Dataset Information

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

ABSTRACT:

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 in vivo 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.

SUBMITTER: Staquicini DI

PROVIDER: S-EPMC8049167 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundClaims of non-live vaccines having deleterious effects on non-targeted infectious disease and mortality among females persists. The majority of the available evidence is from West Africa and consists of observational studies and the interpretation and implications are controversial. Results from high-income countries have been conflicting. We evaluated the association between a human papillomavirus vaccine, a non-live vaccine primarily administered to pre-adolescent females, and non-targeted infectious disease in a high-income country.MethodsWe constructed a nationwide cohort of all Danish females 10 to 29 years of age during 2007 to 2016 with information on quadrivalent human papillomavirus vaccination status and infectious disease hospital contacts using national registers. Nested in this cohort, we conducted a self-controlled case series (SCCS) analysis comparing the rates of hospitalisation in a 90-day main risk period following the latest vaccination to reference period rates with adjustment for age and season.FindingsWe included 853,879 Danish-born females aged 10 to 29 years of age during the 2007 to 2016 study period in the study cohort. We identified a total of 65,293 infectious disease hospitalisations among 50,599 participants; 46,955 cases among 37,003 participants vaccinated during follow-up were included in the SCCS analysis. There was no statistically significantly increased risk of infectious disease hospitalisation in the 90-day main risk period (rate ratio 0.92, 95% CI 0.88 to 0.95).InterpretationReassuringly, our large well-controlled study does not support that human papillomavirus vaccination increases the risk of non-targeted infectious disease in any clinically meaningful way. While our study does not provide evidence against adverse effects of other non-live vaccines, it does provide evidence against the claim that all non-live vaccines increase risk of heterologous infections in females.FundingThe study was supported by the Novo Nordisk Foundation.