Recombinant bacterial vaccines
Highlights
► The advantages and disadvantages of recombinant bacterial vaccines are discussed with relevant examples. ► Recombinant subunit vaccines are safer but have a demanding manufacturing process. ► Recombinant whole cell vaccines demonstrate better immunogenicity but represent a regulatory challenge due the safety concerns. ► Recombinant bacterial carriers are being developed for delivery of vaccines toward infectious as well as metabolic diseases. ► New approaches like structural vaccinology are key in vaccine design against antigens that are highly variable.
Introduction
Vaccines for infectious diseases have come a long way, starting from the Jenner's cowpox vaccines two centuries ago to the present day vaccines designed using recent technologies like reverse and structural vaccinology. The field of vaccinology, primarily founded on Pasteur's principles has yielded several effective vaccines. In fact, today, the vast majority of licensed vaccines are live attenuated or killed/inactivated microorganisms [1]. However, given that there are still several deadly diseases that lack an efficient vaccine, it is becoming pertinent to apply newer technologies to quicken the search for better and safer vaccines [2]. The advent of genetic engineering has given scientists the ability to rationally design both individual microbial components as well as whole organisms. Furthermore, the application of functional genomics and structural biology has allowed the identification of many promising new antigens. Although at present there are few licensed vaccines that are based on recombinant technology, it is quite clear that novel genetic technologies have a crucial role to fulfill in the years to come. The aim of this review is to illustrate the use of recombinant DNA technology in bacterial vaccine development using examples of existing and future vaccines.
Section snippets
Recombinant subunit vaccines
The main drivers for recombinant protein-based vaccine development are developing less reactogenic, more potent, safer, better characterized vaccines, in addition to developing vaccines that provide broader protection against multiple serotypes/serogroups of a bacterium. The first of these vaccines was the highly pure surface antigen of the hepatitis B virus expressed in yeast [3]. The second, a Bordetella pertussis subunit vaccine (acellular vaccine) containing three highly pure proteins
Recombinant bacterial strains
Whole cell vaccines are a common vaccine strategy for many diseases, especially when the immune responses involved are complex. Historically, many attenuated vaccine strains like Bacille Calmette Guerin (BCG) and Salmonella typhi Ty21a were generated by continuous passage or chemical mutagenesis [20]. With recombinant technology, pathogens can now be manipulated to generate non virulent, but immunogenic strains. Targeted attenuated mutants of various human pathogens have shown promise in animal
Vaccines based on protein structure
Structural vaccinology, a recent approach based on the use of information derived from protein structure and epitope mapping can be used in the rational design of new recombinant vaccines, particularly against antigens characterized by a complex antigenic variability. This approach has been applied to design fully synthetic proteins to induce multivalent protection. Cell surface pili, protective antigens of GBS, exist as six immunogenically different but structurally similar variants. Based on
Conclusions
Recombinant DNA technology has indeed changed the face of vaccinology by enabling rational design vaccines against complex human diseases (Figure 1). Despite excellent evidence of success of recombinant vaccines in pre-clinical and clinical studies, few recombinant vaccines are licensed for human use. This can however be attributed to the intense regulatory processes revolving around recombinant vaccine production. Improved adjuvant technologies, new approaches like systems biology and advanced
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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