Zoltan Vajo Explained

Zoltan Vajo is a Hungarian/American scientist, best known [1] for his contributions to the Human Genome Project, including cloning the COQ7 gene,[2] characterizing the human CLK-1 timing protein cDNA [3] and its potential effect on aging,[4] and research on the molecular and genetic background of skeletal dysplasias and fibroblast growth factor receptor 3 disorders, including Achondroplasia, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), Thanatophoric dysplasia, Muenke coronal craniosynostosis and Crouzon syndrome[5] as well as more recently on genetically engineered insulin analog molecules, including their structure, metabolic effects and cellular processing [6] and the role of recombinant DNA technology in the treatment of diabetes.[7]

Contributions

Vajo et al. in 1999 cloned COQ7 from human heart. They found that the predicted protein contains 179 amino acids, is mostly helical, and contains an alpha-helical membrane insertion. It has a potential N-glycosylation site, a phosphorylation site for protein kinase C and another for casein kinase II, and 3 N-myristoylation sites. Northern blot analysis detected 3 transcripts; a 1-kb transcript was predominant in heart, and a 3-kb transcript was predominant in skeletal muscle, kidney, and pancreas.[8]

Vajo et al. found in 2000 that alterations in venous reactivity to alpha- and beta-adrenergic, nitric oxide (NO)-dependent, and other drugs are present in many genetically determined and acquired conditions, such as hypertension, smoking, and aging.[9]

In 2001, Fawcett, Bennett, Hamel, Vajo and Duckworth showed that the effect of human insulin and its analogues on protein degradation vary significantly in different cell types and with different experimental conditions. The differences seen in the action of the insulin analogues cannot be attributed to binding differences only. Post-receptor mechanisms, including intracellular processing and degradation, must be also considered.[10] Since then, recombinant DNA technology and the use of insulin analogues has become a major part of the treatment of diabetes.[11]

More recently (2007-2019), Vajo et al. developed novel influenza vaccines based on reverse genetics technology, including vaccines against the H5N1 bird flu and the H1N1 swine flu viruses, as well as seasonal influenza.[12] In preparation for the influenza pandemic, Vajo and Jankovics showed that instead of the conventionally used split virion or subunit vaccines, lower doses of whole virus vaccines are able to induce sufficient immune responses even against newly emerged influenza virus strains in pediatric [13] adult [14] and elderly patients, without increasing the rate of adverse events. This was achieved in part by using aluminum phosphate as an adjuvant. These vaccines were used to combat the 2009 swine flu pandemic.[15] The technologies developed during the preparation for an influenza pandemic were successfully translated into the production of reduced dose, seasonal trivalent influenza vaccines, which since have been licensed for clinical use.[16] [17]

