Recombinant Vaccine Strategies
Several genes from different etiologic agents have been cloned, expressed and purified to be tested as vaccines. There are a variety of expression systems for antigenic protein components, such as bacteria, yeast, mammalian cells and insect cells, in which the DNA encoding the antigenic determinant can be inserted and expressed. However, several factors must be taken into account before selecting the system for antigen expression. The level of expression obtained using each specific expression vector and promoter, the selection marker of choice, the presence or absence of post-translational modification by the recombinant vector, among others, are essential features that interfere in the efficacy of production of recombinant antigens as vaccines. Bacterial expression systems are the most used due to the ease of handling and to their capacity for high level expression. However, for antigens in which post-translational modifications (e.g., glycosylation) are necessary, the use of mammalian or insect cells should be considered (2, 4).
Most of the vaccines under investigation today are based on highly purified recombinant proteins or subunits of pathogens (7). The classical example of recombinant protein vaccines currently in use in humans is the vaccine against hepatitis B (5). Hepatitis B virus (HBV) infection is a chronic liver disease occurring worldwide. HBV presents a marked tropism for human liver cells, partially due to a specific receptor that is expressed on the surface of infected cells. The current vaccines are produced by expressing the hepatitis B surface antigen (HBsAg) in yeast cells. The HBsAg assembles into virus-like particles (VLPs), which are extremely immunogenic, making the HBV vaccine a very efficacious vaccine. The yeast expression system may secrete the antigen into the culture supernatant that can facilitate its purification (1,3). Furthermore, yeast cells offer some of the eukaryotic cellular machinery responsible for the post-translational modification of proteins, being capable of rendering proteins glycosylated. The technology of production of the HBV vaccine has been transferred to several manufacturers and the prices have decreased due to competition, which has rendered this vaccine affordable to most developing countries.
Licensed viral and bacterial vaccines for use in humans:
a. Live attenuated (Viral):
• Yellow Fever
b. Live attenuated (Bacterial):
• BCG (tuberculosis)
• Salmonella typhi (oral)
The development of New Vaccine Strategies
The prevention of important infectious diseases such as HIV, TB and malaria, among others, continues to be a challenge for the vaccinology field in the 21st century. Furthermore, it is most likely that vaccines for such pathogens will not become available by following the classical approaches of successful traditional vaccines. Nonetheless, considerable advances in the fields of immunology, molecular biology, recombinant DNA, microbiology, genomics, bioinformatics, and related areas have provided novel insights to help elucidate important pathogenic mechanisms involved in these infectious diseases and in pathogen interaction with the host. Altogether, these advances have led to the development of several new vaccine strategies with promising results. It seems now clear that an integrated approach will be necessary to foster continued progress in the immunology field, which probably constitutes the limiting factor for the development of new vaccines. It is also important to realize that the challenges of vaccine development are not limited to the discovery of safe and effective antigens, adjuvants and delivery systems. The balance between cost, benefits and risk should certainly be evaluated before translating a vaccine candidate to the clinic (6).
 Adkins JC, Wagstaff AJ. Recombinant hepatitis B vaccine: a review of its immunogenicity and protective efficacy against hepatitis B. BioDrugs 1998; 10: 137-158
 Clark TG, Cassidy-Hanley D. Recombinant subunit vac-cines: potentials and constraints. Dev Biol 2005; 121: 153-163.
 Dertzbaugh MT. Genetically engineered vaccines: an over-view. Plasmid 1998; 39: 100-113.
 Hansson M, Nygren PA, Stahl S. Design and production of recombinant subunit vaccines. Biotechnol Appl Biochem 2000; 32 (Part 2): 95-107.
 Michel ML, Tiollais P. Hepatitis B vaccines: protective ef-ficacy and therapeutic potential. Pathol Biol 2010; 58: 288-295.
 Nascimento IP, and Leite L.C.C. Recombinant vaccines and the development of new vaccine strategies. Brazilian Journal of Medical and Biological Research 2012; 45: 1102-1111.
 Perrie Y, Mohammed AR, Kirby DJ, McNeil SE, Bramwell VW. Vaccine adjuvant systems: enhancing the efficacy of sub-unit protein antigens. Int J Pharm 2008; 364: 272-280