Synthetic biology: Impact on the design of innovative vaccines

Conventional vaccine design strategies mainly focus on live-attenuated vaccines, inactivated microorganisms, and subunits thereof comprising purified components or recombinantly expressed proteins, mostly formulated with adjuvants. Although generally very efficient, these approaches are suboptimal or unfeasible for some infectious diseases. Over the past years new technologies to vaccine development have evolved, often utilizing design principles and construction technologies of synthetic biology. The contribution of synthetic biology to vaccine development comprises algorithms for accelerated in silico identification of relevant protein candidates, in silico design of novel immunogens with improved expression, safety and immunogenicity profiles as well as in silico design of (1) nucleic acid based, (2) vectored and (3) live-attenuated vaccines. Furthermore, synthetic biology enables economic and rapid chemical synthesis of DNA encoding the immunogens designed in silico, and their efficient assembly with delivery systems to obtain vectored vaccines. Altogether, synthetic biology can help to develop improved vaccine candidates in considerably less time compared to conventional approaches.

[1]  Thomas H Segall-Shapiro,et al.  Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome , 2010, Science.

[2]  J. R. Coleman,et al.  Virus Attenuation by Genome-Scale Changes in Codon Pair Bias , 2008, Science.

[3]  A. Vincent,et al.  Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region , 2006, Journal of Virology.

[4]  S. Held,et al.  RNA Vaccines in Cancer Treatment , 2010, Journal of biomedicine & biotechnology.

[5]  G. Pantaleo,et al.  Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens , 2009, Journal of Virology.

[6]  J. Venter,et al.  Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. , 2000, Science.

[7]  S. McCormack,et al.  An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses , 2008, The Journal of experimental medicine.

[8]  Rino Rappuoli,et al.  Reverse vaccinology. , 2000, Current opinion in microbiology.

[9]  D. Raab,et al.  The GeneOptimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization , 2010, Systems and Synthetic Biology.

[10]  Evan Powell,et al.  Comparative Genomic Analyses of Seventeen Streptococcus pneumoniae Strains: Insights into the Pneumococcal Supragenome , 2007, Journal of bacteriology.

[11]  Søren Brunak,et al.  Clustering Patterns of Cytotoxic T-Lymphocyte Epitopes in Human Immunodeficiency Virus Type 1 (HIV-1) Proteins Reveal Imprints of Immune Evasion on HIV-1 Global Variation , 2002, Journal of Virology.

[12]  R. Wagner,et al.  Preclinical evaluation of the immunogenicity of C-type HIV-1-based DNA and NYVAC vaccines in the Balb/C mouse model. , 2009, Viral immunology.

[13]  O. Lund,et al.  Definition of supertypes for HLA molecules using clustering of specificity matrices , 2004, Immunogenetics.

[14]  Vishvanath Nene,et al.  Faculty Opinions recommendation of Live attenuated influenza virus vaccines by computer-aided rational design. , 2010 .

[15]  C. Ockenhouse,et al.  Effect of Codon Optimization on Expression Levels of a Functionally Folded Malaria Vaccine Candidate in Prokaryotic and Eukaryotic Expression Systems , 2003, Infection and Immunity.

[16]  Feng Gao,et al.  Diversity Considerations in HIV-1 Vaccine Selection , 2002, Science.

[17]  Kevin Marsh,et al.  Immunity to malaria: more questions than answers , 2008, Nature Immunology.

[18]  R. Wagner,et al.  Impact of Codon Usage Modification on T Cell Immunogenicity and Longevity of HIV-1 Gag-Specific DNA Vaccines , 2003, Intervirology.

[19]  D. Weiner,et al.  Immunogenicity of novel consensus-based DNA vaccines against avian influenza. , 2007, Vaccine.

[20]  M. Graf,et al.  Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein , 2001, Journal of Virology.

[21]  A. Paul,et al.  Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template , 2002, Science.

[22]  P. Chiarella,et al.  Recent advances in epitope design for immunotherapy of cancer. , 2009, Recent patents on anti-cancer drug discovery.

[23]  H. Tettelin,et al.  Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen , 2005, Science.

[24]  Jaideep P. Sundaram,et al.  Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome". , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Steven Skiena,et al.  Reduction of the Rate of Poliovirus Protein Synthesis through Large-Scale Codon Deoptimization Causes Attenuation of Viral Virulence by Lowering Specific Infectivity , 2006, Journal of Virology.

[26]  J. Sattabongkot,et al.  A Novel Chimeric Plasmodium vivax Circumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites , 2006, Infection and Immunity.

[27]  Persephone Borrow,et al.  The immune response during acute HIV-1 infection: clues for vaccine development , 2009, Nature Reviews Immunology.

[28]  Gordon Ada,et al.  Overview of vaccines and vaccination , 2005, Molecular biotechnology.

[29]  L I Karpenko,et al.  Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+ T cell responses. , 2010, Molecular immunology.

[30]  Morten Nielsen,et al.  Identification of CD8+ T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL , 2010, PloS one.

[31]  T. Ikemura Codon usage and tRNA content in unicellular and multicellular organisms. , 1985, Molecular biology and evolution.

[32]  Bette Korber,et al.  Mosaic HIV-1 Vaccines Expand the Breadth and Depth of Cellular Immune Responses in Rhesus Monkeys , 2010, Nature Medicine.

[33]  I. Frazer,et al.  Codon modified human papillomavirus type 16 E7 DNA vaccine enhances cytotoxic T-lymphocyte induction and anti-tumour activity. , 2002, Virology.

[34]  M. Graf,et al.  Rev-independent expression of synthetic gag-pol genes of human immunodeficiency virus type 1 and simian immunodeficiency virus: implications for the safety of lentiviral vectors. , 2000, Human gene therapy.

[35]  Stefan H E Kaufmann,et al.  Future vaccination strategies against tuberculosis: thinking outside the box. , 2010, Immunity.

[36]  D. Weiner,et al.  First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. , 1998, The Journal of infectious diseases.

[37]  J. Sidney,et al.  Identification of broad binding class I HLA supertype epitopes to provide universal coverage of influenza A virus. , 2010, Human immunology.

[38]  Bjoern Peters,et al.  Design and utilization of epitope-based databases and predictive tools , 2010, Immunogenetics.

[39]  R. Rappuoli,et al.  A universal vaccine for serogroup B meningococcus. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Bjoern Peters,et al.  HLA class I supertypes: a revised and updated classification , 2008, BMC Immunology.

[41]  S. Salzberg,et al.  Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution , 2005, Nature.

[42]  L. Falo,et al.  Transcriptional IL-15-directed in vivo DC targeting DNA vaccine , 2009, Gene Therapy.

[43]  M. Houghton,et al.  Prospects for a vaccine against the hepatitis C virus , 2005, Nature.

[44]  Rino Rappuoli,et al.  The use of genomics in microbial vaccine development , 2009, Drug Discovery Today.

[45]  Jan Kubicek,et al.  Gene optimization mechanisms: A multi-gene study reveals a high success rate of full-length human proteins expressed in Escherichia coli , 2010, Protein science : a publication of the Protein Society.

[46]  R. Steinman,et al.  The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. , 2008, The Journal of clinical investigation.

[47]  B. L. Han,et al.  Synthetic biology for translational research. , 2010, American journal of translational research.