Introduction
A vaccine is apreparation that is used to stimulate the body’s immune response against diseases. The platform is defined as a vehicle used for a particular purpose or to carry a usually specified type of equipment. Vaccine platform technologies use a platform base carrier, such as a nucleic acid, or viral vector, which can be modularised with target antigenic components of pathogens. In all these ways of producing vaccines, one has a basic manufacturing process that does not change the so-called “platform”. That is, the way mRNA, DNA – plasmids, viral vectors, etc. are made does not change. It is consistent and always works the same way. However, the genetic code for the desired antigen can be exchanged.
The followings are the common modern vaccines platform-
- Recombinant vector
- mRNA
- DNA
Types of Modern Platform Vaccines
1.Recombinant-Vector Vaccine
Genes that encode major antigens of especially virulent pathogens can be introduced into attenuated viruses or bacteria. The attenuated organism serves as a vector, replicating within the host and expressing the gene product of the pathogen.
Vectors: Vectors are the agents that carry selected genes that encode foreign antigens. Genetically engineered vectors can either be used as vaccines themselves or used to produce large amounts of antigens in vitro that can then be incorporated into vaccines. Vectors include bacteria, DNA viruses, yeasts, plasmids, and even plants. Several organisms have been used for vector vaccines, including vaccinia virus, the canarypox virus, attenuated poliovirus, adenoviruses, attenuated strains of Salmonella, BCG strain of Mycobacterium bovis, and certain strains of Streptococcus that normally exist in the oral cavity. Adenovirus is the most well-studied viral vector.Some important vectors are:
a. Poxvirus Vectors
Poxviruses are the most widely used vectors in vaccines because they have a very large genomethat can accommodate large inserts. For example, mammalian poxviruses such as vaccinia have a 190 kb genome, whereas fowlpox and canarypox have genomes of more than 300 kb. As a result, a 10 kb base-pair segment of the vaccinia genome can be removed and up to 30,000 base pairs of foreign DNA can be inserted without affecting virus infectivity. Multiple foreign genes can therefore be inserted into a single vector. By splicing genes from selected pathogens into a poxvirus vector and using this as a vaccine, we can immunize recipients against all these pathogens. Unlike other DNA viruses, poxviruses have their transcription machinery, RNA polymerase, and post-transcriptional modifying enzymes so this permits self-sufficient replication in the cytoplasm of infected cells. They can express high levels of the new antigen. The poxviruses are also easy to administer by dermal scratching or by ingestion.
b. Adenovirus Vectors
Adenoviruses are a large family of double-stranded DNA viruses that cause respiratory and gastrointestinal diseases in humans and animals. They elicit strong cell-mediated and antibody-mediated immune responses. They have a wide host range and infect multiple cell types. They can be delivered by injection and orally. The most commonly used vector is human adenovirus-5. The adenovirus genome is a linear chain consisting of 36 kb of DNA.
Why Adenovirus Vector Vaccines?
Adenovirus genome is well characterized and easy to manipulate. It has a tropism for both dividing and non-dividing cells. It can grow in high titer in tissue culture. It may be administered systemically and through a mucosal route. It is thermostable, so it is easy to store. Able to express large quantities of foreign antigens. It Stimulates both systemic and mucosal immunity.
Advantages of recombinant vector vaccine
They allow the simultaneous expression of multiple antigenic determinants and also avoid the hazards of whole pathogenic viruses, maximizing their safety. The ability of vectored vaccines to infect cells and so express endogenous antigens ensures that they are very efficient at inducing both antibody- and strong T cell-mediated responses. They do not require complex purification. These vaccines are safe, they cannot be transmitted by arthropods, and they are not excreted in body fluids.
