immuno adjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system.

Effect of premolar and molar occlusal angle on feed digestibility, water balance, and fecal particle size in horses.

OBJECTIVE: To determine whether occlusal angle of the premolar and molar teeth (ie, molar occlusal angle) was associated with feed digestibility, water balance, or fecal particle size in adult horses. DESIGN: Observational study. ANIMALS: 40 pregnant mares ranging from 3 to 19 years old. PROCEDURE: The horses were randomly allocated to 1 of 5 feeding groups with 8 horses/group. Horses were sedated, and molar occlusal angle was measured with 2 methods. An oral examination was performed, and total number of dental abnormalities was recorded. Feed digestibility, water balance, and fecal particle size were measured 7 and 16 weeks later. RESULTS: Molar occlusal angle ranged from 6.3 degrees to 19.3 degrees and was not significantly associated with feed digestibility, water balance, or fecal particle size. The number of dental abnormalities was not associated with feed digestibility. Molar occlusal angle did not vary significantly with horse age. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that molar occlusal angles between 6 degrees and 19 degrees do not adversely affect feed digestibility, water balance, or fecal particle size in adult horses. Additionally, there was no association between age and molar occlusal angle.

Effect of dental floating on the rostrocaudal mobility of the mandible of horses.

OBJECTIVE: To evaluate the effect of dental floating on the position of the mandible relative to the maxilla (a measure of rostrocaudal mobility [RCM] of the mandible) during extension and flexion of the head of horses. DESIGN: Randomized controlled blinded trial. ANIMALS: 59 horses housed in 1 barn. PROCEDURE: Horses were formally randomized into a treatment (n = 33) or control (26) group. All horses were sedated, and the distance between rostral portions of the upper and lower incisor arcades were determined with the head fully extended and flexed at the poll (the difference in measurements represented the RCM of the mandible). The oral cavity was examined. For the treatment group, dental floating was performed, and the incisor arcade measurements were repeated. RESULTS: Dental correction resulted in a significant increase in RCM of the mandible in 31 of 33 horses. The mobility was greater in heavy horses than that detected in other breed classifications. Age and number of dental lesions did not significantly affect mobility before or after dental floating. CONCLUSIONS AND CLINICAL RELEVANCE: Dental floating increased RCM of the mandible, but measurement of this variable was not an indicator of the number or extent of dental lesions, and no specific dental abnormality appeared to significantly affect RCM of the mandible in horses. In horses, measurement of RCM of the mandible can be used as a guide to determine whether dental correction is necessary; after dental floating, it can be used to ensure that irregularities of the occlusal surface have been corrected.

Effect of dental floating on weight gain, body condition score, feed digestibility, and fecal particle size in pregnant mares.

OBJECTIVE: To investigate the effect of routine dental floating on weight gain, body condition score, feed digestibility, and fecal particle size in pregnant mares fed various diets. DESIGN: Randomized controlled clinical trial. ANIMALS: 56 pregnant mares. PROCEDURE: Mares were randomly allocated to 1 of 4 feed groups (n = 14 mares/group). All horses were sedated and an oral examination was performed, after which dental floating was performed on 7 horses in each group. Body weight was measured, and a body condition score was assigned before and at various times for 24 weeks after dental floating. Feed digestibility and fecal particle size were analyzed 7 and 19 weeks after dental floating. RESULTS: Weight gain, change in body condition score, feed digestibility, and fecal particle size were not significantly different between horses that underwent dental floating and untreated control horses. In contrast, weight gain was significantly associated with feed group. In the control horses, neither the number of dental lesions nor the presence of any particular type of lesion at the time of the initial oral examination was significantly associated with subsequent feed digestibility. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dental floating does not result in significant short-term changes in body weight, body condition score, feed digestibility, or fecal particle size in healthy pregnant mares. Further studies are necessary to determine the clinical utility of regular dental floating in apparently healthy horses.

Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigens.

We investigated the ability of a novel polyphosphazene polyelectrolyte, poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) to enhance antigen-specific immune responses. BALB/c mice were immunized once subcutaneously with either bovine serum albumin (BSA) or influenza virus X:31 antigen alone, or in combination with PCEP, or either of the adjuvants poly[di(sodium carboxylatophenoxy)phosphazene] (PCPP) and alum. Both PCEP and PCPP significantly enhanced serum antigen-specific total IgG, IgG1 and IgG2a antibody titers, and these responses were highest in PCEP-immunized mice. Alum induced only a modest enhancement of antibody responses. Reducing the dose of X:31 antigen by 25-fold had no effect on antibody responses in mice immunized with PCPP and PCEP, but resulted in reduced titers in those immunized with alum. Analysis of X:31 antigen-specific cytokines revealed that alum and PCPP were associated with a predominantly IL-4 response. In contrast, PCEP was associated with production of both IFNgamma and IL-4. We conclude that PCEP is a potent enhancer of antigen-specific Th1 and Th2 immune responses and is a promising adjuvant for vaccine applications.