MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

Effect of preexisting immunity to Salmonella on the immune response to recombinant Salmonella enterica serovar typhimurium expressing a Porphyromonas gingivalis hemagglutinin.

Recombinant Salmonella strains expressing foreign heterologous genes have been extensively studied as live oral vaccine delivery vectors. We have investigated the mucosal and systemic immune responses following oral immunization with a recombinant Salmonella enterica serovar Typhimurium expressing the hemagglutinin HagB from Porphyromonas gingivalis, a suspected etiological agent of adult periodontal disease. We have previously shown a primary mucosal and systemic response following oral immunization with chi4072/pDMD1 and recall responses following boosting at 14 weeks after primary immunization. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the Salmonella carrier strain on subsequent immune responses. Mice boosted at week 7 following immunization, a point which corresponded to the peak of the primary response, generally showed lower responses than those boosted at week 14. When mice were preimmunized with the Salmonella carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen for serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7. No reductions were seen in serum IgA or vaginal wash IgA antibodies. Mice appear to be refractory to boosting with orally administered salmonellae at 7 weeks. Deliberate immunization with the carrier strain did not appreciably affect recall responses at 14 weeks, with the exception of the serum IgG responses, nor did it affect colonization of the Peyer's patches.

Oral immunization with recombinant Salmonella typhimurium expressing a cloned Porphyromonas gingivalis hemagglutinin: effect of boosting on mucosal, systemic and immunoglobulin G subclass response.

Live avirulent Salmonella typhimurium are convenient vaccine vectors for the delivery of recombinant antigens for the induction of mucosal and systemic immunity. The hagB gene encodes a hemagglutinin of Porphyromonas gingivalis, a suspected causal agent in human adult periodontal disease. In previous studies, we have shown that hagB can be expressed in avirulent S. typhimurium and is immunogenic when given orally to mice. In this study, we evaluated recall responses in both serum and mucosal secretions after boosting. In addition, we have examined the immunoglobulin G (IgG) subclass response in serum to both HagB and the Salmonella carrier. Mice were orally immunized with S. typhimurium expressing the hagB gene and then boosted 14 weeks later. Responses were measured through 27 weeks. Both primary and recall IgG and IgA responses were seen in serum to the purified HagB as well as to the Salmonella carrier. Likewise, mucosal primary and recall responses were seen in saliva, fecal extracts and vaginal washes although the kinetics of the responses differed. The anti-HagB response in serum was dominated by IgG2a during the peak of primary response, prior to boosting and during the peak of the recall response. The anti-S. typhimurium response shifted from predominantly IgG3 following primary immunization to IgG2a after boosting. The IgG1 response was minimal against each antigen. This pattern of IgG subclass distribution is consistent with a Th1-type response. These data indicate that avirulent S. typhimurium is capable of delivering a putative virulence factor from P. gingivalis and inducing a primary and recall response in both serum and secretions and provides a means of studying P. gingivalis virulence factors and for the development of a potential vaccine.