2. RNA Vaccine
Messenger RNA is produced by the transcription of DNA and translated into proteins. Thus when it enters cells it triggers protein expression. This mRNA is only transiently expressed, and as a result, is potentially safer than persistent DNA. RNA can be synthesized so that it incorporates open reading frames that encode proteins combined with sequences at both termini that regulate translation and protein expression. The Pfizer-BioNTech and Moderna COVID-19 vaccines are messenger RNA vaccines.
Non-Replicating and Self Replicating RNA Vaccine
RNA can be delivered to cells in two forms, conventional mRNA or self-amplifying mRNAs also called replicons. Replicons are defined as nucleic acids that contain the instructions for their replication. Both types of RNA are safe and well-tolerated and induce antigen-specific immune responses. However, most of the infectious disease focus has been on self-amplifying vectors—replicons, derived from alphaviruses because these are highly effective and require a much lower dose of RNA to induce a protective immune response.
Advantages
They stimulate cellular, as well as humoral immunity. mRNA vaccines have the production advantage that they can be designed swiftly. Moderna designed their mRNA-1273 vaccine for COVID-19 in 2 days. RNA synthesis is relatively simple. It can be readily produced by a standardized process reducing both cost and time. Only information about the RNA sequence is required and there is no need to handle dangerous pathogens. They are cheaper and faster to produce.
Disadvantages
Storage: Because mRNA is fragile, some vaccines must be kept at very low temperatures to avoid degrading, thus giving the recipient little effective immunity.
Side effects: Reactogenicity is similar to that of conventional, non-RNA vaccines. However, those susceptible to an autoimmune response may have an adverse reaction to mRNA vaccines.
3.DNA Vaccine
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response. When a DNA plasmid enters a cell nucleus in a recipient animal, it will be transcribed into mRNA. The mRNA is transported to the cell cytoplasm and translated into protein. The recipient cells will therefore synthesize and express the foreign antigen. As with virus-encoded proteins, this endogenous antigen will be processed, bound to MHC class I molecules, and expressed on the cell surface.
Delivery of DNA Vaccine
I. Gene gun
Plasmid entry into cells can also be achieved by “shooting” the DNA plasmids directly through the skin adsorbed onto microscopic gold or tungsten nanoparticles. These are fired by a “gene gun” (Fig. 1) using compressed helium. This will allow rapid delivery of a vaccine to large populations without the requirement for huge supplies of needles and syringes.
Fig. 1
II. Electroporation
Electroporation is another way to overcome the problems associated with getting DNA plasmids inside cells. This combines an intramuscular injection with the local application of a pulsed electric field of 50 to 1000 v through needle electrodes for a few micro- or milliseconds. After this electrical pulse, the muscle cell membranes become temporarily permeable and open pores that allow the plasmids to enter the cell (Fig. 2).
Fig. 2
III. Mucosal surface delivery
It is usually doneusing cationic liposome-DNA preparations, and biodegradable microspheres.
Advantages
DNA vaccines are very safe & have persistent responses. Presented by both MHC class I and II molecules. Relatively easy and cheap to produce. It doesn’t require adjuvants. It is very specific for an antigen-coded protein. It induces both humoral and cell-mediated immunity. Refrigeration is not required for the handling and storage of the plasmid DNA. There is no risk of infection.it is stable for storage and shipping.
Disadvantages
It is Limited to protein immunogens (not useful for non-protein-based antigens such as bacterial polysaccharides). There may be chances of cross-contamination when manufacturing different types of live vaccines in the same facility.
Conclusion
Outbreaks of H1N1 influenza, Middle East Respiratory Syndrome, Ebola, COVID-19, and Zika over the last decade, are timely reminders that improved modern vaccine technology is necessary to shorten the developmental and production time of vaccines. Vaccine platform technologies, the formulation of antigens of choice with a pre-defined platform base, have the potential to address vaccine manufacturing challenges such as speed, safety, and efficacy. Once designed and licensed for one vaccine, the development of future vaccines using the same platform should simply require the substitution of the desired antigenic component, enabling faster and cheaper development, regulatory approval, and mass production.