Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity

Nat. Med. 11: 853 - 60, 2005

Speaker : 藍保欣                        Time : 2005/11/2 13:10~ 13:50

Commentator : 黎煥耀 老師               Place : Room 601

Abstract :

Development of effective vaccines to prevent chronic diseases caused by intracellular pathogens remains a major challenge for immunologists because vaccines made with dead pathogens which elicit weak cellular immunity tend to be less effective than live vaccines. But live vaccines also carry risks, particularly among immunocompromised patients. Listeria monocytogenes (Lm), an intracellualr pathogen, has been studied for decades as a model to understand cellular immunity. The authors consider that it maybe a good strategy to develop more attenuated live vaccines that can still elicit strong cellular immunity based on Lm. In this study, the authors first modify an attenuated Lm vaccine carrying OVA epitope (Lm △actA-OVA) to create a nucleotide excision repair mutant (Lm △actA/△urvAB-OVA) which can inactivated by photochemical treatment. Then they analyze the protein synthesis, bacterial morphology, infection progress of this inactivated mutant and all results indicate that this attenuated mutant is still metabolically active. Second, by analyzing MHC class I presentation of DC in vitro, induction and activation of OVA-specific CD8⁺ T cellsin vivo, they prove that this modified vaccine carrying OVA can induce effective specific cellular immune responses against OVA. Finally, they prove that mice vaccinated with attenuated vaccine are not only resistant to wild-type Lm challenge but also resistant to viral challenge by carrying corresponding viral antigen. Further more, they also demonstrate that this modified vaccine can act as an effective cancer vaccine to decrease progression of CT-26 tumor cells in mice model. In conclusion, the authors demonstrate that killed but metabolically active microbes maybe a new vaccine paradigm for eliciting effector T-cell response and providing protective immunity.

References :

1. Brockstedt D.G., et al. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. PNAS 101:13832–37, 2004.

2. Brockstedt D.G., et al. Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity. Nat. Med 11:853-60, 2005.

3. Pamer E.G., Immune responses to Listeria monocytogenes. Nat. Rev. Immunol.. 4:812-23, 2004.