The significant advancements in the genomic regime have shifted the focus of therapeutic developments and vaccination to sequence-based approaches from a microbiological orientation. It has been observed that the genome sequences offer the research to identify the mechanism of pathogenesis working. For the purpose of designing new vaccination and drugs and their effect on the patient’s health with the prescribed issues, immunomics, proteomics, structural genomics, metabolomics, transcriptomics, and genomics. With changing environmental lapses and conditions, numerous new diseases have taken over the major death toll in health statistics and demands for developing new vaccines through advanced drug designs help patients to resist the growing infections among human patients. Thus, for controlling emerging infectious diseases in the future new genome-based approaches and genomic data will help in developing new vaccines which are expected to be result oriented within lesser time.
Keywords: Genome, Vaccination, Genome Sequences, Pathogenesis, Drug Design
Infectious diseases have a history of taking over human health since the beginning. However, the introduction and usage of vaccination for preventing and controlling the spread of the disease has controlled these infectious diseases and saved many lives. The genomic era has been a blessing for human health, however, it shall be notified as well that all the newly designed vaccinations even though the advanced drug design is first attempted on animals and how they react towards this disease.
Though there have been numerous advancements in this field, even then classic pathogens like measles and typhoid who have been affecting human health around the world have been studied and captivated through the identification of the actual virus-like hepatitis C virus and Helicobacter pylori). It has been observed as well that the diseases in the past have re-emerged like Dengue and Group A streptococcus. These infections have developed immunity against the previous medications and the genomics field has to conduct a detailed study for knowing the cause of the improvement of immunity of these bacterial cells against the vaccination and at what rapid rate they are growing and need to be countered (Moxon, 2002).
The World Health Organisation has reported fact that the changing environmental conditions have increased the chances of the introduction of a new infection every year. Moreover, these pathogens break in the form of epidemics. Thus, for limiting the spread and causing any major damage to the human population, the introduction of these vaccinations on time is the only effective solution with the guarantee of 100% effectiveness (Mutoloki, Cooper, Marjara, Koop & Evensen, 2010). The traditional empirical approaches for the development of vaccines while screening a few candidates are time-consuming and have not been proven to be result oriented for every disease. Such as the HIV virus cannot be contained in a laboratory and the HCV virus cannot experiment with through suitable animal models for identifying the degree of infection and its treatment. These viruses are observed to be controlled by the T cell-dependent immune responses instead of humoral immune responses. Genomics is expected to be the first respondent in case of any pathogen attack and will help in immediate functional characterization, diagnostic development, and antigen identification (Ling, Ban, Wen, Wang & Ge, 2013).
The first ever genomic sequence was developed for ‘Haemophilus influenza’ in 1995, the finished bacterial genomic sequence has helped and assisted the sequencing technology to take the lead and further improve on the set grounds. For each major human pathogen disease, at least one genomic sequence is available which can be studied and certain improvisations can help in the earlier control of the epidemic.
Fig-1: Genome-based approaches for Controlling EIDs (Izzo & Schneider, 2010)
The statistics of 2009 for the World Health Organization report that almost 1000 bacterial genomes have been completed in refined forms and are ready to be used and over 3000 viral genomes are under observation and study to be launched for the development of a vaccine to control any future epidemic. Any bacterial pathogen has more than 4000 genes that need to be structured and evaluated for designing any vaccination. Once the entire sequence is identified only when the potential candidates could be short-listed for experimentation. On the other hand, viral pathogens have as few as 10 genes which are not only convenient to be sequenced anytime sooner but could be tested on any potential candidate for the restoration of the health issue.
Construction of recombination of genes
Pathogen Genome Sequencing
Cloning of Gene of interest
Figure 2: Vaccine Developmental Stages
Hence, the identification of host genomes and pathogens can help in the accurate targeting of drug targets and vaccinations. Thus, it has increased the chances of identifying the possible pathogen in individuals than using conventional methods. The genome-based projects have helped in a better understanding of protein functions, pathogenesis, epidemiology, and microbial physiology (Jeanguenin et al., 2011).
The Pili identification in terms of long filamentous structures extending from the bacterial surface and the basic streptococci pathogenic strains is a better example for understanding and conducting the research on the right platform for discovering the genomic sequence for the protein functions. The virulent factors and behaviors are best described in the pile of gram-negative bacteria. However, little information was available on the pili in gram-positive bacteria before the detailed analysis of S. pneumoniae, S. agalactiae, and S. pyogenes (Spier, 2014).
