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Ann Clin Trials Vaccines Res. 2017 | Volume 1 Issue 2
Global Vaccines & Vaccination Summit & B2B
November 01-02, 2017 | Toronto, Canada
Discovery of polymeric toll-like receptor-4 (TLR-4) agonists to design a pathogen mimicking vaccine
delivery system (PMVDS)
Hemachand Tummala
South Dakota State University, USA
A
new generation of vaccine adjuvants is aimed to specifically
target pathogen recognition receptors of innate immunity,
such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs).
Polysaccharides provide an exciting new platform to interact
with the innate immune system due to their abundance in
pathogens, and their relative non-toxic properties. By integrating
the knowledge from recent advancements in immune-
signaling, material science, and drug delivery, our laboratory
had discovered a novel polysaccharide polymer-based TLR-
4 agonists; Inulin, inulin acetate (InAc) and inulin benzoate
(InBz). Hydrophobic polymers InAc and InBz were synthesized
from water-soluble inulin using acetylation and benzoylation,
respectively. The TLR-4 agonistic activity of these polymers was
established in multiple immune cells (microglials, dendritic cells,
and PBMCs) by various genetic and pharmacological approaches.
By using these immune-active polymers as biomaterials, we
have rationally engineered “Pathogen Mimicking Vaccine
Delivery System” (PMVDS) that could potentially encapsulate
multiple antigens. The uniqueness of PMVDS is that it is both
an efficient vaccine delivery system similar to nanoparticles
and a vaccine adjuvant. The polymers and PMVDS particles
were thoroughly characterized by a myriad of physicochemical
techniques. The effect of the size of the particles, dose of an
antigen and adjuvant on immune-activation was studied in
mice. The adjuvanticity of PMVDS was established in multiple
animal species (mice, pigs, sheep, and dogs), multiple routes
of administration (intradermal, subcutaneous, and nasal) and
with multiple antigens (peptides and proteins). The safety of
PMVDS was assessed using cytotoxicity, skin histochemistry
and in-vivo imaging techniques. The robustness of PMVDS
in preventing/treating the diseases was investigated on
influenza and melanoma mouse models. In conclusion, using
an interdisciplinary approach we have engineered PMVDS as
a unique platform vaccine delivery and adjuvant technology,
which will have broader applications in designing the next
generation vaccines against challenging disease where both
humoral and cell-mediated immunity is desired.
Speaker Biography
HemachandTummalahadextensivetrainingandexpertiseonformulationdevelopment
(Pharmaceutics), immunology and biochemistry. This unique combination has enabled
him to focus on interdisciplinary research to address challenges related to human and
animal health. A large emphasis of his research program is focused on discovering
functional biomaterialsthat interactwiththebiologicalsystemtoovercometherapeutic
challenges in various diseases including cancer, inflammatory diseases, and infectious
diseases (vaccines). This approach had led to the discovery of novel polymer based
TLR agonists and antagonists with applications in vaccines and inflammatory diseases,
skin penetration peptides for transdermal delivery and functional nanoformulations to
improve the pharmacokinetics of nanomedicine in cancer treatment. His discoveries
led to six patent applications and are at various stages of commercialization both in
animal and human health sectors. He also serves as a research consultant for several
small biotech and pharma industries.
e:
hemachand.tummala@sdstate.edu