Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2016 Jul 20

PMID 27434590

Citations 13

Authors

Laure Lambricht

Kevin Vanvarenberg

Ans De Beuckelaer

Lien Van Hoecke

Johan Grooten

Bernard Ucakar

Pascale Lipnik

Niek N Sanders

Stefan Lienenklaus

Veronique Preat

Gaelle Vandermeulen

Affiliations

Soon will be listed here.

Abstract

DNA vaccination holds great promise for the prevention and treatment of cancer and infectious diseases. However, the clinical ability of DNA vaccines is still controversial due to the limited immune response initially observed in humans. We hypothesized that electroporation of a plasmid encoding the HIV-1 Gag viral capsid protein would enhance cancer DNA vaccine potency. DNA electroporation used to deliver plasmids in vivo, induced type I interferons, thereby supporting the activation of innate immunity. The coadministration of ovalbumin (OVA) and HIV-1 Gag encoding plasmids modulated the adaptive immune response. This strategy favored antigen-specific Th1 immunity, delayed B16F10-OVA tumor growth and improved mouse survival in both prophylactic and therapeutic vaccination approaches. Similarly, a prophylactic DNA immunization against the melanoma-associated antigen gp100 was enhanced by the codelivery of the HIV-1 Gag plasmid. The adjuvant effect was not driven by the formation of HIV-1 Gag virus-like particles. This work highlights the ability of both electroporation and the HIV-1 Gag plasmid to stimulate innate immunity for enhancing cancer DNA vaccine immunogenicity and demonstrates interesting tracks for the design of new translational genetic adjuvants to overcome the current limitations of DNA vaccines in humans.

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References

Jin X, Morgan C, Yu X, DeRosa S, Tomaras G, Montefiori D . Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015; 33(20):2347-53. PMC: 4433533. DOI: 10.1016/j.vaccine.2015.03.036. View

Ohlschlager P, Spies E, Alvarez G, Quetting M, Groettrup M . The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA. Int J Cancer. 2010; 128(2):473-81. DOI: 10.1002/ijc.25344. View

Chiarella P, Massi E, De Robertis M, Sibilio A, Parrella P, Fazio V . Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration. Expert Opin Biol Ther. 2008; 8(11):1645-57. DOI: 10.1517/14712598.8.11.1645. View

Vandermeulen G, Uyttenhove C, De Plaen E, Van den Eynde B, Preat V . Intramuscular electroporation of a P1A-encoding plasmid vaccine delays P815 mastocytoma growth. Bioelectrochemistry. 2013; 100:112-8. DOI: 10.1016/j.bioelechem.2013.11.002. View

Henrick B, Yao X, Rosenthal K . HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation. Front Immunol. 2015; 6:426. PMC: 4541371. DOI: 10.3389/fimmu.2015.00426. View

Kidd P . Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003; 8(3):223-46. View

De Geest B, Willart M, Lambrecht B, Pollard C, Vervaet C, Remon J . Surface-engineered polyelectrolyte multilayer capsules: synthetic vaccines mimicking microbial structure and function. Angew Chem Int Ed Engl. 2012; 51(16):3862-6. DOI: 10.1002/anie.201200048. View

Clark R, Kupper T . Old meets new: the interaction between innate and adaptive immunity. J Invest Dermatol. 2005; 125(4):629-37. DOI: 10.1111/j.0022-202X.2005.23856.x. View

Garinot M, Fievez V, Pourcelle V, Stoffelbach F, des Rieux A, Plapied L . PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release. 2007; 120(3):195-204. DOI: 10.1016/j.jconrel.2007.04.021. View

10.

Paul S, Piontkivska H . Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs. BMC Microbiol. 2010; 10:212. PMC: 2924856. DOI: 10.1186/1471-2180-10-212. View

11.

Babiuk S, Baca-Estrada M, Foldvari M, Storms M, Rabussay D, Widera G . Electroporation improves the efficacy of DNA vaccines in large animals. Vaccine. 2002; 20(27-28):3399-3408. DOI: 10.1016/s0264-410x(02)00269-4. View

12.

Scheerlinck J . Genetic adjuvants for DNA vaccines. Vaccine. 2001; 19(17-19):2647-56. DOI: 10.1016/s0264-410x(00)00495-3. View

13.

Bachmann M, Jennings G . Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol. 2010; 10(11):787-96. DOI: 10.1038/nri2868. View

14.

Flingai S, Czerwonko M, Goodman J, Kudchodkar S, Muthumani K, Weiner D . Synthetic DNA vaccines: improved vaccine potency by electroporation and co-delivered genetic adjuvants. Front Immunol. 2013; 4:354. PMC: 3816528. DOI: 10.3389/fimmu.2013.00354. View

15.

Kalams S, Parker S, Jin X, Elizaga M, Metch B, Wang M . Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults. PLoS One. 2012; 7(1):e29231. PMC: 3252307. DOI: 10.1371/journal.pone.0029231. View

16.

Grunwald T, Ulbert S . Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases. Clin Exp Vaccine Res. 2015; 4(1):1-10. PMC: 4313101. DOI: 10.7774/cevr.2015.4.1.1. View

17.

Manel N, Hogstad B, Wang Y, Levy D, Unutmaz D, Littman D . A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature. 2010; 467(7312):214-7. PMC: 3051279. DOI: 10.1038/nature09337. View

18.

Silva J, Zupancic E, Vandermeulen G, Oliveira V, Salgado A, Videira M . In vivo delivery of peptides and Toll-like receptor ligands by mannose-functionalized polymeric nanoparticles induces prophylactic and therapeutic anti-tumor immune responses in a melanoma model. J Control Release. 2014; 198:91-103. DOI: 10.1016/j.jconrel.2014.11.033. View

19.

Kobiyama K, Jounai N, Aoshi T, Tozuka M, Takeshita F, Coban C . Innate Immune Signaling by, and Genetic Adjuvants for DNA Vaccination. Vaccines (Basel). 2015; 1(3):278-92. PMC: 4494227. DOI: 10.3390/vaccines1030278. View

20.

Donnelly J, Wahren B, Liu M . DNA vaccines: progress and challenges. J Immunol. 2005; 175(2):633-9. DOI: 10.4049/jimmunol.175.2.633. View