Enhancing safety and efficacy of RNAi-based gene therapy for the treatment of chronic hepatitis B

Abstract

Background: Polio eradication is a global health priority and Pakistan is among last three endemic countries. Supplementary immunization activities (SIAs) with oral poliovirus vaccines are usually separated by four week intervals; however, shorter intervals have been used in security compromised areas and for rapid outbreak response. We assessed immunogenicity of monovalent type 1 oral poliovirus vaccines (mOPV1) administered at shorter than usual intervals in a cohort of infants in Karachi, Pakistan. Methods & Materials: A randomized controlled trial was conducted to compare immunogenicity of two doses of mOPV1 given at 7 or 14 day-intervals with standard 30 day interval. In addition, bivalentOPV1&3 (bOPV)was administered at 30-day interval. Birth trivalent OPV and two study OPV doses were administered and blood samples obtained at birth, six weeks of age and one month after the last OPV dose. Bloodwas tested for poliovirus neutralizing antibodies. Results: A total of 1009 newborns were enrolled, and 829 (82%) met eligibility criteria for randomization at 6 weeks; 554 (55%) were included in the per protocol analysis. Seroprevalence of poliovirus neutralizing antibodies for poliovirus type 1 after three doses of OPV was>95% for all arms. Among those who did not seroconvert after birth dose, no significant differences in seroconversion to poliovirus type 1 after two study OPV doses were found between study arms (75.0% [CI95%=65-83%] for mOPV1 given at 7 day interval, 75.0% [CI95%=65-83%] for mOPV1 at 14 day interval, 78.1% [CI95%=69-86%] for mOPV1 at 30 day interval and 72.6% [CI95%=63-81%] for bOPV at 30 day interval). Conclusion: We found no differences in immunogenicity of mOPV1 administered in shorter than standard intervals. These results provide the scientific justification for the expanded use of the short-interval strategy to rapidly increase population immunity, to control outbreaks, prevent importations, and in areas of conflict where limited window of access can be created. Funding: The World Health Organization