Single Dose of a Polyanhydride Particle-Based Vaccine Generates Potent Antigen-Specific Antitumor Immune Responses

Emad I Wafa; Sean M Geary; Kathleen A Ross; Jonathan T Goodman; Balaji Narasimhan; Aliasger K Salem

doi:10.1124/jpet.118.252809

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Single Dose of a Polyanhydride Particle-Based Vaccine Generates Potent Antigen-Specific Antitumor Immune Responses

Journal article

Open access

Peer reviewed

Single Dose of a Polyanhydride Particle-Based Vaccine Generates Potent Antigen-Specific Antitumor Immune Responses

Emad I Wafa, Sean M Geary, Kathleen A Ross, Jonathan T Goodman, Balaji Narasimhan and Aliasger K Salem

The Journal of pharmacology and experimental therapeutics, Vol.370(3), pp.855-863

09/2019

DOI: 10.1124/jpet.118.252809

PMCID: PMC6806631

PMID: 30361239

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https://doi.org/10.1124/jpet.118.252809View

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Abstract

Many factors affect vaccine efficacy. One of the most salient is the frequency and intervals of vaccine administration. In this study, we assessed the vaccine administration modality for a recently reported polyanhydride-based vaccine formulation, shown to generate antitumor activity. Polyanhydride particles encapsulating ovalbumin (OVA) were prepared using a double-emulsion technique and subcutaneously delivered to mice either as a single-dose or as prime-boost vaccine regimens in which two different time intervals between prime and boost were assessed (7 or 21 days). This was followed by measurement of cellular and humoral immune responses, and subsequent challenge of the mice with a lethal dose of E.G7-OVA cells to evaluate tumor protection. Interestingly, a single dose of the polyanhydride particle-based formulation induced sustained OVA-specific cellular immune responses just as effectively as the prime-boost regimens. In addition, mice receiving single-dose vaccine had similar levels of protection against tumor challenge compared with mice administered prime-boosts. In contrast, measurements of OVA-specific IgG antibody titers indicated that a booster dose was required to stimulate strong humoral immune responses, since it was observed that mice administered a prime-boost vaccine had significantly higher OVA-specific IgG serum titers than mice administered a single dose. These findings indicate that the requirement for a booster dose using these particles appears unnecessary for the generation of effective cellular immunity.

Animals

Cancer Vaccines - administration & dosage

Drug Compounding

Excipients

Female

Immunity, Cellular

Immunity, Humoral

Immunization, Secondary

Immunoglobulin G - analysis

Mice

Mice, Inbred C57BL

Nanoparticles

Neoplasms, Experimental - chemically induced

Neoplasms, Experimental - prevention & control

Ovalbumin - administration & dosage

Ovalbumin - immunology

Polyanhydrides

Suspensions

Details

Title: Subtitle: Single Dose of a Polyanhydride Particle-Based Vaccine Generates Potent Antigen-Specific Antitumor Immune Responses
Creators: Emad I Wafa - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (E.I.W., S.M.G., A.K.S.), University of Iowa, Iowa City, Iowa; and Department of Chemical and Biological Engineering, College of Engineering (K.A.R., J.T.G., B.N.) and Nanovaccine Institute (K.A.R., B.N., A.K.S.), Iowa State University, Ames, Iowa
Sean M Geary - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (E.I.W., S.M.G., A.K.S.), University of Iowa, Iowa City, Iowa; and Department of Chemical and Biological Engineering, College of Engineering (K.A.R., J.T.G., B.N.) and Nanovaccine Institute (K.A.R., B.N., A.K.S.), Iowa State University, Ames, Iowa
Kathleen A Ross - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (E.I.W., S.M.G., A.K.S.), University of Iowa, Iowa City, Iowa; and Department of Chemical and Biological Engineering, College of Engineering (K.A.R., J.T.G., B.N.) and Nanovaccine Institute (K.A.R., B.N., A.K.S.), Iowa State University, Ames, Iowa
Jonathan T Goodman - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (E.I.W., S.M.G., A.K.S.), University of Iowa, Iowa City, Iowa; and Department of Chemical and Biological Engineering, College of Engineering (K.A.R., J.T.G., B.N.) and Nanovaccine Institute (K.A.R., B.N., A.K.S.), Iowa State University, Ames, Iowa
Balaji Narasimhan - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (E.I.W., S.M.G., A.K.S.), University of Iowa, Iowa City, Iowa; and Department of Chemical and Biological Engineering, College of Engineering (K.A.R., J.T.G., B.N.) and Nanovaccine Institute (K.A.R., B.N., A.K.S.), Iowa State University, Ames, Iowa
Aliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (E.I.W., S.M.G., A.K.S.), University of Iowa, Iowa City, Iowa; and Department of Chemical and Biological Engineering, College of Engineering (K.A.R., J.T.G., B.N.) and Nanovaccine Institute (K.A.R., B.N., A.K.S.), Iowa State University, Ames, Iowa aliasger-salem@uiowa.edu
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.370(3), pp.855-863
DOI: 10.1124/jpet.118.252809
PMID: 30361239
PMCID: PMC6806631
NLM abbreviation: J Pharmacol Exp Ther
ISSN: 0022-3565
eISSN: 1521-0103
Grant note: P30 ES005605 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS U01 CA213862 / NCI NIH HHS
Language: English
Date published: 09/2019
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9984216711202771

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