Polymers as synthetic immune stimulatory molecules in vaccine delivery

Over the last few decades, vaccine delivery has evolved substantially, shifting from the use 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, leading to modern vaccination approaches through oral and nasal pathways. The use of polymeric substances in vaccines is gaining popularity, primarily because of their ability to improve vaccine efficacy and achieve desired immune responses through targeted delivery. Diverse approaches for vaccine delivery that are currently available have been 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 due to low virulence induced mild infection with signs of an identical pathogen of the target. However, a severe disadvantage of this method is the risk associated with severe infection due 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 major man-made polio epidemic broke out in 1955 in 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 the development of modern, robust vaccines that use ‘adjuvants’ to elicit a quick and effective immune response. Adjuvants tend to form complexes with delivery agents leading to a slow release of the immunogens. These adjuvants contain the conserved molecular signatures of the pathogens that help stimulate immunity due 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 can be delivered in various forms like microparticles, emulsions and immune-stimulatory complexes or liposomes. Ramon first described the use of adjuvants in vaccine delivery around 100 years ago. Since then, gradual improvements have been made for more potential output.  

Primary purposes of using adjuvants are: 

(a) Decrease in number of doses and quantity of antigen 

(b) Increase in the speed and duration of immuno-response 

(c) Induction of robust cell-mediated and mucosal immunity 

Based on biodegradability, polymeric substances are divided into two categories; natural (gelatin, chitosan, dextran, agarose, alginate) and synthetic. The polymeric nanoparticles (0.1µm – 10 µm sized colloids made up of natural or synthetic polymers) are suitable as vaccine delivery agents due to their preferable size and capability for releasing and protecting antigens by enzymatic degradation in the gastrointestinal tract. The nanoparticles are taken up quickly by mucosa-associated lymphoid tissue or MALT. Examples of such nanoparticles include poly alkyl cyanoacrylate (or PACA), poly methyl-methacrylate (or PMMA). Sometimes the nanoparticles are labelled with monoclonal antibodies (a type of antibody prepared by cloning the white blood cells in the laboratory) for specific M-cells to enhance the absorption and elicit an immune response. 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 increase by 10-folds as chitosan coating was applied along with nanoparticle DAUN-PLGA. 

The use of Poly (lactic-co-glycolic acid) (PLGA) for the delivery of matrix antigen has been recognised recently due to its rapid uptake by M-cells and transportation to lymphatic tissues. Linear polysaccharide chitosan, a partial deacylated form of chitin, serves the purpose of a mucoadhesive. Since it’s positively charged, it binds easily with immunogenic DNA (negatively charged) and is sometimes 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 have been used efficiently against several diseases. The use of natural or synthetic-borne biocompatible polymers has opened new avenues for the development of modern vaccines. 



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