“Recombinant vaccines: Applications and Challenges”
Sajida Jamshaid *
Department of Genetics, Virtual University, Pakistan
A vaccine is a biological preparation which increase the immunity to a particular disease. A vaccine mainly contains an agent that resembles a disease causing microorganisms and is often made from weakened or killed forms of the microbes. This agent stimulates the body immune system to recognize the agent as foreign that destroy it, and keep a record of it so that the immune system can more easily recognize and destroy any of these microorganisms.
The use of recombinant proteins allows the targeting of immune responses focused against protective antigens. There are a variety of expression systems with different advantages that allows the production of large quantities of proteins depending on the required characteristics.
Key words: vaccine, immunity, recombinant protein and immune responses.
Vaccines were initially developed on empirical basis. By advancement in the field of Immunology, Molecular biology, Biochemistry, Genomics, and Proteomics have been added new perspectives to the field of vaccinology. 2
Vaccines do not guarantee complete protection from a disease. This is due to a lowered immunity in general because the host’s immune system does not have a B-cell capable of generating antibodies to that antigen. Due to which the infection will be less severe and heal faster than before. 1
Types of vaccines:
There are various types of vaccines are as follows:-
1. Killed (inactivated) vaccines
2. Attenuated vaccines
3. Toxoid vaccines
4. Subunit vaccines
5. Conjugate vaccines
6. Experimental vaccines
7. Valence vaccines
1. Killed Vaccines:
Killed Vaccines are prepared when safe live vaccines are not available. Some vaccines contain killed, but virulent microorganisms that have been destroyed with chemicals, heat, radioactivity or antibiotics. Examples of these are the influenza vaccine, cholera, bubonic plague vaccine, polio vaccine, hepatitis A vaccine, etc. 1
Attenuated vaccines are viral in nature but some are bacterial. Examples include the viral diseases yellow fever, measles, rubella, and mumps & bacterial disease typhoid etc. The live Mycobacterium tuberculosis vaccine is not made up of a contagious strain but contains a virulently modified strain called BCG that used to create an immune response to the vaccine. 1
Toxoid vaccines are made up from inactivated toxic compounds that causes illness rather than the microorganism i.e. tetanus & diphtheria. 1
Protein subunits rather than introducing an inactivated or attenuated microorganism to an immune system. Examples include the subunit vaccine against Hepatitis B virus that is composed of only the surface proteins of the virus the virus like particle, vaccine against human papilloma virus that is composed of the viral major protein. 1
Various bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins the immune system can be led to recognize the polysaccharide as if these were protein antigens. 1
These are monovalent or multivalent. A monovalent vaccine is that designed to immunize against a single antigen or single microorganism. A multivalent vaccine is designed to immunize against two or more strains of them same microorganism or against two or more microorganisms. 1
A few of viral vectors that have been investigated for the application as the vaccine antigen carriers. We use here replicating or non replicating viruses as a platform to deliver vaccine antigen. The major challenge is the induction of vector specific immunity against the antigen to infect or kill the target tumor cells. However this problem can be eradicated by adopting best immunization strategies i.e. the use of viruses that do not circulate in humans and use of different viruses for prime immunizations. 3
It have been studied for their potential usage in gene therapy. Here the use of linear double stranded DNA virus takes place as a vector for vaccine delivery. Adenoviruses have become most important vectors for vaccine development. Vast advantages of using these viruses as a vaccine platform include their ability to infect a broad range of hosts and to induce high levels of transgene expression without the potential of viral genes being integrated into the host genome. 3
Genetically engineered viruses:
Genetically engineered viruses are being increasingly used as live vaccine vectors and their applications may have environmental implications that must be taken into account in risk assessment and management processes. In most legislative frameworks that are treated as genetically modified organisms are require environmental risk assessment in addition to the evaluation of the quality, safety and efficacy of the product before clinical trial applications are submitted. The ERA is performed in order to identify the potential risks for public health and the environment that may arise due to the use. If risks are identified and considered as not acceptable this process should go on to propose appropriate risk management strategies capable to reduce these risks. 6
Applications of Genetically modified viruses:
There are four broad GMV applications that have environmental implications are as follow:
i. Immunization against infectious diseases in different livestock species.
