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NPJ Vaccines. 2019 Feb 27;4:12. doi: 10.1038/s41541-019-0106-8. eCollection 2019.

Recombinant measles vaccine expressing malaria antigens induces long-term memory and protection in mice.

Author information

1
1Viral Genomics and Vaccination, Institut Pasteur, CNRS UMR-3569, 28 rue du Dr Roux, 75015 Paris, France.
2
2Anti-infectious Biotherapies and Immunity, Institut de Recherche Biomédicale des Armées, 1 place du Général Valérie André, BP73 Brétigny-sur-Orge Cedex, France.
3
3Malaria Infection and Immunity, Institut Pasteur, CNRS UMR-3569, 28 rue du Dr Roux, 75015 Paris, France.
4
4Malaria Parasite Biology and Vaccines, Institut Pasteur, CNRS UMR-3569, 28 rue du Dr Roux, 75015 Paris, France.

Abstract

Following the RTS,S malaria vaccine, which showed only partial protection with short-term memory, there is strong support to develop second-generation malaria vaccines that yield higher efficacy with longer duration. The use of replicating viral vectors to deliver subunit vaccines is of great interest due to their capacity to induce efficient cellular immune responses and long-term memory. The measles vaccine virus offers an efficient and safe live viral vector that could easily be implemented in the field. Here, we produced recombinant measles viruses (rMV) expressing malaria "gold standard" circumsporozoïte antigen (CS) of Plasmodium berghei (Pb) and Plasmodium falciparum (Pf) to test proof of concept of this delivery strategy. Immunization with rMV expressing PbCS or PfCS induced high antibody responses in mice that did not decrease for at least 22 weeks post-prime, as well as rapid development of cellular immune responses. The observed long-term memory response is key for development of second-generation malaria vaccines. Sterile protection was achieved in 33% of immunized mice, as usually observed with the CS antigen, and all other immunized animals were clinically protected from severe and lethal Pb ANKA-induced cerebral malaria. Further rMV-vectored malaria vaccine candidates expressing additional pre-erythrocytic and blood-stage antigens in combination with rMV expressing PfCS may provide a path to development of next generation malaria vaccines with higher efficacy.

Conflict of interest statement

The authors declare no competing interests.

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