Sequencing Data to Develop Recombinant Vaccines
Eradication and prevention of infectious diseases are achieved most often via vaccination. The common or traditional vaccines are made using the actual pathogen material, such as modified live or killed (inactivated) viruses. The use of these types of vaccines is sometimes associated with serious side effects. For some infectious agents, it is often difficult to develop vaccines using this approach, and there are limitations on the effectiveness of these vaccines. The use of recombinant vaccines is becoming an increasingly appealing alternative. These offer longer-term protection and are considered safer than conventional vaccines. Creation of these vaccines relies on the ability to identify pathogen proteins that can elicit an immune response. Pathogen DNA sequencing data provides valuable information and insight regarding the approach to recombinant vaccine development.
Conventional Vaccine Development
Vaccines act as pathogens to elicit an immune response without causing the actual disease. Specific pathogen proteins (antigens) trigger immune responses. Exposing the immune systems to these antigens primes the immune system to be quickly and efficiently respond if or when the body is confronted by the actual disease-causing pathogen. Modified-live pathogen vaccines are more effective than inactivated pathogen vaccines. However, they tend to have a lower safety margin than the inactivated type. Inactivated pathogen material does not replicate and tends to be safer, but their lower ability to elicit immune responses often requires the application of boosters to extend protection.
Recombinant vaccines are the result of the use of recombinant DNA technology. There are generally three types of recombinant vaccines, subunit, attenuated, and vector recombinant vaccines. Subunit vaccines are made from pathogen components such as proteins or DNA. Attenuated vaccines are made from genetically modified pathogenic microorganisms, but these do not cause disease. Vector vaccines are made from genetically modified viral vectors. In the case of vector vaccines, cloned genes from a pathogenic microorganism can be inserted into a virus genome (such as the vaccinia virus, the historic basis of the term vaccine). These then encode antigens that can elicit an immune response against the pathogen represented by the inserted cloned genes.
Pathogens, such as viruses, produce proteins that elicit immune responses. To produce protein vaccines, recombinant DNA is expressed in genetically-engineered microorganisms or other cell types to produce the key proteins used to develop the vaccine. For recombinant DNA vaccines, the DNA itself is used to develop the vaccine. The gene that corresponds to the antigen protein is cloned into a viral vector. After vaccination of an individual, a recombinant DNA is produced and is then expressed in the cells of the individual (producing the antigenic protein). To achieve all of this, information regarding the identity of the immune-activating antigen proteins is needed.
Use of Sequencing Data
Existing and emerging sequencing data is a key and crucial aspect of recombinant vaccine development. While there is data currently available, new data is sought to enhance recombinant vaccine development. The availability and continuing refinement of next-generation sequencing (NGS) technology allow the cost-effective generation of actionable data in record times. Visendi et al. have developed a comprehensive database of all available genomic data for Theileria parva (1) to bolster the discovery and development of a vaccine against East Coast fever.
In the search for a vaccine for the Zika virus, over 70 Zika virus genomic sequences are available for analysis to better understand the challenges to the development of a Zika vaccine and the evaluation of vaccine candidates (2). Research is active in the improvement of influenza vaccines. The World Health Organization provided consultation regarding the improvement of influenza vaccine selection (3). The report addressed the advances in NGS and whole genome sequencing of influenza viruses in the effort to develop the best vaccines.
Sequencing data is also used to confirm recombinant protein and DNA developed for testing their potential for use as vaccines. Javadi et al. evaluated a truncated hepatitis C protein as part of efforts to determine its use for vaccine development. Successful development of the construct was confirmed by sequencing prior to expression of the protein and purification.
The benefits of NGS are actively used by the vaccine research community in the search for the most effective and safe vaccines to replace those that are less effective vaccines and to develop new ones for diseases for which vaccines are still unavailable, such as for malaria, tuberculosis, and HIV infection. Genomic information provides insight into the characteristics of both the pathogen and the host. The data provided by NGS efforts are helping to reveal the mechanisms and factors related to viral mutation and survival and substantially support the development of new recombinant vaccines.
1. Visendi P, Ng’ang’a W, Bulimo W, Bishop R, Ochanda J, de Villiers EP. TparvaDB: a database to support Theileria parva vaccine development. Database: The Journal of Biological Databases and Curation. 2011;2011:bar015.
2. B.E. Dawes, C.A. Smalley, B.L. Tiner, D.W.C. Beasley, G.N. Milligan, L.M. Reece, J. Hombach, A.D.T. Barrett, “Research and development of Zika virus vaccines,” Npj Vaccines 1, 16007 (2016).
3. Alan H, Ian B, Nancy C, Ruben O D, Siddhivinayak H, Daniel J, Jacqueline K,
John M, Fernando M, Takato O, Tam JS, Anthony W, Richard W, Thedi Z, Wenqing Z.
Improving the selection and development of influenza vaccine viruses – Report of
a WHO informal consultation on improving influenza vaccine virus selection, Hong
Kong SAR, China, 18-20 November 2015. Vaccine. 2017 Feb 22;35(8):1104-1109.
4. Javadi F, Rahimi P, Modarressi MH, Bolhassani A, Ardestani MS, Sadat SM,
Aghasadeghi MR. Evaluation of Truncated HCV-NS3 Protein for Potential
Applications in Immunization and Diagnosis. Clin Lab. 2016 Jul 1;62(7):1271-1278.