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Infectious diseases remain a main cause of sickness and death for young children and infants worldwide. Vaccinating infants against infectious disease is complicated by newborns' immature immune systems, the tendency of their immune systems to mount Th2-biased responses, and interference from maternal antibodies. Dr. Babiuk's team is working to develop new formulations of vaccines that can induce a long-lasting, balanced immune response in infants after a single-administration vaccination.
The project team is aiming to develop and evaluate novel vaccine formulations that contain CpG oligodeoxynucleotides (CpG ODN), host defense peptides (HDP), polyphosphazenes, or a combination of these adjuvants. Because whooping cough remains a devastating disease for infants in the developing world, the team has started its work by focusing on the antigen that causes the disease, Bordetella pertussis toxoid (PTd).
Investigators are working toward development of a vaccine formulation that could be delivered via the mucosal lining of the nose or mouth, stimulating immunity at the surfaces where most disease-causing agents enter the body. It is anticipated that these vaccine formulations also could be used in vaccines against other diseases that affect infants and young children. |
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| | | Identify optimal CpG ODN, HDP and PP as adjuvant candidates through in vitro studies | | | | | Confirm optimal CpG ODN, HDP and PP in vivo with template antigen | | | | | Define duration of immunity | | | | | Confirm efficacy of optimal CpG ODN, HDP and PP formulations in challenge model | | | | | Confirm efficacy of optimal formulation for additional antigens | | | | | Test effect of maternal antibodies on vaccine formulation efficacy | | | | | Increase transfer of maternal antibodies through mucosal immunization | | | | | Assess stability of identified formulations | | | | | Establish safety profile of the optimal vaccine delivery system | | | | | Develop a single-shot vaccination | | |
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| | | The team conducted in vitro screening of all of the targeted adjuvants alone and in combination in humans, mice and pigs. They found that in all three species, CpG ODN showed strong activity in stimulating the immune system, judged by the secretion of pro-inflammatory cytokines and maturation of dendritic cells. | | | | | The team screened HDPs in humans, mice and pigs and found they induced the expression of chemokines and cytokines, immune system chemicals involved in cell recruitment and immune activation. | | | | | Based on results from the in vitro screening, the investigators chose formulations of the adjuvants to test in mice and pigs. They found that both the addition of CpG ODN and polyphosphazenes significantly enhanced the humoral immune response against pertussis toxoid, and shifted immune response toward a Th1-type of response. The investigators detected strong immune responses after a single immunization. In addition, after intranasal vaccination using a combination of the antigen, polyphosphazene and CpG ODN, they observed mucosal immune responses. | | |
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| | G. Mutwiri et al., Vaccine 25(7):1204-1213. | | | J. Booth et al., Vet Immunol Immunopathol 2007, 115(1-2):24-34 | | | A. Nichani, et al., Vet Immunol Immunopathol 2007 115(3-4):357-68 | | | Gerdts, V., G.K. Mutwiri, S.K. Tikoo, and L.A. Babiuk. (2006). Veterinary Research 37: 487-510. | |
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| | | Dr. Volker Gerdts, University of Saskatchewan, Saskatoon Saskatchewan, Canada - CA | | | | | Dr. Peter Andersen, Staten Serum Institute, Seoul, Korea, Democratic People's Republic of - KP | | | | | Dr. Saul Tzipori, Tufts University, Massachusetts, United States - US | | | | | Simon Fraser University, British Columbia, Canada - CA | | |
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