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Re-engineering a Nanoparticle Human Papillomavirus Prophylactic Vaccine Antigen Based on the Minor Capsid Protein L2

Yang, Fan

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Abstract

Human papillomavirus (HPV) is the main cause of cervical cancer, which represents a major global health burden. Despite their success, current commercial virus-like particle vaccines have certain limitations, in particular the virus type-restricted antibody responses and the need for intact cooling chains in vaccine distribution. Here, we employed self-assembling nanoparticles that display different epitopes of the HPV minor capsid protein L2. Presenting the L2 epitopes on a scaffold provided by thioredoxin of the archaeon Pyrococcus furiosus (Pf Trx) in combination with a nanoparticle super-scaffold of Pyrococcus furiosus ferritin and encapsulin results in an antigen able to induce broadly protective antibody response against oncogenic and non-oncogenic HPV types in a small animal model. Moreover, in mice this protection could last one year after immunization. Considering of the safety of the vaccine antigen scaffold, we confirmed there was no cross-reactivity of antibodies induce against human thioredoxin or human ferritin. Thus, the nanoparticle vaccine induces robust titers of neutralizing antibodies, which are broadly reactive and persistent also providing protection in an in vivo mouse challenge model.

Item Type: Dissertation
Supervisor: Rösl, Prof. Dr. Frank
Place of Publication: Heidelberg
Date of thesis defense: 23 July 2020
Date Deposited: 22 Sep 2020 06:45
Date: 2020
Faculties / Institutes: Medizinische Fakultät Heidelberg > Institut für Immunologie
Medizinische Fakultät Heidelberg > Department for Infectiology
Subjects: 570 Life sciences
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