Thesis (Ph.D.)--The Pennsylvania State University, 2001. / Includes bibliographical references.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) have been shown to stimulate the innate immune system against a variety of bacterial, viral, and protozoan infections in a variety of vertebrate species. The objectives of this study were to investigate the immunostimulatory effect of CpG-ODN against Salmonella Typhimurium infection and the formulation and delivery of CpG-ODN by the in ovo route. Day-old broiler chicks or embryonated eggs (day 18th of incubation) received either 50 g of CpG-ODN, 50 g of non-CpG-ODN, or saline. At day four-post hatch, all birds were subcutaneously inoculated by Salmonella Typhimurium. Clinical signs, pathology, bacterial isolations from the air sacs, and mortality were observed for ten days following challenge. The survival rate of the birds that received CpG-ODN via in ovo or in vivo treatments was significantly higher than the control group. Salmonella Typhimurium level in the peripheral blood and pathology were significantly lower (p < 0.001) in CpG-ODN group compared to the control group. In order to investigate the effect of formulation of CpG-ODN, embryonated eggs (day 18th of incubation) were inoculated with either 50 g of CpG-ODN alone or CpG-ODN formulated with polyphosphazene, liposome, or Emulsigen®. Four days after administration of CpG-ODN formulations, the birds were challenged with E. coli by subcutaneous injection. Clinical signs, pathology, bacterial isolations from the air sacs, and mortality were observed for seven days following challenge. The birds that received either CpG-ODN or CpG-ODN formulated with polyphosphazene had significantly higher survival rates (30 and 60%) compared to the birds in groups receiving either non-CpG-ODN or saline. Bacterial loads in the air sacs were lower in groups treated with formulated CpG-ODN compared to the CpG-ODN alone or control groups. However, formulation of CpG-ODN with liposomes or Emulsigen® did not increase the immunoprotective effect against E. coli infection. We showed that treatment with CpG-ODN protects neonatal chickens against an intracellular bacterial infection and that co-treatment of CpG-ODN with polyphosphazene enhances the immunoprotective effect of CpG-ODN.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) have been shown to stimulate the innate immune system against a variety of bacterial, viral, and protozoan infections in a variety of vertebrate species. The objectives of this study were to investigate the immunostimulatory effect of CpG-ODN against Salmonella Typhimurium infection and the formulation and delivery of CpG-ODN by the in ovo route. Day-old broiler chicks or embryonated eggs (day 18th of incubation) received either 50 g of CpG-ODN, 50 g of non-CpG-ODN, or saline. At day four-post hatch, all birds were subcutaneously inoculated by Salmonella Typhimurium. Clinical signs, pathology, bacterial isolations from the air sacs, and mortality were observed for ten days following challenge. The survival rate of the birds that received CpG-ODN via in ovo or in vivo treatments was significantly higher than the control group. Salmonella Typhimurium level in the peripheral blood and pathology were significantly lower (p < 0.001) in CpG-ODN group compared to the control group. In order to investigate the effect of formulation of CpG-ODN, embryonated eggs (day 18th of incubation) were inoculated with either 50 g of CpG-ODN alone or CpG-ODN formulated with polyphosphazene, liposome, or Emulsigen®. Four days after administration of CpG-ODN formulations, the birds were challenged with E. coli by subcutaneous injection. Clinical signs, pathology, bacterial isolations from the air sacs, and mortality were observed for seven days following challenge. The birds that received either CpG-ODN or CpG-ODN formulated with polyphosphazene had significantly higher survival rates (30 and 60%) compared to the birds in groups receiving either non-CpG-ODN or saline. Bacterial loads in the air sacs were lower in groups treated with formulated CpG-ODN compared to the CpG-ODN alone or control groups. However, formulation of CpG-ODN with liposomes or Emulsigen® did not increase the immunoprotective effect against E. coli infection. We showed that treatment with CpG-ODN protects neonatal chickens against an intracellular bacterial infection and that co-treatment of CpG-ODN with polyphosphazene enhances the immunoprotective effect of CpG-ODN.

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No description available.