While analyzing the S. agalactiae genome sequences, among them three protective antigens were highlighted through pan-genomic reverse vaccinology (Niu & Liang, 2008). These antigens contain the LPXTG motifs and these typical proteins with the cell wall anchoring were observed to be combining with the pili. The bioinformatics analysis showed that the exposed antigen surfaces elicited protected immunity among mice when injected with these pathogens. Thus, the limited variability of S. agalactiae pili, it has been observed that the different combinations used for the three pilin subunits could lead to broader protective immunity among the suspected patients (Ogholikhan & Schwarz, 2016).
However, the complete genomic sequence of S. pneumoniae and the advanced information available for the pilus proteins in the pathogenic streptococci helped in discovering two pilus islands encoding proteins playing adherence to colonization in a murine model of infection and lung epithelial cells. These proteins are considered to be eliciting inflammatory responses among the host. The presence of the protective agent in the pili. Although, there have been seen relative similarities between human infectious diseases and animal-based infectious diseases in pathogenesis it shall be definitely and explicitly acknowledged that the vaccination development for both types of health issues in different species are developed independently despite the similarities.
Thus, various factors have been identified for differentiating the vaccination even with the same symptoms such as targeted outcomes after vaccination, types of animals to be vaccinated, economic benefits of vaccinations, and catering to the actual cost of the vaccination. Moreover, the vaccination developed for the industrial animals is specially designed keeping in view the benefits like increasing the number of live stocks and their presence from any infectious disease which could be hazardous for consumption in humans. Another purpose is that the animals cannot be exposed to chemotherapy as it will affect the quality of meat and the toxins will be affecting the health of the consumers of their meat (Hogue & Ling, 1999).
There are different types of vaccinations developed for animals such as increasing and protecting the meat of livestock meat, preventing the spread of disease to other animals, or preventing them from generating infectious viruses which are hazardous to human health. The non-therapeutic use of antibiotics may increase the risk of developing immunity against the pathogens in livestock and could be transferred as a residue to meat consumers, especially humans. Thus, the usage of vaccines can help in eliminating the development of such immunity (Sette & Rappuoli, 2010). However, for this purpose, the vaccines are to be improved over the course of time so that they are advanced and effective against pathogens. Due to these reasons, the use of antibiotics in animals has been strictly restricted in Australia and Europe. Recently advanced measures have been taken for establishing similar steps in the USA and other advanced countries’ live stocks.
The vaccinations are produced by several different patterns such as the production of a virus-like particle without specific genetic materials, insertion of a required gene into a carrier to be delivered or expressed, alteration of host-specificity for the pathogen, use of immunogenic components alone, and inactivation or attenuation of the pathogen. Moreover, Apart from the benefits of developing vaccines for human-related diseases only, it has been observed that numerous of infections identified over the years have been passed on from animals to humans (Ogholikhan & Schwarz, 2016). Therefore, it was required that apart from designing the genomic sequence of drugs as per human needs, the vaccines shall be looking into treating the infections in animals first so that they are restricted to their hosts and are not transferred to humans through any type of contact.
The highlighted advantage of this process is that conducting the research is of lower cost in comparison to a human vaccine. In addition, the vaccines developed for animals require fewer clinical trials and complexities which are mostly expected in human trials. Thus, the animal vaccine prepared is ready to be launched in lesser time than the human vaccine and since many infections are transferred due to different species of animals it is not hard to stay that such infections could be contained without reaching out to the human population and the expected damage to occur on a larger scale will be controlled within no time (Mutoloki, Cooper, Marjara, Koop & Evensen, 2010).
The demand for increasing the production of the animal vaccines has grown over the past decade due to the emerging pathogens in the livestock industry (Sette & Rappuoli, 2010). However, it does not limit the effectiveness of the vaccine and demands that any vaccine developed shall comply with all the safety rules and shall be result oriented rather than damaging animal health. There is indeed a novel concept for developing new vaccines due to the availability of a great deal of genomic information on various pathogens and advanced molecular techniques.
Viral Vaccines for Animals
For controlling any type of infectious disease, the development and implementation of viral diseases is the most appropriate option the reason that antibiotic drugs have been analyzed to be ineffective for controlling the virus rather have turned out to be the source of transferring the suspected virus to any person or animal coming in contact with the virus carrier. The majority of the vaccinations are produced by veterinary companies for secure livestock production and other industrial animals (Castiblanco & Anaya, 2015). Even the World health organization has been working on introducing vaccination for preserving wildlife from the outbreak of viruses in the wild due to pollution and sudden climatic changes. For this purpose, the vaccines for controlling the virus are produced by adding necessary proteins to the cell structure, chicken embryos, live animals, and tissues.
