Research ArticlesNanomedicine

Generation of Effector Memory T Cell–Based Mucosal and Systemic Immunity with Pulmonary Nanoparticle Vaccination

Science Translational Medicine  25 Sep 2013:
Vol. 5, Issue 204, pp. 204ra130
DOI: 10.1126/scitranslmed.3006516

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Nanoparticle Vaccine Delivered to Lungs

Delivering vaccines to the lungs has been shown to protect against not only respiratory infections but also pathogens that enter in other organs, including the gastrointestinal and reproductive tracts. To capitalize on this phenomenon, Li and colleagues designed a pulmonary vaccination strategy that uses nanoparticle carriers to deliver antigen and adjuvant to the mucosal surface lining the lungs.

Nanosized particles called interbilayer-crosslinked multilamellar vesicles (ICMVs) were engineered to contain antigen along with two Toll-like receptor agonists, which served as adjuvants to stimulate airway epithelial cells and promote dendritic cell uptake and cross-presentation. Mice that received ICMVs containing the model antigen ovalbumin (OVA) showed a greater T cell response than did those that received soluble OVA vaccine, with more OVA-specific T cells in the lungs after 11 weeks. ICMV-based vaccines were next put to the test in therapeutic tumor and prophylactic viral challenge models. As a therapeutic vaccine, all mice that received OVA-ICMVs after an injection of OVA-expressing melanoma cells resisted tumor formation and had prolonged survival. In the challenge model, animals were first given ICMV vaccines loaded with the peptide antigen AL11 [from simian immunodeficiency virus (SIV) gag], then exposed to vaccinia virus expressing SIV gag. Only animals that received pulmonary vaccination—not subcutaneous or soluble vaccine—were protected from viral challenge, showing a reduction of viral titers in the lungs and other organs.

The nanoparticle vaccine demonstrated systemic protection when delivered locally to the lung mucosa. The authors suggest that ICMV vaccines stimulated the generation of a large population of effector memory T cells in the lungs and circulation, thus conferring such high protection in mice. Although the ICMVs were determined to be safe and well tolerated in small animals, additional safety and efficacy studies will be needed in larger animals before translation.