ii. Immunization of wild life species which are infectious agents causing disease in humans and other organisms.
iii. Control of pest animal population by direct lethal control operations.
iv. Human vaccination programs against infectious diseases such as cancers. 8
Recombinant vaccine strategies:
Millions of children worldwide die from infectious diseases, despite currently available vaccines. Thus, social, political and economic policies are not less important issues and cannot be overlooked. 2
There are a variety of expression systems in which the DNA encoding the antigenic determinant can be inserted and expressed. 2
Bacterial expression systems are the most used due to ease of handling and for high level expression. However for antigens in which Post translational modifications are very essential the use of mammalian or insect cells should be considered. 2
Transgenic plants are used to produce recombinant pharmaceutical proteins.
Recombinant proteins i.e. vaccines and antibodies can be produced in plants by applying two systems are as follow:
Stable genetic transformation and transient expression. Stable transformation is included of integrating a gene into the plant nuclear/chloroplast genome. The use of biopharming technology to produce vaccines in plants to overcome major problems of traditional vaccines. This technology eliminate dangerous effects of contamination with animal pathogens and provide a very cheaper, useful & safer alternative method. 4 6
Vaccines and Autism:
Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. A worldwide increase in the rate of autism diagnose driven by the broadened diagnostic criteria and increased awareness has been concerns that an environmental exposure might cause autism. Theories for this putative association have centered on the measles mumps rubella vaccine and the large number of vaccines currently administered. However both these studies epidemiological and biological have been fail to support these claims. 5
Avian infectious bronchitis is an economically important poultry disease that affects the respiratory, renal, and reproductive systems of chickens. Although it was first identified in North Dakota USA, epidemiological evidences confirmed the circulation of several IBV serotypes in different parts of the world. 14
Some doubts regarding vaccination
1. Why all vaccines 100% effective
2. Why are there so many Vaccines?
3. Is natural immunity better than vaccine acquired Immunity?
4. Why do some vaccines require booster
5. Can Babies immune systems handle so many vaccines?
6. Is the polio vaccine linked to HIV?
7. Why is there a new flu vaccine every year?
A larger number of vaccine products are currently on the market and these are being taken up by more recipients. Despite this in countries where income is low over a third of deaths occur in children which is the cause of infectious disease. This is the importance of overcoming the complex issues. A report from the Pharmaceutical Research and Manufacturers of America listed 145 new vaccines undergoing clinical trials testing with the many targeting infections for which there is no current vaccine. The scientific, financial and ethical challenges are considerably important breakthroughs continue to be made. 9
It is also important to realize that the challenges of vaccine development are not limited to the discovery of safe and effective antigens for the adjuvants and delivery systems. The balance between cost its benefits and risk should certainly be evaluated before translating a vaccine to the clinic. 2
There are now a number of examples that unwanted characteristics of poxvirus vectors can be modified or excluded by targeted mutagenesis, homologous recombination and reverse genetics. But the safety benefits of these approaches can only be taken out when we have clarified putative GMV characteristics and adverse effect issues within the categories known unknowns and unknown unknowns. 7 8
1 D.K. Sanghi, Rakesh Tiwle, A DETAIL COMPREHENSIVE REVIEW ON VACCINES International Journal of Research and Development in Pharmacy and Life Sciences February to March, 2014, Vol. 3, No.2, pp 887-895.
Sanghi D.K., Tiwle R., A review on “A detail comprehensive review on vaccines”, Int. J. Res. Dev. Pharm. L. Sci., 2014, 3(2), pp.887-895.
