Polymers as synthetic immune stimulatory molecules in vaccine delivery
Over
the previous
couple of decades, vaccine delivery has evolved
substantially, shifting from the utilization of conventional inactive or live
attenuated pathogen to more advanced recombinant substances with adjuvants (the
boosting agents that enhance immune stimulation). Polymers as adjuvants have
augmented the formulation and delivery of vaccines, resulting in modern
vaccination approaches through oral and nasal pathways. the utilization of
polymeric substances in vaccines is gaining popularity, primarily due to their
ability to
enhance vaccine efficacy and achieve desired immune
responses through targeted delivery. Diverse approaches for vaccine delivery
that are currently available are listed in Table 1.
Table 1: Different vaccine delivery techniques
|
Technique |
Example |
|
Adjuvant |
Poly lactic co-Glycolic Acid (PLGA),
Alum, Liposome |
|
Oral vaccine |
Enteric-coated formulation |
|
DNA vaccine delivery |
Gene gun |
|
Intranasal |
Bio-adhesive polymer |
|
Topical |
Patches of vaccine |
Inoculating
live attenuated pathogens has benefits like long-lasting immunity thanks to low
virulence induced mild infection with signs of a uniform pathogen of the
target. However, a severe disadvantage of this method is that the risk related to severe
infection thanks
to the probability of the attenuated pathogen mutating into
a more virulent strain. Although safer than an attenuated vaccine, inoculation
of inactive pathogens may have disastrous results if not inactivated
properly. a
serious man-made polio epidemic broke call at 1955 within the US
when defectively inactivated polio vaccines were administered to 200,000
children. It had caused 40,000 cases of polio, killing ten and leaving over 200
paralysed.
Despite a high production rate, poor safety and
production error incidents have necessitated advanced approaches to vaccine
delivery. One such approach is that the development of recent , robust
vaccines that use ‘adjuvants’ to elicit a fast and effective immune reaction .
Adjuvants tend to
make complexes with delivery agents resulting in a
slow release of the immunogens. These adjuvants contain the conserved molecular
signatures of the pathogens that help stimulate immunity thanks to recognition
by receptors (e.g. pattern recognition molecules like “Toll-like receptor”)
located on the B-cells and dendritic cells of the cells mammals in unmethylated
CpG islands. Vaccines are often delivered in various forms like
microparticles, emulsions and immune-stimulatory complexes or liposomes. Ramon
first described the utilization of adjuvants in vaccine delivery
around 100 years ago. Since then, gradual improvements are made
for more potential output.
Primary purposes of using adjuvants are:
(a) Decrease in number of doses and quantity of antigen
(b) Increase within the speed and duration of immuno-response
(c) Induction of strong cell-mediated and mucosal immunity
Based on biodegradability, polymeric substances
are divided into two categories; natural (gelatin, chitosan, dextran, agarose,
alginate) and
artificial . The polymeric nanoparticles (0.1µm – 10 µm
sized colloids made from natural or synthetic polymers) are suitable as
vaccine delivery agents thanks to their preferable size and capability for
releasing and protecting antigens by enzymatic degradation within the gastrointestinal tract.
The nanoparticles are taken up quickly by mucosa-associated lymphoid tissue or
MALT. samples
of such nanoparticles include poly alkyl cyanoacrylate (or
PACA), poly methyl-methacrylate (or PMMA). Sometimes the nanoparticles are
labelled with monoclonal antibodies (a sort of antibody prepared
by cloning the white blood cells within the laboratory) for
specific M-cells to reinforce the absorption and elicit an immune reaction .
Ellagic acid (an essential natural bioactive molecule for cancer treatment),
when formulated with nanoparticle PCL [poly (ε-caprolactone)], showed increased
bioavailability. The bioavailability of DAUN or daunorubicin through the oral
pathway was reported to extend by 10-folds as chitosan coating was
applied along
side nanoparticle DAUN-PLGA.
The use of Poly (lactic-co-glycolic acid) (PLGA)
for the delivery of matrix antigen has been recognised recently thanks to its
rapid uptake by M-cells and transportation to lymphatic tissues. Linear
polysaccharide chitosan, a partial deacylated sort of chitin,
serves the
aim of a mucoadhesive. Since it’s charged , it binds easily
with immunogenic DNA (negatively charged) and is usually preferred over
PLGA.
Table 2: Successful vaccine delivery systems
using polymers
|
Antigen |
Polymer |
Route of delivery |
|
Diptheria toxoid |
Poly (lactic-co-glycolic acid) or
PLGA |
Intramuscular |
|
Tetanus toxoid |
Poly (lactic acid) or PLA and PLGA |
Subcutaneous |
|
B. pertussis hemagluttin |
Poly (lactic-co-glycolic acid) or
PLGA |
Intranasal |
|
Influenza virus, formalinized |
Poly (lactic-co-glycolic acid) or
PLGA |
Peroral and subcutaneous |
Polymers
are mainly used as vaccine carriers and adjuvants by encapsulating the antigen
particles for the controlled release of vaccines inside the body. Polymeric
substances in vaccines are used efficiently against several diseases. the utilization of
natural or synthetic-borne biocompatible polymers has opened new avenues
for the
event of recent vaccines.
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