Can novel oral polio vaccine type 2 (nOPV2) put us back on track towards global polio eradication?
Following global oral polio vaccine type 2 (OPV2) cessation in May 2016, monovalent OPV2 only remained stockpiled for outbreak response. As inactivated polio vaccine (IPV) induces only limited mucosal immunity mOPV2 was the only appropriate vaccine for stopping circulating vaccine derived poliovirus type 2 (cVDPV2) outbreaks. However, if an insufficient number of children are reached new circulating strains will be seeded, leading eventually to new outbreaks. In addition, if sufficient upscaling of IPV would not be achieved timely to meet the global need, the intestinal mucosal immunity to PV2 on population level would decrease in regions lacking this IPV supply, increasing the risk of cVDPVs and new paralytic polio cases. In order to meet these risks researchers developed new IPV and OPV vaccine candidates to address current and future needs. In 2011 a scientific consortium was established by the Bill & Melinda Gates Foundation with the objective to create more genetically stable, novel OPVs to support the Global Polio Eradication Initiative. The aim of this thesis was to evaluate two novel OPV2 (nOPV2) candidates in healthy adults for safety, immunogenicity, viral shedding and genetic stability (phase 1 and 2 studies) in order that further evaluation could be continued in children and infants in Panama. Also, the infrastructure that had to be built and all the procedures that were necessary to conduct the first in-human study in containment conditions in 2017 have been described. In addition, a novel adjuvanted IPV vaccine has been evaluated for safety, humoral immunogenicity and the ability to generate mucosal responses in comparison with IPV. In conclusion, in the presented studies both nOPV2 candidates show good safety and non-inferior immunogenicity in comparison with mOPV2. Also, these vaccines demonstrated enhanced genetic stability of shed viruses with low neurovirulence in animal testing and no reversion of domain V, the most dominant mutation site. These results have led to further testing in children and infants with ultimate selection and roll-out of the current nOPV2 vaccine. Addition of dmLT to IPV administered intramuscularly neither affected humoral nor intestinal immunity nor decreased fecal virus shedding following bOPV challenge. The tolerability of the dose of dmLT used in this study may allow higher doses to be investigated for impact on mucosal immunity.
Antwerp : University of Antwerp, Faculty of Medicine and Health Sciences , 2023
252 p.
Supervisor: Van Damme, Pierre [Supervisor]
Supervisor: Maertens, Kirsten [Supervisor]
Supervisor: Theeten, Heidi [Supervisor]
Supervisor: Veitch, Keith [Supervisor]
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Creation 22.09.2023
Last edited 27.09.2023
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