Infectious diseases are one of the biggest burdens on global health; killing at least 10 million people annually. The easiest and perhaps also most effective way to manage infectious diseases is through vaccination. A vaccine is defined as any foreign substance or preparation that on administration produces active protection against disease. The eventual goal of a vaccine is to induce immunity and immunological memory similar to natural infection but without actually causing the disease.

The first vaccine was produced by Edward Jenner in 1798 for smallpox, derived from cowpox virus. It was a simple preparation of pus from a cowpox blister that was inoculated. Since then, research and development (R&D) in the field of vaccinology has progressed immensely.

Although R&D has taken new vaccines to the cutting edge of technology, vaccines currently in use are still based on the basic and traditional principles of immunization.

Classical vaccine technology
There are several vaccines, currently in use, that are produced using “older” or classical technology. New technology is being explored in order to make some of these vaccines more efficient, with fewer side effects and more cost effective. Classical vaccine technology includes:
● Killed/inactivated: these are previously virulent micro-organisms, which have been killed with chemicals or heat.
● Attenuated: micro-organisms that have been cultivated under conditions that disable their virulent properties, or which use closely related but less dangerous organisms to produce a broad immune response.
● Toxoid: these are inactivated toxic compounds in cases where these (rather than the micro-organism itself) cause illness.
● Subunit: rather than introducing an inactivated or attenuated micro-organism to an immune system, a fragment of it can create an immune response.
● Conjugate: certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen.

Old vaccine technology:
● Grow in animals (vaccinia in calves for smallpox; rabbit brains for rabies)
● Simple bacterial culture (Cholera vibrio) then inactivation
● Grow in eggs (influenza, vaccinia) then inactivate

Experimental and latest vaccine technology
Novel research is aimed at the preparation of more effective vaccines. Technology has enabled scientists to experiment with vaccines that are more targeted in their mode of action or have a greater probability of eliciting immune responses required for protection against a disease. Increased knowledge of genetics and the latest recombinant DNA technology has made room for specialization in the field of vaccinology. Research on an HIV/AIDS vaccine has been the motivation for many of the novel vaccine technologies!

Recombinant DNA technology
Research attempts to make vaccines that are more effective, cheaper, and safer. A variety of recombinant DNA techniques can be used to make improved vaccines.
● Recombinant pathogen (attenuated) vaccines: producing a recombinant pathogen that is modified such that its virulence is reduced, while preserving its antigenicity.
● Recombinant proteins/ peptide vaccines: recombination technology to produce proteins/peptides (in bacteria or yeast) that on administration serve as antigens.
● Recombinant vector vaccines: genes for antigens from pathogen are transferred to a viral vector (such as Vaccinia virus, Adenovirus, Poxvirus) that is not infective or less infective than pathogen.
● Plasmid vaccines (DNA Vaccines): genes for antigens from pathogen are transferred to a plasmid vector that is administered directly (using a “gene gun”).

Other approaches
Scientists have also been toying with various other approaches for development of novel vaccines. These approaches are not only limited to actual immunogenic agents but also to other vaccine components, vaccine delivery systems and routes of administration.

Multivalent Subunit Vaccine: Synthetic peptides that represent immunodominant T or B-cell epitopes are being evaluated as vaccines for several diseases. This approach enables immunologists to produce defined vaccines that may permit selective activation of humoral or cell mediated branches of immune system. Multivalent Subunit Vaccines include the use of solid matrix-antibody antigen, Micelles, Liposomes and Immunostimulating complexes (ISCOMS).

Anti-idiotype vaccines: comprise antibodies that have three-dimensional immunogenic regions, designated idiotopes that consist of protein sequences that bind to cell receptors. Idiotopes are aggregated into idiotypes specific of their target antigen. When these anti-idiotype antibodies are administered, they mimic the antigen and elicit an immune response.

Virus like particles (VLPs): consist of proteins that form a virus' outer shell and the surface proteins, without the nucleic acids required for replication. In some cases these proteins are embedded within a lipid bilayer and are also known as virosomes. VLPs used as vaccines are often very effective at eliciting both T cell and B cell immune responses.

Novel adjuvants: Adjuvants are pharmacological or immunological agents that modify the effect of other agents (e.g., drugs, vaccines) while having few if any direct effects when given by themselves. They are often included in vaccines to enhance the recipient's immune response to a supplied antigen while keeping the injected foreign material at a minimum. Novel adjuvants currently in research include Cytokines, Saponins, Liposomes and even Bacterial Products

Novel delivery systems/ routes of administration: For decades, children and adults alike have been vaccinated with the use of needles and syringes, barring a few oral vaccines. The anxiety of getting pricked has often been a deterrent in taking vaccines. New research has also focused on novel delivery systems such as nasal sprays (e.g., FluMist against Influenza), edible vaccines that are often incorporated into fruits such as apples or bananas and even mouth strips (like breath strips) that melt on the tongue!

Conclusion
Traditional research in vaccinology has mainly targeted infectious agents for the better half of the 20th century. Innovative research being done in more recent times has broadened our focus and allowed us to consider other conditions such as cancer and Alzheimer’s disease in the list of being protected through vaccination.

Safer, cheaper and more effective vaccines that are easier to administer has been the objective of latest R&D. However, it is also as important to focus on neglected diseases and to ensure that everyone, especially those from resource-limited settings, have access to the existing vaccines.

-The author is Scientific Officer,
Dept. of Virology, Haffkine Institute, Mumbai