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is a potential means of inserting elements without the use of a selectable marker,
since several rare restriction sites (required for linearisation of the BAC prior to
recombination) are absent from the MVA genome. For pre-clinical work, an in
vitro site specific recombination system could be developed [72].
The vaccine vector capability of Vaccinia virus expressing a recombinant anti-
gen was demonstrated nearly 25 years ago [73], [74]. Successful vectored vaccines
for diseases such as malaria, HIV-AIDS and tuberculosis will likely require combi-
nations of antigens and delivery systems able to induce immune responses of the
right character and magnitude against the recombinant antigens. Currently, MVA
is one of the more promising deployable delivery systems and has potential for
improvement. The MVA-BAC technology provides an opportunity to accelerate
production of candidate vaccines for evaluation, and potentially a superior start-
ing point for clinical vaccine manufacture.
Acknowledgements
We thank Arban Domi and Bernard Moss for plasmids; Richard Wade-Martins
and Michele Lufino for advice and help, Jeremy Robertson for synthesis of IβT β T
and Søren Warming for recombineering materials and advice.
Author contributions
Conceived and designed the experiments: SG MC AS. Performed the experi-
ments: MC JF SS AS RA. Analyzed the data: MC AS. Wrote the paper: MC.
Other: Principal Investigator: AH.
references
1. Mayr A, Stickl H, Muller HK, Danner K, Singer H (1978) [The smallpox vac-
cination strain MVA: marker, genetic structure, experience gained with the par-
enteral vaccination and behavior in organisms with a debilitated defence mecha-
nism (author's transl)]. Zentralbl Bakteriol [B] 167: 375-390.
2. Drexler I, Heller K, Wahren B, Erfle V, Sutter G (1998) Highly attenuated
modified vaccinia virus Ankara replicates in baby hamster kidney cells, a po-
tential host for virus propagation, but not in various human transformed and
primary cells. J Gen Virol 79 (Pt 2): 347-352.
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