Overview of computational vaccinology: vaccine development through information technology

J Appl Genetics DOI 10.1007/s13353-014-0265-2 MICROBIAL GENETICS • REVIEW Overview of computational vaccinology: vaccine development through information technology Nishita Vaishnav & Aparna Gupta & Sneha Paul & Georrge J. John Received: 9 August 2014 / Revised: 17 November 2014 / Accepted: 8 December 2014 # Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2014 Abstract Pathogenic organisms, causes of various infectious diseases, possess a rich repository of antigenic proteins that engender an immune response in a host. These types of diseases are usually treated with the use of pharmaceuticals; unfortunately, many of these also have a potential to induce fatal side effects, especially allergic responses in the diseased host. In addition, many pathogens evolve (by selective survival) single or multi-drug resistance (MDR). Therefore, a means to prevent the host from becoming susceptible to the pathogen from the onset, rather than trying to devise pharmacologic protocols to treat an ongoing infection, are increasingly seen as desirable to reduce the incidence of infectious diseases altogether. To this end, cost-effective development and use of “safe” vaccines is key. This paper provides an overview on the new and expanding area of computational vaccinology and a brief background on pathogen antigenicity, identification of pathogen-specific antigens, and screening of candidate antigens using various tools and databases developed in the recent past. Keywords Infection . In silico . Prediction . Vaccine Communicated by: Agnieszka Szalewska-Palasz N. Vaishnav : A. Gupta : S. Paul : G. J. John (*) Department of Bioinformatics, Christ College, Rajkot, Gujarat, India e-mail: G. J. John Department of Biochemistry and Molecular Biology, University Clinic of Bonn (UKB), Bonn, Germany Present Address: S. Paul Centennial College, Toronto, Toronto, ON, Canada Introduction Every year, approximately 3.5 million people die worldwide due to infectious diseases (WHO 2014). Infection is defined as an invasion of a host’s tissues by disease-causing organisms, their multiplication, and the reaction of host tissues to these organisms/toxins they produce. Infections can be caused by a multitude of microbes and macro-parasites, and are classified on the basis of the causative agents, i.e., bacterial, protozoal, viral, fungal, etc., transferred among hosts by numerous means. For example, respiratory diseases are often acquired by a naive host when in contact with aerosolized droplets containing the organism that are released from an infected host during sneezing, coughing, or talking. On the other hand, gastrointestinal diseases are routinely acquired by consuming food\water directly contaminated with pathogens, or by the inadvertent transmission by inappropriate usage of sanitary techniques during the handling of food and liquid meant for consumption. These types of diseases, when diagnosed, are treated with various pharmaceuticals such as penicillin, Cephalosporin, Glycopeptide, and Macrolide; unfortunately, many of these drugs also have the potential to induce fatal side effects (Poppe 2001; Nebeker et al. 2004; Kronman et al. 2012), especially those that induce allergic responses, in the diseased host. Nevertheless, even with a plethora of drugs to choose from, many pathogens can develop single/multi-drug resistance (MDR) through selective survival (Sood and Arti 2008). Therefore, a means to prevent the host from becoming susceptible to the pathogen from the onset, rather than trying to devise pharmacologic protocols to treat an ongoing infection, have increasingly been seen as desirable throughout the world to reduce the incidence of infectious diseases altogether. To this end, the practical/cost-effective development and use of “safe” vaccines is key. J Appl Genetics Vaccine: a shielding measure When a pathogen/antigen is introduced in a host, the vaccine tricks (i.e., using a “non-real” version of the organism) the host immune system and educates it about how to respond at that moment/in the future against the same agent (NIAID 2013), thus inducing a cell-mediated/ humoral immune response. For example, a viral vaccine contains an undermined form of the virus that neither causes a disease nor replicates. Since the host macrophages are unaware that the vaccine virus is undermined, it processes it as it would any other antigen/pathogen. The macrophages then induce the viral antigen to T- and Bcells in the lymph nodes. In turn, after several steps including activation and differentiation, virus-specific Tcells activate B-cells to ultimately produce anti-viral antibodies. While the weakened viruses in the vaccine are quickly eliminated, the host is left with a set of memory T- and B-cells which are imperative to opposing the specific viral disease should the host ever actually encounter the live organism. In the past, vaccines have been developed using different strategies, each with their own disadvantages and advantages. These vaccines are of the following types: Live or attenuated These vaccines enclose the living microbe in a weakened form so that it cannot induce the actual disease. For example, vaccines against measles, mumps, and chickenpox are live, attenuated vaccines. They provoke more long-lasting humoral and cellular immune responses and are preferred for healthy adults, not immunocompromised people (Sinha and Bhattacharya 2014). The limitation here is that while the microbes are live and attenuated, they still have the tendency to change and potentially relapse to a virulent form. In addition, the habituated live attenuated vaccine necessitates refrigeration to stay viable; this makes their use costly and problematic in parts of the world where optimal facilities are not available. It is more difficult to develop these vaccines for bacteria as they have thousands of genes and are hence much harder to control (Alexandersen 1996; NIAID 2013). The other concern with live or attenuated vaccines is that they can confound disease investigation, based on serological testing which leads to false positives (Pluimers 2004). Inactivated Since dead microbes in an inactivated vaccine are treated with chemicals, heat, or radiation, they lose the ability to replicate and cause infection. This inactivated vaccine contains pathogen recognition patterns capable of initiating innate immune responses (van Duin et al. 2006). Vaccines for polio, plague, TB, etc. are of inactivated type (Immunization 2014). The storage of these vaccines doesn’t require refrigeration, making them useful and safer for larger populations or easier to deliver to remote areas of the world. However, the major constraint for the use of such vaccine is that they lead to generation of weaker immune responses, and therefore, there is a need for recurring dosages or booster shots due to diminishing immunity. In order to overcome this limitation, inactivated vaccines are often administered along with an a (...truncated)