2 I.P. Nascimento and L.C.C. Leite, Recombinant vaccines and the development of new vaccine Strategies, Braz J Med Biol Res, December 2012, Volume 45(12) 1102-1111 doi: 10.1590/S0100-879X2012007500142
3 Youngjoo Choi, Viral vectors for vaccine applications, Clin Exp Vaccine Res 2013;2:97-105
http://dx.doi.org/10.7774/cevr.2013.2.2.97 pISSN 2287-3651, eISSN 2287-366X
4 Samaneh Bagheri and Barat Ali Fakheri, Plants as factories for the Production of Pharmaceutical recombinant proteins, Bull. Env. Pharmacol. Life Sci., Vol 3 8 July 2014: 149-155 ©2014 Academy for Environment and Life Sciences, India, Online ISSN 2277-1808.
5 Jeffrey S. Gerber and Paul A. Offit, Vaccines and Autism: A Tale of Shifting Hypotheses, Clinical Infectious Diseases 2009; 48:456–61. 2009 by the Infectious Diseases Society of America.
6 Anne Ingeborg Myhr and Terje Traavik, Genetically Engineered Virus-Vectored Vaccines – Environmental Risk Assessment and Management Challenges,
7 Louz, D., Bergmans, H. E., Loos, B. P. & Hoeben, R. C. (2005). Cross-species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live-virus vaccines. The Journal of Gene Medicine, Vol. 7, pp. 1263- 1274.
8 Weli, S. C. & Tryland, M. (2011). Avipoxviruses: infection biology and their use as vaccine vectors. Virology Journal, Vol. 8, pp. 49.
9 Petra Oyston and Karen Robinson, The current challenges for vaccine development, Journal of Medical Microbiology (2012), 61, 889–894 DOI 10.1099/jmm.0.039180-0
10 He, Y., Xiang, Z. & Mobley, H. L. (2010). Vaxign: the first web-based vaccine design program for reverse vaccinology and applications for vaccine development. J Biomed Biotechnol 2010, 297505.
11 Baz Morelli, A., Becher, D., Koernig, S., Silva, A., Drane, D. & Maraskovsky, E. (2012). ISCOMATRIX: a novel adjuvant for use in prophylactic and therapeutic vaccines against infectious diseases. J Med Microbiol 61, 935–943.
13 McElligott, S. (2009). Addressing supply side barriers to introduction of new vaccines to the developing world. Am J Law Med 35, 415–441.
14 Faruku Bande, Siti Suri Arshad, Mohd Hair Bejo, Progress and Challenges toward the Development of Vaccines against Avian Infectious Bronchitis, Hindawi Publishing Corporation Journal of Immunology Research Volume 2015, Article ID 424860, 12 pages http://dx.doi.org/10.1155/2015/424860.
15 Sala, F., Rigano, M.M., Barbante, A., Basso, B., Walmsley, A.M. & Castiglione, S. (2003). Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives. Vaccine., 21: 803-808.
16 Bakker, H., Bardor, M., Molthoff, J.W., Gomord, V., Elbers, I., Stevens, L.H., Jordi, W., Lommen, A., Faye, L., Lerouge, P., Bosch, D. (2011). Galactose-extended glycans of antibodies produced by transgenic plants. Proc Natl Acad Sci USA., 98:2899–2904.
17 Sandstrom E, Nilsson C, Hejdeman B, et al. Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara. J Infect Dis 2008;198:1482-90.
18 Colmenero P, Liljestrom P, Jondal M. Induction of P815 tumor immunity by recombinant Semliki Forest virus expressing the P1A gene. Gene Ther 1999;6:1728-33.
19 Ni B, Gao W, Zhu B, et al. Induction of specific human primary immune responses to a Semliki Forest virus-based tumor vaccine in a Trimera mouse model. Cancer Immunol Immunother 2005;54:489-98.
20 Kim JW, Gulley JL. Poxviral vectors for cancer immunotherapy. Expert Opin Biol Ther 2012;12:463-78.