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Leishmanization like first-generation and third-generation vaccines that use genetically modified Leishmania parasites or use bacteria and viruses that carry Leishmania genes is daunted by the issue of standardization [ 34 ]. Human studies have to be commended despite raised points of standardization and licensure purposes.
First-generation vaccines are less costly and easy to manufacture. In addition, first-generation vaccines are the only human prophylactic VL vaccines that went on to phase III.
Khalil and colleagues conducted the first human phase III VL vaccine study that was followed by a number of extended phase II studies on vaccines against visceral leishmaniasis [ 27 ]. Lack of funds under the pretense of poor standardization and lack of licensure potentials prevented progression of alum-precipitated Leishmania vaccines to phase III [ 22 , 23 , 24 , 25 , 35 , 36 , 37 ]. The future of VL control is bleak based on frequent VL pandemics that kill thousands of people in developing countries, increasing drug resistance, lack of new antileishmanial drugs in the pipeline, and failure of second-generation vaccines to make it to phase III.
Strategies for designing and optimizing new generation vaccines
Important points have to be highlighted when revisiting first-generation vaccines: the Vaccinia [smallpox] vacine which is the first vaccine that helped to eradicate small pox has been a whole virus. Furthermore, the control and near elimination of poliomyelitis is successful due to the blessing of an attenuated whole virus.
Since the above vaccines are considered fit for human use, whole parasite vaccines have to be given a similar standing especially in the era of existing strong adjuvants. Furthermore, the success of immunochemotherapy of post-kala-azar dermal leishmaniasis using alum-precipitated autoclaved L.
The inconclusive results that were obtained from first-generation vaccine meta-analysis and put it into disrepute are probably due to the fact that the analysis included studies for cutaneous as well as visceral diseases in the same basket. It has to be clearly stated that these disease phenotypes are different with different immune responses and different endpoints of evaluation of efficacy [ 12 , 13 , 23 , 25 , 27 , 35 , 36 , 38 , 39 , 40 , 41 ]. Safety and immunogenicity have been assured in phase I and II studies. But, it is clear that strong adjuvants are needed for these subunit vaccines to be satisfactorily immunogenic.
It was concluded that these peptides can be taken further for prophylactic leishmanin vaccine development. Further studies are underway to combine these peptides with known and potential adjuvants to increase their immunogenicity [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. In conclusion, second-generation VL vaccines will succeed when the mechanisms by which macrophages select the most suitable epitopes to induce the appropriate immune response are known. DNA vaccines came into existence with advances in molecular biology and biotechnology, and the injection of small circle of DNA encoding potentially immunogenic proteins became a reality [ 50 ].
A number of experimental third-generation vaccines have been studied with demonstrated immunogenicity and healing abilities. The vaccine was shown to be safe and immunogenic [ 51 , 52 , 53 ]. A plethora of adjuvants, live organisms BCG , cytokines, oligonucleotide CpG , minerals and particulate lipids, and polymer-based adjuvants are under investigations for Leishmania vaccine. Although there is an urgent need for studies on adjuvants in disease-endemic areas, access to potent adjuvants is the main hurdle for investigators and researchers in leishmaniasis-endemic countries [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].
Failure of second- and third-generation vaccines to reach phase III, rising drug resistance, and continued devastating VL pandemics make it a necessity to study further first-generation vaccines. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers.
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