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. 2010:2010:864029.
doi: 10.1155/2010/864029. Epub 2010 May 10.

Bioinformatics in new generation flavivirus vaccines

Penelope Koraka  1 , Byron E E Martina, Albert D M E Osterhaus
Affiliations

Bioinformatics in new generation flavivirus vaccines

Penelope Koraka et al. J Biomed Biotechnol. 2010.

Abstract

Flavivirus infections are the most prevalent arthropod-borne infections world wide, often causing severe disease especially among children, the elderly, and the immunocompromised. In the absence of effective antiviral treatment, prevention through vaccination would greatly reduce morbidity and mortality associated with flavivirus infections. Despite the success of the empirically developed vaccines against yellow fever virus, Japanese encephalitis virus and tick-borne encephalitis virus, there is an increasing need for a more rational design and development of safe and effective vaccines. Several bioinformatic tools are available to support such rational vaccine design. In doing so, several parameters have to be taken into account, such as safety for the target population, overall immunogenicity of the candidate vaccine, and efficacy and longevity of the immune responses triggered. Examples of how bio-informatics is applied to assist in the rational design and improvements of vaccines, particularly flavivirus vaccines, are presented and discussed.

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Figures

Figure 1
Figure 1
(a) Flavivirus genomic RNA encoding one long ORF cleaved co- and post-translationally into three structural and seven nonstructural proteins. The viral genome is flanked by 5′and 3′UTRs which play an important role in virus transcription and replication. (b) Three dimensional structure of the monomeric form of the E protein of DENV-2. Each monomer is divided into three discernable domains (DI, II and III). Serocomplex and group specific cross reactive epitopes are mainly located on DI and II. DIII is the receptor binding domain and contains mainly type specific epitopes. The potent neutralizing epitopes are located at the lateral site of DIII.
Figure 2
Figure 2
Steps involved in the rational design of vaccines. A number of parameters should be taken into account from choosing the right immunogen until the selection of candidate vaccines for clinical trials. Several bioinformatics tools can be applied in this process to assist in the improvement of antigen selection, maximizing expression, determination of immunogenicity and selection of candidate vaccines.
Figure 3
Figure 3
Prediction of RNA secondary structure of the 3′UTR of DENV-3 strain H87 (DENV-2 Jamaica strain) using the GA algorithm included in the STAR software package. In the top panel is depicted the predicted structure of the naturally occurring strain (shown with arrows the predicted pseudoknot and the conserved LSH structures), bottom panel: predicted structure after in silico introduction of a 29-nt deletion in the proximal part of the UTR. The LSH is preserved but the pseudoknot is lost after deletion. LSH: long stable hairpin, ps: pseudoknot.
Figure 4
Figure 4
(a) A basic expression plasmid showing the CMV promoter, multiple cloning sites (MCS) and a BGH polyadenylation site, (b) Predicted signal peptide sequence for the WNV E protein. The signal peptide probability is determined by the positive polarity of the n-region, the hydrophobicity of the h-region and the uncharged amino acids occupying positions −1 and −3 in the c-region. The cleavage site is located in the c-region and is determined by the physicochemical characteristics and length of the n- and h-regions.
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