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Review A review of the role of CpG oligodeoxynucleotides as toll-like receptor 9 agonists in prophylactic and therapeutic vaccine development in infectious diseases. 2008
Gupta K, Cooper C. · Division of Infectious Diseases, University of Ottawa, Ottawa, Ontario, Canada. · Drugs R D. · Pubmed #18457466 No free full text.
Abstract: This article reviews the biology of Toll-like receptors, the current understanding of the mechanism by which CpG oligodeoxynucleotides (ODNs) perturb immune function and the published literature describing their evaluation in the development of vaccines in humans. The role of these molecules as immune modulators in HCV treatment is also considered. There has been considerable research evaluating the role of CpG ODNs as an adjuvant and immune modulator in hepatitis B, hepatitis C and influenza. The safety and immunogenicity of the 1018 ISS compound in combination with Engerix-B was assessed in 99 healthy, adult seronegative volunteers. One month following the first immunization dose, 78.7% in the rHBsAg plus 1018 ISS group versus 11.8% in the Engerix-B group achieved protective titres. One hundred percent of rHBsAg plus 1018 ISS and 18.0% of hepatitis B vaccine-alone recipients were seroprotected 1 week following the second dose of study vaccine. After all doses of vaccine had been administered, seroprotection rates were 100% and 64%, respectively (p < 0.001). CPG 7909 was co-administered with Engerix-B in 56 healthy adults. After the second injection (week 6 time point), seroprotection was achieved in 100% of CPG 7909 recipients (0.5 mg 13/13; 1.0 mg 12/12; 0.125 mg 12/12) compared with 55% (6/11) of control participants (p = 0.0003). Twelve months post prime, all subjects who had received the full course of vaccination maintained seroprotective anti-HBs titres. The safety and immunogenicity of Engerix B plus CPG 7909 was assessed in HIV seropositive patients. All CPG 7909 recipients (n = 19) and 17/19 (89%) control subjects achieved seroprotection by 2 weeks after the third and final injection (10 weeks). Seroprotective titres remained in all CPG 7909 recipients at 48 weeks (100%) versus 12/19 (63%) for controls (p = 0.008). This cohort of HIV-infected patients was followed at 6-month intervals for up to 60 months after enrolment. The difference in seroprotection (> or =10 mIU/L) and GMT between study arms remained significant (p < 0.05) at all time points from month 24 to month 60. There is great potential for CpG ODN as vaccine adjuvants and as therapeutic immune modulators. The use of these molecules as a hepatitis B vaccine adjuvant is most promising.
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Article Effects of a brief educational program on knowledge and willingness to accept treatment among patients with hepatitis C at inner-city hospitals. 2007
Gupta K, Romney D, Briggs M, Benker K. · Department of Preventive Medicine and Community Health, Division of Hepatology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 43, Brooklyn, NY 11203, USA. · J Community Health. · Pubmed #17696047 No free full text.
Abstract: Hepatitis C is the most common cause of chronic liver disease in the United States. The prevalence of HCV infection is higher in African Americans and Hispanics than among non-Hispanic whites. African Americans not only have a high prevalence of HCV but they also show lower response rates to treatment with pegylated interferon and Ribavirin. Studies have shown that HCV patients often have low levels of knowledge about the disease, including knowledge about modes of transmission and available treatment options. This study was based in two inner-city hospitals in Brooklyn, New York, Kings County Medical Center and The University Hospital of Brooklyn. The goal of this study was to evaluate the change in knowledge of patients with HCV and their willingness to accept treatment after a single session of on-site education which was delivered as part of a clinic visit. Our patients were from minority ethnic groups, with the majority being African Americans. There was a substantially low knowledge among patients with HCV about the etiologic agent being a virus amongst the twenty five patients who completed the study. After the educational intervention there was an increase in knowledge about risk factors for transmitting HCV, such as unprotected sexual intercourse (100% vs. 88% at baseline), tattooing and body piercing (88% vs. 64% at baseline), and sharing personal items like razors. Knowledge of the risk of developing liver cancer in patients with HCV also increased substantially (96% vs. 77% at baseline). There was a marked increase in the expressed willingness to accept treatment (88% vs. 41% baseline). The results of the educational intervention were very encouraging. These results have implication in setting up a structured educational intervention in liver clinics for HCV patients.
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