Background We have previously reported that intramuscular, intradermal or epidermal gene gun administration of a plasmid encoding carcinoembryonic antigen (CEA) under transcriptional regulatory control of the cytomegalovirus (CMV) early promoter/enhancer elicits CEA-speci®c humoral and cellular immune responses in mice with resultant immunoprotection against challenge with syngeneic, CEA-expressing colon adenocarcinoma cells.
Methods
In the present work, we examine the ability of this DNA vaccine construct (pCEA) to elicit CEA-speci®c immunity following intrasplenic administration. Groups of mice were immunized with pCEA by intrasplenic or intramuscular injection. Six weeks later, mice were evaluated for the presence of anti-CEA humoral responses and were challenged with syngeneic, CEAexpressing colon carcinoma cells.
Results Intrasplenic administration of pCEA produced a frequency of CEA-speci®c antibody responses comparable to that elicited by intramuscular pCEA inoculation. Both intrasplenic and intramuscular administration of pCEA generated IgG2a antibody responses to CEA, consistent with the induction of T helper-1-biased immune responses. In addition, partial immunoprotection against tumor challenge was observed after a single plasmid DNA dose by either route of administration. Subsequent studies revealed that antibody responses to intrasplenic DNA vaccination are dose and schedule dependent.
Conclusion
These ®ndings support future investigations of DNA vaccination strategies that speci®cally promote the uptake of plasmid by splenocytes.