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Laboratory of Infectious Diseases

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Alexander G. Pletnev, Ph.D., D.Sci.

Photo of Alexander G. Pletnev, Ph.D., D.Sci. 

Chief, Neurotropic Flaviviruses Section, LID

Major Areas of Research

  • Study of pathogenesis of flavivirus infection in the central nervous system
  • Development of novel approaches to restrict flavivirus neurotropism
  • Generation of attenuated vaccine candidates against disease caused by highly virulent neurotropic flaviviruses and evaluation of their safety, immunogenicity, and protective efficacy in animal models in preclinical studies, as well as assessment of safety for environment
  • Evaluation of safety and immunogenicity of live attenuated vaccine candidates in human clinical trials
 

Program Description

Flaviviruses, such as mosquito-borne West Nile, St. Louis encephalitis, and Japanese encephalitis viruses and tick-borne encephalitis viruses, are important neurotropic human pathogens, causing a devastating and often fatal neuroinfection. During the past two decades, both mosquito- and tick-borne flaviviruses have emerged in new geographic areas of the world where they were not previously endemic and have caused outbreaks of diseases in humans and domestic animals. Despite many attempts, licensed, safe, and effective live virus vaccines against these neurotropic viruses are not available.

The main goal and objective of our research projects is the development of safe live, attenuated virus vaccines that will be effective in preventing diseases caused by the highly virulent neurotropic viruses of the Flaviviridae family: tick-borne encephalitis virus, West Nile virus, and St. Louis encephalitis virus.

Biography

Dr. Pletnev earned his Ph.D. in 1983 in chemistry from the Russian Academy of Sciences, studying RNA polymerases. Following postdoctoral research at the Novosibirsk Institute of Bioorganic Chemistry, he served as chief of the laboratory of radiochemistry and the laboratory of molecular virology from 1984 to 1993 and became a professor in molecular biology in 1993. In 1990, he received his doctorate of sciences degree in biochemistry and molecular biology from the Russian Academy of Sciences. He joined the Laboratory of Infectious Diseases in 1993 as a visiting scientist and became a senior investigator in 2005.

Research Group

Heather Kenney
Guangping Liu
Olga Maximova
Natalia Teterina
Konstantin Tsetsarkin

Selected Publications

Teterina NL, Liu G, Maximova OA, Pletnev AG. Silencing of neurotropic flavivirus replication in the central nervous system by combining multiple microRNA target insertions in two distinct viral genome regions. Virology. 2014 May;456-457:247-58.

Maximova OA, Speicher JM, Skinner JR, Murphy BR, St Claire MC, Ragland DR, Herbert RL, Pare DR, Moore RM, Pletnev AG. Assurance of neuroattenuation of a live vaccine against West Nile virus: A comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine. Vaccine. 2014 May 30;32(26):3187-97.

Durbin AP, Wright PF, Cox A, Kagucia W, Elwood D, Henderson S, Wanionek K, Speicher J, Whitehead SS, Pletnev AG. The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers. Vaccine. 2013 Nov 19;31(48):5772-7

Heiss BL, Maximova OA, Thach DC, Speicher JM, Pletnev AG. MicroRNA targeting of neurotropic flavivirus: effective control of virus escape and reversion to neurovirulent phenotype. J Virol. 2012 May;86(10):5647-59.

Engel AR, Mitzel DN, Hanson CT, Wolfinbarger JB, Bloom ME, Pletnev AG. Chimeric tick-borne encephalitis/dengue virus is attenuated in Ixodes scapularis ticks and Aedes aegypti mosquitoes. Vector Borne Zoonotic Dis. 2011 Jun;11(6):665-74.

Heiss BL, Maximova OA, Pletnev AG. Insertion of microRNA targets into the flavivirus genome alters its highly neurovirulent phenotype. J Virol. 2011 Feb;85(4):1464-72.

Visit PubMed for a complete publication listing.

Patents

Pletnev AG, Murphy BM, Engel AR, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Antigenic chimeric tickborne encephalitis virus/dengue virus type 4 recombinant viruses. United States patent US 8,568,739. 29 Oct 2013.

Pletnev A, Chanock RM, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Full-length infectious cDNA clones of tick borne flavivirus. United States patent US 6,794,174. 21 Sep 2004.

Lai CJ, Bray M, Pletnev AG, Men R, Zhang YM, Eckels KH, Chanock RM, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Chimeric and/or growth-restricted flaviviruses. United States patent US 6,676,936. 13 Jan 2004.

Pletnev A, Men R, Chanock RM, Lai CJ, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Chimeric vaccine against tick-borne encephalitis virus. United States patent US 6,660,273. 9 Dec 2003.

Pletnev A, Men R, Chanock RM, Lai CJ, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Chimeric vaccine against tick-borne encephalitis virus. United States patent US 6,497,884. 24 Dec 2002.

Lai CJ, Bray M, Pletnev AG, Men R, Zhang YM, Eckels KH, Chanock RM, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Chimeric and/or growth-restricted flaviviruses. United States patent US 6,184,024. 6 Feb 2001.

Last Updated June 17, 2014

Last Reviewed June 05, 2012