Abdul Malik Setiawan, MD, 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 are considered as normal flora for the host, some strains have the ability to cause disease. 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 the gastrointestinal tract was believed to cause many damages to the people in terms of health problems and financial matters (2). In addition, an increase in the number of antimicrobial resistance ExPEC in the 2000s began to draw much attention from the health community about the importance of human protection against this pathogen (3).
Vaccination has been proven to be the most powerful way to protect human race from deadly infectious diseases like smallpox or polio. Moreover, the advance of molecular technology in the vaccine industry nowadays provides greater opportunities for scientists 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 vaccine candidate who had passed a clinical trial. This paper will discuss what scientists have 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 were not founded in non-pathogenic E. coli. From those genes, they use a "subtractive reverse approach" to predict 230 antigens potential to become vaccine candidates. The prediction is 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 was then proven to be protective against different strains of ExPEC with protective efficacy ranging 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 that it is widely distributed 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 due to lack of T2SS region in their genome. The T2SS region can be considered as a virulence factor that distinguishes non-pathogenic E. coli from the pathogenic E. Coli (1). Therefore, this antigen would not induce host immunity against non-pathogenic E. coli which is normal human flora.
The “reverse vaccinationology” approach in Moriel et al. study is the important part that should be underlined in this report. The advance of genomic technologies eventually provides benefits in vaccine development. The first successful vaccine candidates using this method were Meningococcal B (MenB) vaccine. Other genome based approaches such as refined reverse vaccinology, transcriptomics, functional genomics and proteomics are being used nowadays to develop novel vaccine candidates (5). Furthermore, the emergence of bioinformatic sciences provides a tool for genomic based vaccine development to elaborate molecular biology with simple computational technologies and leads to rapid vaccine production compared with conventional based approaches.

Reference List
1. Moriel DG, Bertoldi I, Spagnuolo A, Marchi S, Rosini R, Nesta B, et al. Identification of protective and widely 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. JDD pitout. 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.