Abdul Malik Setiawan, M.D, M.Infect.Dis.
School of Medicine, Faculty of Medicine and Health Sciences. State Islamic University Maulana Malik Ibrahim Malang
One of the most common microorganisms founded in the human gut is Escherichia coli. While most strains of these microorganisms considered as a normal flora to the host, some strains have the ability to cause diseases. There are three main groups of these traits according to their pathogenicity; commensal, intestinal pathogenic E. coli and extraintestinal pathogenic E. coli (ExPEC) (1).
The ability of ExPEC to attack and colonize in many different sites other than gastrointestinal tracts was believed to cause many damages to the people in terms of health problems and financial matters (2). In addition, an increase in number of antimicrobial resistance ExPEC in 2000s starting to draw many attentions from health community about the importance of human protection against this pathogen (3).
Vaccination has proven to be the most powerfull way to protect human race from deadly infectious diseases like smallpox or polio. Moreover, the advance of molecular technology in vaccine industry nowadays provide greater opportunities for the scientist to enhance vaccine development on various diseases (4). The availability of whole genome sequences of E. coli could lead to potential vaccine candidates by studying the genomic differences between non pathogenic and extraintestinal pathogenic E. coli (1). Until today, there was no single vacine candidates have passed a clinical trial. This paper will discuss about what scientists have been done regarding ExPEC vaccine development.
Moriel et al. (2009) in their study has identified 19 groups of genes also known as “genomic islands” in ExPEC that was not founded in non-pathogenic E. coli. From those genes, they use “subtractive reverse approach” to predict 230 antigens potential to become vaccine candidates. The prediction based on bioinformatic analysis to filter which antigens were surface associated or secreted. Nine antigens out of 230 antigens were proven to have in vivo protection to the mouse models that were challenged by pathogenic strains of E. coli (1).
The protection levels within nine antigens were varying from 13 % to 82 %. Most protective candidates with the highest level of protection (82 %) were ECOK1_3385 antigen. This antigen then proven to be protective against different strains of ExPEC with protective efficacy ranged from 43% to 78%. The protection obtained from both active and passive immunization could prevent bacteraemia and mortality. Moriel et al. believed that antigen encoded by ECOK1_3385 gene is a broadly protective vaccine candidate for ExPEC (1).
The unique fact about ECOK1_3385 gene is it widely spread not only in ExPEC but also in Intestinal pathogenic E. coli (InPEC) and in non-pathogenic E. coli. However, the antigen is not secreted in non-pathogenic E. coli because lack of T2SS region in their genome. T2SS region can be considered as a virulence factor that distinguished non-pathogenic E. coli to the pathogenic E. Coli (1). Therefore, this antigen would not induce host immunity against non-pathogenic E. coli which is human normal flora.
The “reverse vaccinology” approach in Moriel et al. study is the important part that should be underlined in this report. The advance of genomic technologies eventually gives benefits in vaccine development. The first successful vaccine candidates using this method is Meningococcal B (MenB) vaccine. Other genome based approaches such as refined reverse vaccinology, transcriptomic, functional genomic and proteomic are being used nowadays to develop novel vaccine candidates (5). Furthermore, the emerge of bioinformatic sciences provide a tool for genomic based vaccine development to elaborate molecular biology with simple computational technologies and lead to rapid vaccine production compared with conventional based approaches.
1. Moriel DG, Bertoldi I, Spagnuolo A, Marchi S, Rosini R, Nesta B, et al. Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proceedings of the National Academy of Sciences. 2010 May 18, 2010;107(20):9072-7.
2. Smith JL, Fratamico PM, Gunther NW. Extraintestinal pathogenic Escherichia coli. Foodborne pathogens and disease. 2007;4(2):134-63.
3. Pitout JDD. Extraintestinal pathogenic Escherichia coli: an update on antimicrobial resistance, laboratory diagnosis and treatment. Expert Review of Anti-Infective Therapy. 2012 Oct 2012;10(10):1165-76. PubMed PMID: 1266802195; 23199402.
4. Plotkin SA. Vaccines: past, present and future. Nat Med. 2005 April 2005;11(4):S5-S11.
5. Rinaudo CD, Telford JL, Rappuoli R, Seib KL. Vaccinology in the genome era. Journal of Clinical Investigation. 2009 Sep 2009;119(9):2515-25.