As respiratory syncytial virus (RSV) is a respiratory pathogen that causes significant morbidity and mortality in infants, there has always been great interest in the development of a vaccine. In the 1960s, children were immunized with formalin-inactivated (FI)-RSV vaccines. Not only did these vaccines fail to prevent infection, but in most cases they resulted in enhanced disease upon subsequent exposure to the virus. In the intervening years, studies in mice have led to the hypothesis that the enhanced disease is due to an aberrant Th2-biased immune response. Thus, we hypothesized that formulating FI-RSV vaccines with a Th1 promoting adjuvant, such as CpG oligoeoxynucleotides (ODN), would result in the induction of protective immunity against RSV without risk of deleterious effects. We observed in calves that parenterally delivered FI-bovine RSV (BRSV) formulated with CpG ODN resulted in a shift towards a Th1-biased or more balanced immune response that was protective against BRSV.<p> As RSV infects the lung mucosa, vaccines that induce mucosal immunity are desirable. Parenterally delivered vaccines typically induce systemic immunity with low mucosal immune response levels, whereas mucosally delivered vaccines induce systemic and mucosal immunity. However, upon mucosal delivery there is an increased chance of vaccine components being degraded or washed away prior to the induction of immunity. Thus, we added polyphosphazenes (PP) to our mucosal vaccine formulations. PP are synthetic polymers that form non-covalent complexes with other vaccine components, increasing their stability. Intranasally delivered FI-BRSV co-formulated with CpG ODN and PP performed better than FI-BRSV alone, or FI-BRSV formulated with either adjuvant individually, in terms of inducing protective immunity against BRSV in mice. Furthermore, mice that received intranasally-delivered FI-BRSV or BRSV F protein co-formulated with CpG ODN and PP developed higher levels of immunity and protection than mice that received parenterally delivered vaccines. Because of the similarities between BRSV and HRSV, co-formulation of intranasally delivered HRSV vaccines with CpG ODN and PP could prove important in the development of a safe vaccine against HRSV in humans.

As respiratory syncytial virus (RSV) is a respiratory pathogen that causes significant morbidity and mortality in infants, there has always been great interest in the development of a vaccine. In the 1960s, children were immunized with formalin-inactivated (FI)-RSV vaccines. Not only did these vaccines fail to prevent infection, but in most cases they resulted in enhanced disease upon subsequent exposure to the virus. In the intervening years, studies in mice have led to the hypothesis that the enhanced disease is due to an aberrant Th2-biased immune response. Thus, we hypothesized that formulating FI-RSV vaccines with a Th1 promoting adjuvant, such as CpG oligoeoxynucleotides (ODN), would result in the induction of protective immunity against RSV without risk of deleterious effects. We observed in calves that parenterally delivered FI-bovine RSV (BRSV) formulated with CpG ODN resulted in a shift towards a Th1-biased or more balanced immune response that was protective against BRSV.<p> As RSV infects the lung mucosa, vaccines that induce mucosal immunity are desirable. Parenterally delivered vaccines typically induce systemic immunity with low mucosal immune response levels, whereas mucosally delivered vaccines induce systemic and mucosal immunity. However, upon mucosal delivery there is an increased chance of vaccine components being degraded or washed away prior to the induction of immunity. Thus, we added polyphosphazenes (PP) to our mucosal vaccine formulations. PP are synthetic polymers that form non-covalent complexes with other vaccine components, increasing their stability. Intranasally delivered FI-BRSV co-formulated with CpG ODN and PP performed better than FI-BRSV alone, or FI-BRSV formulated with either adjuvant individually, in terms of inducing protective immunity against BRSV in mice. Furthermore, mice that received intranasally-delivered FI-BRSV or BRSV F protein co-formulated with CpG ODN and PP developed higher levels of immunity and protection than mice that received parenterally delivered vaccines. Because of the similarities between BRSV and HRSV, co-formulation of intranasally delivered HRSV vaccines with CpG ODN and PP could prove important in the development of a safe vaccine against HRSV in humans.

No description available.

No description available.

No description available.