Oral transgene vaccination mediated by attenuated Salmonellae is an effective method to prevent Herpes simplex virus-2a induced disease in mice

An attenuated strain of Salmonella typhimurium has been used as a carrier f or oral genetic immunization. The eukaryotic expression vector pCMV contain ing the gene of the glycoprotein D (gD) Of the herpes simplex virus 2 was u sed to transform Salmonellae. The oral immunization with the transformed sa lmonellae elicited a strong cellular immune response in both, the mucosal a nd systemic compartments (spleen, ileal lymph nodes and Peyer patches). The immune response mainly consisted in a dramatic activation of IFN-gamma -se creting cells. Twenty hours following the challenge with five lethal doses of virus, mRNA for IFN-gamma was observed in vaginal tissues from mice immu nized with salmonella harboring the plasmid pgD but not in tissues from mic e immunized by the intramuscular route with pgD. After an intravaginal chal lenge all immunized mice survived without developing symptoms. Furthermore, the immunization with Salmonella resulted in a more effective control of v iral shedding than intramuscular immunization. We have unequivocally demons trated by the introduction of an intron in the green fluorescent protein th at the expression of the plasmid was due to the transcription of the protei n by an eukaryotic nuclear process and not as a result of expression of the protein by the bacteria. Macrophages and dendritic cells were found expres sing the protein in systemic and mucosal compartments of the immune system. (C) 2001 Elsevier Science Ltd. All rights reserved.