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Review
, 53 (5), 733-740

Vaccine Platform Recombinant Measles Virus

Affiliations
Review

Vaccine Platform Recombinant Measles Virus

Michael D Mühlebach. Virus Genes.

Abstract

The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

Keywords: Emerging infections; Life-attenuated vector; Measles virus; Reverse genetics; Vector platform.

Conflict of interest statement

The author declares no potential conflict of interest. The author is supported by the German Center for Infection Research (DZIF; TTU 01.802).

Figures

Fig. 1
Fig. 1
Schematic depiction of different MV rescue systems available. To generate infectious MV particles, the exact full-length RNA genome or anti-genome has simultaneously to be available in a given cell together with the viral ribonucleoprotein complex proteins N, P, and L. For this purpose, the genomes were originally driven by T7 polymerase and ended with a delta ribozyme, yielding the need for co-expression of the T7 polymerase, in addition. a For this purpose, 293-3-46 rescue cells stably expressing MV-N, MV-P, and the T7 polymerase are co-transfected with the MV genome plasmid of interest, e.g., p(+)MV, and a T7 polymerase-driven expression plasmid for MV-L, e.g., pEMC.La. b As an alternative, T7-driven expression plasmids for the MV genome as well as for the other components of the RNP can be co-transfected e.g., into 293T cells, which are superinfected by a replication-deficient vaccinia vector, e.g., MVA-T7. c Finally, successful rescue has been demonstrated after co-transfection of DNA polymerase II driven expression plasmids for the MV genome as well as for the other components of the RNP complex. Hatched boxes promoter sequences; dark gray boxes termination/polyadenylation signals; white boxes individual genes

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