Effective Responders to Vaccination
Thus, it has been clarified from the above-stated research so far that the animal genome is different from the human genome no matter if they are interrelated through similarities or their origin. Due to this animal genomics specifically focuses on the individual response of each animal towards any vaccination due to their different genetic traits (“Synthetic Genomics boosts RNA vaccines”, 2017). Due to serious efforts and recording of results, several disparities have been recorded in the clinical trial of animals towards any new vaccination, the Veterinarians involved in these clinical trials have been characterizing these changes in the response of animals as the animal challenges models. Thus, it has raised the need for robust regulatory standards like improved laboratory practices and sound biometric analyses (de Barsy & Greub, 2013). It will help in avoiding any type of environmental and experimental biases in animal clinical trials. Thus, this attempt will help in the effective profiling of the vaccines and is expected to offer better improvisations in the vaccines for the eradication of the spread of infectious diseases among animals.
The recent issue of the OIE Scientific and Technical Review stated the fact that the majority of the immunogenetics studies have been focusing on poultry species and livestock for resisting the disease. It has been observed through few specific studies available that the immunological responses of an individual animal’s genotype predetermine limited responses to vaccinations (Ling, Ban, Wen, Wang & Ge, 2013). A study by Newman et al stated the differences in the large half-sibling families with the infused antibody responses of B. abortus Strain 19, which is known as a live attenuated bacterial vaccine with immediate effect when inoculated (Travis, 1999). The parametric statistical model was used for studying the incorporation of the effects of the bovine major histocompatibility complex and the parameters of related drugs (Kussell, 2005).
The study helped in identifying the individual animals’ and families’ responses toward the antibody production phenotypes thus helping in identifying the variation in the genetic structures of the experimented group of animals (Lee & Quan, 2016). While studying these traits the traits were correlated with the bulls with individual responses suggesting individual BoLA types and the existence of side effects (Yuk & Jo, 2014). It was reported by Elizabeth Glass teaching at the Roslin institute in the United Kingdom that the FMDV-specific T-cell and the BoLA haplotypes are close interrelated. In cattle population which is fully genotyped has 186 microsatellite markers and is derived from the cross between two cattle with extreme variations in their genes (Ling, Pelosi & Walmsley, 2010). Thus, variations were observed in the responses like completely non-responding to a higher degree of response. Among all the immune responses significant responses or effects were seen for the IgG2, IgG2 ratio suggesting other types of genetic influences than the MHC genes and has the capacity of the host responses towards the FMDV peptide.
Another study conducted on the Holstein-Charolais crossbred study population was tested for the commercial bovine respiratory syncytial virus (BRSV) vaccine. The analysis didn’t include the heritable factors so their responses towards the antibody contribution may not differ greatly. Moreover, the study also didn’t include any difference between the Charolais and Holstein calves. It has been understood and observed through these studies that the vaccine responses are a heritability of complex traits, therefore it is unlikely that it is controlled by a single gene. While catering to the host-pathogen interactions the majority of the genes controlling the vaccine responses will show variations and it is also expected that the individual genes will show polymorphism (Campbell & Heyer, 2007).
The understanding of microbiology has been greatly influenced by the study of genomics. The study of microbial strains has been offering new information and insight into pathogen evolution. Most importantly genotyping is influenced by gene variations and gene discovery and leads to designing the vaccination according to the latest needs (Moxon, 2002). It will ultimately help in monitoring the two-way communication between the pathogen and the host and will be recorded in the public database for the complete annotated genomic sequence.
However, there are still chances that the vaccination may not be completely able to eradicate the infection among the animals but are expected to reduce the severity of the result. There are chances that the vaccination may fail and the reason identified for its failure is not due to the lesser effectiveness of the vaccine but due to the improper timings or circumstances for inoculating the vaccine (DUFFY, KRZYCH, FRANCIS & FRIED, 2005). On such occasions, it may result in poor health responses and adverse effects on the health of the animals. The vaccination costs no matter how latest it is shall be lesser or more economical so that majority of the animals are receiving quality health and in return are able to provide quality meat for the consumers (Sampson, Rengarajan & Rubin, 2003).
