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Microbiology: Current Research 2017
Volume 1 Issue 2
Microbes Infection 2017
Notes:
Page 40
September 28-29, 2017 | London, UK
Microbes Infection
38
th
Annual congress on
BIOMATERIALS THAT ENGINEER INFECTION
IMMUNITY
James D Bryers
University of Washington, USA
G
ene-based nucleic acid vaccines are capable of eliciting
protective immunity in humans to persistent pathogens,
e.g., HIV, malaria, and tuberculosis, for which conventional
protein/peptide vaccines have failed. Recent identification
and characterization of genes coding for tumor antigens has
stimulated the development of nucleic acid-based cancer
vaccines. With increasing life expectancy in high-income
countries and newly emerging infections in low-income
countries, new technologies are required to address changing
vaccine needs. Nucleic acid vaccines have the potential to
address these needs, but despite decades of research there
is still no commercial product for human use. Nucleic acid
vaccines (pDNA, mRNA) have certain advantages over protein
antigen vaccines: (a) they lack theMHC haplotype restrictions
of peptide/protein antigens and (b) nucleic acid vaccines are
not subject to neutralization by the host immune response,
thus allowing repeat boosting. Messenger RNA (mRNA) is
a promising alternative to plasmid DNA (pDNA) since (a)
mRNA does not require nuclear entry for activity, (b) mRNA
does not integrate into the host genome, and (c) mRNA does
not require cancer derived promoters (e.g., CMV). However,
to be commercially competitive as a platform technology,
mRNAbased vaccines must match the potency of viral vectors
at doses of RNA that are not cost prohibitive. Our work seeks
to maximize mRNA vaccine efficacy by (a) enhancing vaccine
delivery route, (b) developing an autocatalytic, self-replicating
mRNA (SRmRNA) vector, and (c) magnifying dendritic cell
(DC) antigen uptake and activation using chemokine therapy.
We could carry out this entire immunization study using
the classic model antigen, ovalbumin (OVA) (as the protein
or its gene). However, the strong CD8+T cell responses
elicited against the highly immunogenic OVA peptide
may not be indicative of responses to more native epitopes
from pathogens or tumor antigens. Consequently, here we
will focus on preventing bacterial infections of implanted
medical devices. This project has developed a scaffold-
based vaccine technology, superior to mucosal or systemic
delivery. Implants release mRNA vaccines (or pDNA for
comparison) that transfect arriving antigen-presenting cells
(specifically dendritic cells - DCs) to produce T- and B-cell
memory and antibody expression against the select pathogen,
and potentially stimulate direct native killer T-cell responses
(ideal for intracellular infecting bacteria).
jbryers@uw.eduMicrobiology: Current Research 2017