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Virology Research Journal
Volume 1 Issue 4 Vaccines World 2017
Notes:
Page 23
November 09-10, 2017 Vienna, Austria
21st World Congress and Exhibition on
VACCINES, VACCINATION & IMMUNIZATION
Harnessing the immunogenicity of viral proteins for
designing novel cancer DNA vaccines
Gaëlle Vandermeulen, Laure Lambricht and Véronique Préat
Louvain Drug Research Institute - University of Louvain, Belgium
Harnessing the power of the immune system to destroy
or prevent cancers is a highly attractive strategy and a
unique approach to cancer therapy. Competitive advantages of
cancer vaccines are exquisite specificity, low toxicity, and the
potential for a durable treatment effect due to immunologic
memory, but their development is challenging due to the low
immunogenicity of tumor antigens. As it is the case for cancer,
a proper activation of cytotoxic T cells is necessary to clear
infection by killing virus-infected cells. For that purpose, the
immune system is able to detect and eliminate certain viral
threats. We aim to investigate if the expression of specific
viral proteins could similarly promote cancer immunization.
DNA vaccine is a simple, versatile and clinically applicable
method that could greatly benefit from such a strategy. We
first demonstrated that the co-administration of a plasmid
encoding the HIV-1 Gag viral capsid protein enhanced
the efficacy of melanoma DNA vaccine. It 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. Safety and immunogenicity of
pGag have been demonstrated in human in the context of
HIV vaccine development. Its use as a genetic adjuvant is thus
of particular interest from a translational point of view. We
then engineered the vesicular stomatitis virus G glycoprotein
as permissive insertion sites allowed T-epitope insertions.
Inclusion of either ovalbumin MHC class I or MHC class II
restricted epitopes induced the proliferation of specific CD8+
and CD4+ T cells, respectively. The cytotoxic T-cell response
was high when the two plasmids were co-delivered allowing
a protective therapeutic effect against B16F10-OVA tumor.
In conclusion, Gag and VSV-G proteins can be exploited for
designing DNA vaccine strategies with promising therapeutic
potential in cancer.
Recent Publications
• Lambricht L, Vanvarenberg K, De Beuckelaer A, Van
Hoecke L, Grooten J et. al. (2016) Co-administration of
a plasmid encoding HIV-1 Gag enhances the efficacy of
cancer DNA vaccines. Molecular Therapy. 24(9):1686-
1696.
• LambrichtL,LopesA,KosS,SersaG,PréatV,Vandermeulen
G (2016) Clinical potential of electroporation for gene
therapy and DNA vaccine delivery. Expert Opinion on
Drug Delivery. 13(2):295-310.
• Vandermeulen G, Vanvarenberg K, De Beuckelaer A, De
Koker S, Lambricht L et. al. (2015)The site of administration
influences both the type and the magnitude of the immune
response induced by DNA vaccine electroporation.
Vaccine. 33(28):3179-3185.
• Vandermeulen G, Uyttenhove C, De Plaen E, Van den
Eynde B, Préat V (2014) Intramuscular electroporation of a
P1A-encoding plasmid vaccine delays P815 mastocytoma
growth. Bioelectrochemistry.100:112-118.
• Vandermeulen G, Athanasopoulos T, Trundley A, Foster K,
Préat V, Yáñez Muñoz R J, Dickson G (2012) Highly potent
delivery method of gp160 envelope vaccine combining
lentivirus-like particles and DNA electrotransfer. Journal
of Controlled Release. 159(3):376-83
Biography
Gaëlle Vandermeulen is a senior Postdoctoral Researcher at the University
of Louvain. After completing a Master's degree in Pharmacy, she joined
the Advanced Drug Delivery and Biomaterials group at the Louvain Drug
Research Institute of the University of Louvain (UCL). Her PhD work was part
of a European project and she spent several months at the Université Paris
Descartes. She completed a PhD on skin DNA electroporation in 2008 and
performed a Postdoctoral stay focused on HIV DNA vaccine at the Royal
Holloway University of London. She aims to develop novel delivery systems for
nucleic acid-based drugs, with a particular focus on DNA vaccines.
Gaëlle Vandermeulen, Virol Res J 2017, 1:4