Moreover, to make the process more reliable the vaccination shall be given with due consideration and communication between the livestock handler, farmer, and the developers of the vaccinations. Only in this way the vaccinations are considered to be more result oriented. Other protocols like the cleanliness of the environment, level of stress, environmental control, and density will help in better outcomes of the vaccination results. Thus, the recent transference of diseases from animals to humans has proved the fact that controlling the epidemic among humans and providing healthcare services in extremely expensive than controlling the expected epidemic among animals (Ali, Kroll & Langford, 2002). Animal vaccines and trials are not expensive and may not cost damage to any important loss of a large population. In contrast to humans where certainly expected trials expected to give positive results may fail in no time. Moreover, it becomes hard for the researchers to contain a specific form of the virus in the lab and later eliminate it. There is always a chance that any individual coming in contact with the host is able to receive this virus. Vaccination is the only way that could help in the spread of any new epidemic but for this purpose, the researchers need to stay ahead and learn and research more on the epidemic outbreaks so that they are able to control this issue within no time.
The concept of Vaccinogenomics in which the host genomics in vaccine research and integration of pathogens is expected to revolutionize the approach through which scientists have been opting for the introduction of and development of vaccination (Grandi & Zagursky, 2004). The stated research gives detailed profiling for increasing the effectiveness of animal vaccines. Future vaccine discovery research will be completely changed by identifying the genetic variances that control mechanisms of immune evasion, vaccine responsiveness, and disease resistance (Zhou & Xie, 2013).
The effectiveness of the vaccines shall be adequately commercialized so that every individual in need of the vaccines may understand and apprehend the message in detail. Since meat consumption has been increasing with time and due to this, the production of livestock has also increased. However, it has increased the chances of any new infection to outbreak affecting major populations. Either the consumer needs are reduced for the consumption of animal meat but in reality, it cannot be reduced. Therefore effective measures are required to be taken for ensuring that the livestock meat is safer and that no consumer of the animal meat is suspected of getting any type of virus.
Ali, T., Kroll, J., & Langford, P. (2002). Haemophilus influenzaeMicroarrays: Virulence and Vaccines. Comparative And Functional Genomics, 3(4), 358-361. http://dx.doi.org/10.1002/cfg.194
Barocchi, M., Censini, S., & Rappuoli, R. (2007). Vaccines in the era of genomics: The pneumococcal challenge. Vaccine, 25(16), 2963-2973. http://dx.doi.org/10.1016/j.vaccine.2007.01.065
Castiblanco, J., & Anaya, J. (2015). Genetics and Vaccines in the Era of Personalized Medicine. Current Genomics, 16(1), 47-59. http://dx.doi.org/10.2174/1389202916666141223220551
Campbell, A., & Heyer, L. (2007). Discovering genomics, proteomics, and bioinformatics. San Francisco: CSHL Press.
de Barsy, M., & Greub, G. (2013). Functional genomics of intracellular bacteria. Briefings In Functional Genomics, 12(4), 341-353. http://dx.doi.org/10.1093/bfgp/elt012
DUFFY, P., KRZYCH, U., FRANCIS, S., & Fried, M. (2005). Malaria vaccines: using models of immunity and functional genomics tools to accelerate the development of vaccines against. Vaccine, 23(17-18), 2235-2242. http://dx.doi.org/10.1016/j.vaccine.2005.01.046
Grandi, G., & Zagursky, R. (2004). The impact of genomics in vaccine discovery: achievements and lessons. Expert Review Of Vaccines, 3(6), 621-623. http://dx.doi.org/10.1586/14760522.214.171.1241
Hogue, D., & Ling, V. (1999). A Human Nucleobase Transporter-like cDNA (SLC23A1): Member of a Transporter Family Conserved from Bacteria to Mammals. Genomics, 59(1), 18-23. http://dx.doi.org/10.1006/geno.1999.5847
