Targeted Phage Display-based Pulmonary Vaccination in Mice and Non-human Primates.

TitleTargeted Phage Display-based Pulmonary Vaccination in Mice and Non-human Primates.
Publication TypeJournal Article
Year of Publication2021
AuthorsStaquicini DI, E Barbu M, Zemans RL, Dray BK, Staquicini FI, Dogra P, Cardo-Vila M, Miranti CK, Baze WB, Villa LL, Kalil J, Sharma G, Prossnitz ER, Wang Z, Cristini V, Sidman RL, Berman AR, Panettieri RA, Tuder RM, Pasqualini R, Arap W
JournalMed (N Y)
Date Published2021 Mar 12
KeywordsAnimals, Bacteriophages, Carrier Proteins, Ligands, Lung, Mice, Primates, United States, Vaccination

BACKGROUND: The extensive alveolar capillary network of the lungs is an attractive route for administration of several agents. One key functional attribute is the rapid onset of systemic action due to the absence of first-pass metabolism.

METHODS: Here we applied a combinatorial approach for ligand-directed pulmonary delivery as a unique route for systemic targeting in vaccination.

FINDINGS: We screened a phage display random peptide library to select, identify, and validate a ligand (CAKSMGDIVC) that specifically targets and is internalized through its receptor, α3β1 integrin, on the surface of cells lining the lung airways and alveoli and mediates CAKSMGDIVC-displaying phage binding and systemic delivery without compromising lung homeostasis. As a proof-of-concept, we show that the pulmonary delivery of targeted CAKSMGDIVC-displaying phage particles in mice and non-human primates elicit a systemic and specific humoral response.

CONCLUSIONS: This broad methodology blueprint represents a robust and versatile platform tool enabling new ligand-receptor discovery with many potential translational applications.

FUNDING: Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), research awards from the Gillson Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.

Alternate JournalMed (N Y)
PubMed ID33870243
PubMed Central IDPMC8049167
Grant ListP20 GM121176 / GM / NIGMS NIH HHS / United States
R01 CA163890 / CA / NCI NIH HHS / United States
R01 CA226537 / CA / NCI NIH HHS / United States
R01 HL131608 / HL / NHLBI NIH HHS / United States
Faculty Reference: 
Marina Cardo Vila, PhD