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The invention described here encompasses DNA and protein vaccines against poxviruses, and relevant immunogenic compositions, comprising at a minimum a nucleic acid encoding a modified full-length poxvirus L1R gene or its ortholog. The L1R gene is modified so that an endoplasmic reticulum-targeting sequence is operably linked on the 5′ end. Preferably the nucleic acid sequences for other poxviruses antigens are also included, such as A33R, B5R and/or A27L. These vaccines and compositions provide improved neutralizing antibody response elicited by molecular poxvirus vaccines, over known vaccines using unmodified L1R.