Important publications

In the media

On CNN, July 29, 2007

The Doctors' Channel, December 23, 2008

The Daily Miner, April 16, 2010: KRMC doctor on Swiss flu vaccine safety board

The Daily Miner, July 12, 2010

Notes and References

  1. OMIM - Online Mendelian Inheritance in Man. ID 601683. https://www.ncbi.nlm.nih.gov/omim/601683
  2. NCBI - National Center for Biotechnology and Information https://www.ncbi.nlm.nih.gov/nuccore/AF053770.1
  3. NCBI - National Center for Biotechnology and Information https://www.ncbi.nlm.nih.gov/nuccore/AF032900.1
  4. Rustin P, Von Kleist-Retzow, J.-C, Vajo Z, Rotig A, Munnich A. . For debate: defective mitochondria, free radicals, cell death, aging-reality or myth-ochondria? . Mechanisms of Ageing and Development . 114 . 3 . 201–206 . April 2000 . 10802124 . 10.1016/S0047-6374(00)00102-0. 27395914 .
  5. Vajo Z, Francomano CA, Wilkin DJ . The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans . Endocrine Reviews . 21 . 1 . 23–39 . February 2000 . 10.1210/edrv.21.1.0387 . 10696568 . 43581040 . free .
  6. Vajo Z, Duckworth W . Genetically engineered insulin analogs: Diabetes in the new millennium . Pharmacological Reviews . 52 . 1 . 1–9 . March 2000. 10699152 .
  7. Vajo Z, Fawcet J, Duckworth W . Recombinant DNA technology in the treatment of diabetes: insulin analogs. . Endocrine Reviews . 22 . 5 . 706–17 . October 2001 . 11588149 . 10.1210/edrv.22.5.0442 . free .
  8. Vajo Z, King LM, Jonassen T, etal . Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging . Mammalian Genome . 10 . 10 . 1000–4 . October 1999 . 10501970 . 10.1007/s003359901147. 13800512 .
  9. Vajo Z, Dachman W, Szekacs B . Alterations of venous drug reactivity in humans: acquired and genetic factors. . Angiology . 51 . 5 . 361–6 . May 2000 . 10826852 . 10.1177/000331970005100502. 2040036 .
  10. Fawcett J, Hamel FG, Bennett RG, Vajo Z, Duckworth WC . Insulin and analogue effects on protein degradation in different cell types. Dissociation between binding and activity . Journal of Biological Chemistry . 276 . 15 . 11552–8 . April 2001. 11116143 . 10.1074/jbc.M007988200. free .
  11. Vajo Z, Fawcett J, Duckworth WC . Recombinant DNA technology in the treatment of diabetes: insulin analogs. . Endocr. Rev. . 22 . 5 . 706–17 . October 2001 . 11588149 . 10.1210/edrv.22.5.0442. free .
  12. Vajo Z, Wood J, Kosa L, Szilvasy I, Paragh G, Pauliny Z, Bartha K, Visontay I, Kis A, Jankovics I . A single-dose influenza A (H5N1) vaccine safe and immunogenic in adult and elderly patients: an approach to pandemic vaccine development.. J. Virol. . 84 . 3 . 1237–42 . February 2010. 19906909 . 10.1128/JVI.01894-09 . 2812344.
  13. Vajo Z, Kosa L, Szilvasy I, Pauliny Z, Bartha K, Visontay I, Kis A, Tarjan I, Rozsa N, Jankovics I . Safety and immunogenicity of a prepandemic influenza A (H5N1) vaccine in children. . Pediatric Infectious Disease Journal . 27 . 12 . 1052–6 . December 2008 . 18978514 . 10.1097/INF.0b013e3181861dd7. 12628452 .,
  14. Vajo Z, Kosa L, Visontay I, Jankovics M, Jankovics I . Inactivated whole virus influenza A (H5N1) vaccine . Emerg Infect Dis . 13 . 5 . 807–8 . May 2007. 18044056 . 10.3201/eid1305.061248 . 2738456.,
  15. Vajo Z, Tamas F, Sinka L, Jankovics I . Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009-10 influenza season: a multicentre, randomised controlled trial . Lancet . 375 . 9748 . 49–55 . January 2010. 20018367 . 10.1016/S0140-6736(09)62039-0. 19512258 .
  16. Vajo Z, Tamas F, Jankovics I . A reduced-dose seasonal trivalent influenza vaccine is safe and immunogenic in adult and elderly patients in a randomized controlled trial. . Clin Vaccine Immunol . 19 . 3 . 313–8 . March 2012 . 22219315 . 10.1128/CVI.05619-11 . 3294605.,
  17. Vajo Z, Kalabay L, Vajo P, Balaton G, Rozsa N, Torzsa P . Licensing the first reduced, 6 µg dose whole virion, aluminum adjuvanted seasonal influenza vaccine - A randomized-controlled multicenter trial. . Vaccine . 37 . 2 . 258–264 . Jan 2019 . 30497837 . 10.1016/j.vaccine.2018.11.039 . 54166208 .,

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