Izzo, A., & Schneider, R. (2010). Chatting histone modifications in mammals. Briefings In Functional Genomics, 9(5-6), 429-443. http://dx.doi.org/10.1093/bfgp/elq024
Jeanguenin, L., Lara-Núñez, A., Rodionov, D., Osterman, A., Komarova, N., & Rentsch, D. et al. (2011). Comparative genomics and functional analysis of the NiaP family uncover nicotinate transporters from bacteria, plants, and mammals. Functional & Integrative Genomics, 12(1), 25-34. http://dx.doi.org/10.1007/s10142-011-0255-y
Kussell, E. (2005). Bacterial Persistence: A Model of Survival in Changing Environments. Genetics, 169(4), 1807-1814. http://dx.doi.org/10.1534/genetics.104.035352
Ling, M., Ban, Y., Wen, H., Wang, S., & Ge, S. (2013). Conserved expression of natural antisense transcripts in mammals. BMC Genomics, 14(1), 243. http://dx.doi.org/10.1186/1471-2164-14-243
Lee, G., & Quan, F. (2016). Protection induced by early-stage vaccination with pandemic influenza virus-like particles. Vaccine, 34(33), 3764-3772. http://dx.doi.org/10.1016/j.vaccine.2016.06.011
Ling, H., Pelosi, A., & Walmsley, A. (2010). Current status of plant-made vaccines for veterinary purposes. Expert Review Of Vaccines, 9(8), 971-982. http://dx.doi.org/10.1586/erv.10.87
Ling, M., Ban, Y., Wen, H., Wang, S., & Ge, S. (2013). Conserved expression of natural antisense transcripts in mammals. BMC Genomics, 14(1), 243. http://dx.doi.org/10.1186/1471-2164-14-243
Moxon, R. (2002). Bacterial pathogen genomics and vaccines. British Medical Bulletin, 62(1), 45-58. http://dx.doi.org/10.1093/bmb/62.1.45
Mutoloki, S., Cooper, G., Marjara, I., Koop, B., & Evensen, Ø. (2010). High gene expression of inflammatory markers and IL-17A correlates with severity of injection site reactions of Atlantic salmon vaccinated with oil-adjuvanted vaccines. BMC Genomics, 11(1), 336. http://dx.doi.org/10.1186/1471-2164-11-336
Niu, Y., & Liang, S. (2008). Progress in gene transfer by germ cells in mammals. Journal Of Genetics And Genomics, 35(12), 701-714. http://dx.doi.org/10.1016/s1673-8527(08)60225-8
Ogholikhan, S., & Schwarz, K. (2016). Hepatitis Vaccines. Vaccines, 4(4), 6. http://dx.doi.org/10.3390/vaccines4010006
Reddy, S., Izumiya, Y., & Lupiani, B. (2017). Marek’s disease vaccines: Current status, and strategies for improvement and development of vector vaccines. Veterinary Microbiology, 206, 113-120. http://dx.doi.org/10.1016/j.vetmic.2016.11.024
Rupprecht, C., Nagarajan, T., & Ertl, H. (2016). Current Status and Development of Vaccines and Other Biologics for Human Rabies Prevention. Expert Review Of Vaccines, 15(6), 731-749. http://dx.doi.org/10.1586/14760584.2016.1140040
Sampson, S., Rengarajan, J., & Rubin, E. (2003). Bacterial genomics and vaccine design. Expert Review Of Vaccines, 2(3), 437-445. http://dx.doi.org/10.1586/147605126.96.36.1997
Sette, A., & Rappuoli, R. (2010). Reverse Vaccinology: Developing Vaccines in the Era of Genomics. Immunity, 33(4), 530-541. http://dx.doi.org/10.1016/j.immuni.2010.09.017
Spier, R. (2014). Vaccines protective against diseases caused by antibiotic-resistant bacteria: A pressing challenge to vaccinologists. Journal Of Vaccines & Vaccination, s1(01). http://dx.doi.org/10.4172/2157-7560.s1.019
Svartman, M., Stone, G., & Stanyon, R. (2005). Molecular cytogenetics discards polyploidy in mammals. Genomics, 85(4), 425-430. http://dx.doi.org/10.1016/j.ygeno.2004.12.004
Synthetic Genomics boosts RNA vaccines. (2017). C&EN Global Enterprise, 95(44), 15-15. http://dx.doi.org/10.1021/cen-09544-buscon12
Travis, J. (1999). Dam the Bacteria, Drugs and Vaccines Ahead. Science News, 155(19), 293. http://dx.doi.org/10.2307/4011493
Yuk, J., & Jo, E. (2014). Host immune responses to mycobacterial antigens and their implications for the development of a vaccine to control tuberculosis. Clinical And Experimental Vaccine Research, 3(2), 155. http://dx.doi.org/10.7774/cevr.2014.3.2.155
Zaja, V. (2014). The Fundamental Role of Bacteria and Yeasts in AIDS Progression. Journal Of Vaccines & Vaccination, 05(04). http://dx.doi.org/10.4172/2157-7560.1000238
Zhou, P., & Xie, J. (2013). Comparative genomics of theMycobacteriumsignaling architecture and implications for a novel live attenuated Tuberculosis vaccine. Human Vaccines & Immunotherapeutics, 10(1), 159-163. http://dx.doi.org/10.4161/hv.26268