Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential?

Abstract

Safety-tested modified vaccinia virus Ankara (MVA) has been established as a potent vector system for the development of candidate recombinant vaccines. The versatility of the vector system was recently demonstrated by the rapid production of experimental MVA vaccines for immunization against severe acute respiratory syndrome associated coronavirus. Promising results were also obtained in the delivery of Epstein-Barr virus or human cytomegalovirus antigens and from the clinical testing of MVA vectors for vaccination against immunodeficiency virus, papilloma virus, Plasmodium falciparum or melanoma. Moreover, MVA is considered to be a prime candidate vaccine for safer protection against orthopoxvirus infections. Thus, vector development to challenge dilemmas in vaccinology or immunization against poxvirus bio-threat seems possible, yet the right choice should be made for a most beneficial use.

Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies

“…MVA has been identified as a safe and immunogenic carrier of foreign antigens and have in many applications become a vector of choice for recombinant vaccine development [25] and [26]. Critically, the recombinant MVA failed to elicit any detectable humoral responses upon oral administration of high doses and afforded no protection in our murine model.…”

“…MVA has been identified as a vaccine vector of choice in many recent and ongoing vaccine development studies [25] and [26]. Additionally, MVA was used as a smallpox vaccine towards the end of the smallpox eradication effort and therefore has an established safety record for use in humans.…”

“…MVA virus has been proven to be phenotypically and genotypically stable and although the virus fails to productively infect most mammalian cell lines tested (including cells of human origin), recombinant genes are still efficiently expressed in non-permissive cells [34], [35], [36] and [37]. MVA delivers antigens in a highly immunogenic way to stimulate both cellular and humoral responses [38] and its efficacy as a vaccine vector has been evaluated in a myriad of infectious disease and tumor models [26], [39], [40] and [41].…”

Vaccine properties of a novel marker gene-free recombinant modified vaccinia Ankara expressing immunodominant CMV antigens pp65 and IE1

“…Analysis of the MVA genome revealed six major deletions [41]. Deletions II and III were developed and widely used for insertion of foreign genes to create recombinant MVA (rMVA) via homologous recombination [36,42]. To isolate rMVA from parental wt MVA, several screening methods were developed, including color development by metabolism of substrates by bacterial marker genes such as β-galactosidase or β-glucuronidase [43].…”

“…The direct repeat (DR) sequence from pLW51 used to construct pZWIIA is derived from 149058 to 149298 of the MVA genome. pZWIIA has four essential components: 1) Sequence flanking Del II of MVA corresponding to genome position 20718 to 21284 for FL1 and 19972 to 20666 for FL2, originally incorporated into pLW22 [36]. 2) An expression cassette, which includes two vaccinia synthetic promoters (Psyn I from pLW22 and Psyn II from pLW51) arranged head to head to independently promote foreign insert gene expression.…”