A vaccination strategy incorporating DNA priming and mucosal boosting using tetanus toxin fragment C (TetC)

Intramuscular (i.m.) immunisation of BALB/c mice with a DNA vaccine, pcDNA3 /tetC. encoding fragment C (TetC) from tetanus toxin, stimulated production of TetC specific IgG2a antibodies in the serum and release of IFN-gamma fr om TetC stimulated splenocytes. A similar pattern of immune response was de tected if pcDNA3/tetC primed mice were boosted i.m. with purified TetC prot ein or TetC and cholera toxin (included as an adjuvant). In contrast. contr ol mice primed with the empty DNA vector pcDNA3 and boosted i.m. with TetC or TetC and CT. generated a dominant IgG1 specific anti-TetC response in th e sera and low or undetectable levels of IFN-gamma from stimulated splenocy tes. Thus, i.m. priming with a DNA vaccine modulated the subsequent immune response to the same antigen administered as a protein boost. Similar obser vations were made when DNA primed mice were boosted using the intranasal mu cosal route of immunisation. Interestingly, although mice immunised with pc DNA3/tetC and boosted mucosally with TetC and CT produced anti-TetC IgA in mucosal secretions. the titres were reproducibly lower than those detected in mice immunised with the pcDNA3 vector alone. The immunomodulatory effect of pcDNA3/tetC appeared to be antigen specific as mucosal boosting with an unrelated antigen (pertactin) revealed no significant modulation in terms of the anti-pertactin immune response. (C) 2001 Elsevier Science Ltd. All r ights reserved.