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Adenovirus-prime and baculovirus-boost heterologous immunization achieves sterile protection against malaria sporozoite challenge in a murine model.

Published version
Peer-reviewed

Type

Article

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Authors

Yoshida, Kunitaka 
Iyori, Mitsuhiro 
Blagborough, Andrew M 
Dulal, Pawan 

Abstract

With the increasing prevalence of artemisinin-resistant malaria parasites, a highly efficacious and durable vaccine for malaria is urgently required. We have developed an experimental virus-vectored vaccine platform based on an envelope-modified baculovirus dual-expression system (emBDES). Here, we show a conceptually new vaccine platform based on an adenovirus-prime/emBDES-boost heterologous immunization regimen expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). A human adenovirus 5-prime/emBDES-boost heterologous immunization regimen consistently achieved higher sterile protection against transgenic P. berghei sporozoites expressing PfCSP after a mosquito-bite challenge than reverse-ordered or homologous immunization. This high protective efficacy was also achieved with a chimpanzee adenovirus 63-prime/emBDES-boost heterologous immunization regimen against an intravenous sporozoite challenge. Thus, we show that the adenovirus-prime/emBDES-boost heterologous immunization regimen confers sterile protection against sporozoite challenge by two individual routes, providing a promising new malaria vaccine platform for future clinical use.

Description

Keywords

Adenoviridae, Adenoviridae Infections, Animals, Antibodies, Protozoan, Antigens, Protozoan, Baculoviridae, Disease Models, Animal, Female, Immunization, Immunization, Secondary, Malaria, Malaria Vaccines, Malaria, Falciparum, Mice, Mice, Inbred BALB C, Plasmodium falciparum, Protozoan Proteins, Sporozoites, Vaccination, Vaccines, DNA

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/N00227X/1)