Immunogenicity of 1 or 2 Doses of bOPV in Chilean Infants Primed With IPV Vaccine

Summary

The rationale for this study (IPV 002ABMG) is to evaluate and compare three doses of IPV, two doses of IPV plus one bOPV, and one dose of IPV plus two doses of bOPV in order to provide evidence for better immunization policy making in regions of the world that must switch to use of IPV/bOPV schedules in the 2014-2015 time frame. The goal is to identify the best option optimizing humoral immune responses, intestinal immunity and thereby prevent community transmission as well as preventing VAPP. Specifically, the study seeks to show that both of the sequential regimens are equivalent (not-inferior) to the 3-dose IPV regimen in the seroconversion rates to both type 1 and type 3 poliovirus such that not more than 10% of subjects fall below the 95% confidence interval observed for the 3-dose IPV alone regimen and the geometric mean titers (GMTs) are no more than 2/3 logs less than those for the 3-dose IPV regimen. In addition, the study will evaluate by a novel method (poliovirus shedding index), the adequacy of IPV vaccines in inducing intestinal immunity, specifically by reducing the shedding of poliovirus type 2 after an OPV challenge. The hypotheses of the study are: * A 3-dose IPV/bOPV sequential schedule including 1 or 2 doses of bOPV is non-inferior in terms of types 1 and 3 seroconversion rates and GMTs to a 3-dose IPV schedule. * Two and possibly 1 IPV dose(s) provides significant seroconversion rates and GMTs to type 2 poliovirus and sufficient priming to induce a rapid immune response in the context of an oral challenge at 7 months of age. * Three, 2, and possibly 1 dose of IPV will induce intestinal immunity to poliovirus type 2 as measured by a combination of quantity of virus in stools and duration of shedding (shedding index). In addition to these 3 hypotheses, the study will explore the following hypothesis: • Co-administration of bOPV and rotavirus at 16 weeks of age (the second rotavirus dose) provides similar antirotavirus IgA seroconversion rates and GMCs compared to subjects receiving rotavirus vaccine together with IPV.

Timeline

Start

2013-04

Primary completion

2014-05

Completion

2014-06

Publications

• Background 1. Global Polio Eradication Initiative. Data and Monitoring: Polio this week. Available at http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx.http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx. Copyright 2010. Accessed 8/23/2012 2. Sixty-fifth World Health Assembly. Poliomyelitis: Intensification of the global eradication initiative. WHA 65.5, Agenda item 13.10; 26 May 2012. 3. Sabin, A B.
• Background 2. Sixty-fifth World Health Assembly. Poliomyelitis: Intensification of the global eradication initiative. WHA 65.5, Agenda item 13.10; 26 May 2012.
• Background Asturias EJ, Dueger EL, Omer SB, Melville A, Nates SV, Laassri M, Chumakov K, Halsey NA. Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants. J Infect Dis. 2007 Sep 1;196(5):692-8. doi: 10.1086/520546. Epub 2007 Jul 23.
• Background Minor PD. Polio eradication, cessation of vaccination and re-emergence of disease. Nat Rev Microbiol. 2004 Jun;2(6):473-82. doi: 10.1038/nrmicro906. No abstract available.
• Brickley EB, Wieland-Alter W, Connor RI, Ackerman ME, Boesch AW, Arita M, Weldon WC, O'Ryan MG, Bandyopadhyay AS, Wright PF. Intestinal Immunity to Poliovirus Following Sequential Trivalent Inactivated Polio Vaccine/Bivalent Oral Polio Vaccine and Trivalent Inactivated Polio Vaccine-only Immunization Schedules: Analysis of an Open-label, Randomized, Controlled Trial in Chilean Infants. Clin Infect Dis. 2018 Oct 30;67(suppl_1):S42-S50. doi: 10.1093/cid/ciy603.
• O'Ryan M, Bandyopadhyay AS, Villena R, Espinoza M, Novoa J, Weldon WC, Oberste MS, Self S, Borate BR, Asturias EJ, Clemens R, Orenstein W, Jimeno J, Ruttimann R, Costa Clemens SA; Chilean IPV/bOPV study group. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study. Lancet Infect Dis. 2015 Nov;15(11):1273-82. doi: 10.1016/S1473-3099(15)00219-4. Epub 2015 Aug 26.

Drugs

Indications