Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial

Abstract

Background: The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV.Methods: A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV- bOPV(I-B-B), cIPV-tOPV-tOPV (I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doseswere administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population.Results: Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI D ¡2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: ¡6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: ¡1.50%, 8.48%) between I-B-B and I-T-T and ¡2.32% (95% CI: ¡5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of ¡10%. Of 24 serious adverse events reported, no one was vaccine-related.Conclusions: The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without compromising the immunogenicity and safety in the Chinese population. The findings will be essential for policy formulation by national and global authorities to facilitate polio elimination.

Immunogenicity of New Primary Immunization Schedules With Inactivated Poliovirus Vaccine and Bivalent Oral Polio Vaccine for the Polio Endgame: A Review

“…The studies in Chile [ 7 ], India [ 8 ], and 4 Latin America countries [ 10 , 11 ] included groups that received bOPV + 2 IPV doses, each of which achieved seroconversion of ≥96% for type 2 and >99% for types 1 and 3 ( Table 2 ). The study in China [ 12 ] with patients given 2 IPV doses followed by a single bOPV achieved seroconversion rates of 94.2%, 82.6%, and 97.7% for types 1, 2, and 3, respectively.…”

“…In Pakistan, a birth dose of bOPV followed by bOPV at 6–10–14 weeks and 1 dose of IPV at 14 weeks produced low type 2 seroconversion rates (51.3%), possibly due to high levels of maternal antibodies at baseline and widespread (19.4%) passive exposure to circulating type 2 vaccine viruses confounding the impact of IPV at 14 weeks. In contrast, the Chile and China studies evaluating sequential schedules [ 7 , 12 ], where IPV was given at 8 or 10 weeks without concomitant bOPV, reported type 2 seroconversion rates of 77.4% and 55.8%, respectively. Studies that evaluated the 2-dose impact of IPV (India, Chile, Latin America) reported uniformly high seroconversion rates of ≥96% for type 2 ( Table 2 ).…”

“…Most testing for poliovirus and polio antibodies was performed at the Centers for Disease Control and Prevention [ 7 , 9–11 , 14 ] or a specialized global polio eradication network laboratory in India using similar protocols [ 8 ]. For the study conducted in China, samples were tested at the National Institutes for Food and Drug Control in China [ 12 ]; for 1 of the Bangladesh studies, samples were processed at the International Centre for Diarrhoeal Disease Research, Bangladesh [ 13 ].…”

Co-circulation of coxsackieviruses A-6, A-10, and A-16 causes hand, foot, and mouth disease in Guangzhou city, China

“…PV type 1-3, belonging to EV-C, is notable as the pathogen of poliomyelitis (polio) [17,43]. We observed that all the patients associated with PV presented typical clinical manifestation of HFMD, such as skin rashes on hands and feet, and the age with serotypes of the affected associated with the PV inoculation [44,45]. However, the vaccination records of eight patients were unclear and further studies are needed.…”

Immunogenicity of sequential poliovirus vaccination schedules with different strains of poliomyelitis vaccines in Chongqing, China: a cross-sectional survey

“…Vaccination with sIPV and wIPV were provided to infants as the first dose of polio vaccine routine schedule for free. Although studies have shown that sequential schedules of wIPV with bOPV [4][5][6][7] and sIPV with tOPV [8][9][10] are sufficient for immunization, the immunogenicity of sequential schedules of different virus strain IPVs with bOPV remains unclear. Differences in the vaccines or the populations might affect immunogenicity.…”