Top

Virology Journal

Published in:

Open Access 01-12-2009 | Research

Improved Efficacy of a Gene Optimised Adenovirus-based Vaccine for Venezuelan Equine Encephalitis Virus

Authors: Amanda J Williams, Lyn M O'Brien, Robert J Phillpotts, Stuart D Perkins

Published in: Virology Journal | Issue 1/2009

Abstract

Background

Optimisation of genes has been shown to be beneficial for expression of proteins in a range of applications. Optimisation has increased protein expression levels through improved codon usage of the genes and an increase in levels of messenger RNA. We have applied this to an adenovirus (ad)-based vaccine encoding structural proteins (E3-E2-6K) of Venezuelan equine encephalitis virus (VEEV).

Results

Following administration of this vaccine to Balb/c mice, an approximately ten-fold increase in antibody response was elicited and increased protective efficacy compared to an ad-based vaccine containing non-optimised genes was observed after challenge.

Conclusion

This study, in which the utility of optimising genes encoding the structural proteins of VEEV is demonstrated for the first time, informs us that including optimised genes in gene-based vaccines for VEEV is essential to obtain maximum immunogenicity and protective efficacy.

Available only for authorised users

Weaver SC, Ferro C, Barrera R, Boshell J, Navarro JC: Venezuelan equine encephalitis. Annual Review of Entomology 2004, 49: 141-174. 10.1146/annurev.ento.49.061802.123422CrossRefPubMed

Klietmann WF, Ruoff KL: Bioterrorism: implications for the clinical microbiologist. Clin Microbiol Rev 2001, 14: 364-81. 10.1128/CMR.14.2.364-381.2001PubMedCentralCrossRefPubMed

Alibek K: The Emerging BW Threat: Lessons from the Russian Offensive BW R&D Program, 1945 to 1992. Maxwell AFB, Alabama;

Stockholm International Peace Research Institute: The problem of chemical and biological warfare. In CB Weapons Today. Volume 2. Almqvist and Wiksell, Stockholm; 1973.

Hawley RJ, Eitzen EM Jr: Biological weapons – a primer for microbiologists. Annu Rev Microbiol 2001, 55: 235-53. 10.1146/annurev.micro.55.1.235CrossRefPubMed

Hilleman MR: Overview: cause and prevention in biowarfare and bioterrorism. Vaccine 2002, 20: 3055-67. 10.1016/S0264-410X(02)00300-6CrossRefPubMed

Johnson KM, Martin DH: Venezuelan equine encephalitis. Adv Vet Sci Comp Med 1974, 18: 79-116.PubMed

Pittman PR, Makuch RS, Mangiafico JA, Cannon TL, Gibbs PH, Peters CJ: Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine. Vaccine 1996, 14: 337-343. 10.1016/0264-410X(95)00168-ZCrossRefPubMed

Fine DL, Roberts BA, Terpening SJ, Mott J, Vasconcelos D, House RV: Neurovirulence evaluation of Venezuelan equine encephalitis (VEE) vaccine candidate V3526 in nonhuman primates. Vaccine 2008, 26: 3497-3506. 10.1016/j.vaccine.2008.04.044CrossRefPubMed

10.

Reed DS, Lind CM, Lackemeyer MG, Sullivan LJ, Pratt WD, Parker MD: Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus. Vaccine 2005, 23: 3139-3147. 10.1016/j.vaccine.2004.12.023CrossRefPubMed

11.

Pratt WD, Davis NL, Johnston RE, Smith JF: Genetically engineered, live attenuated vaccines for Venezuelan equine encephalitis: testing in animal models. Vaccine 2003, 21: 3854-62. 10.1016/S0264-410X(03)00328-1CrossRefPubMed

12.

Gale S: Interscience Conference on Antimicrobial Agents and Chemotherapy – 48th Annual Meeting and Infectious Diseases Society of America – 46th Annual Meeting Updates on therapeutic research – Part 1. Idrugs 2009, 12: 1-2.PubMed

13.

Strauss JH, Strauss EG: The alphaviruses: gene expression, replication, and evolution. Microbiol Mol Biol Rev 1994, 58: 491-562.

14.

Phillpotts RJ, O'Brien L, Appleton RE, Carr S, Bennett A: Intranasal immunisation with defective adenovirus serotype 5 expressing the Venezuelan equine encephalitis virus E2 glycoprotein protects against airborne challenge with virulent virus. Vaccine 2005, 23: 1615-23. 10.1016/j.vaccine.2004.06.056CrossRefPubMed

15.

Griffin D, Levine B, Tyor W, Ubol S, Despres P: The role of antibody in recovery from alphavirus encephalitis. Immunological Reviews 1997, 159: 155-161. 10.1111/j.1600-065X.1997.tb01013.xCrossRefPubMed

16.

Elvin SJ, Bennett AM, Phillpotts RJ: Role for mucosal immune responses and cell-mediated immune functions in protection from airborne challenge with Venezuelan equine encephalitis virus. J Med Virol 2002, 67: 384-93. 10.1002/jmv.10086CrossRefPubMed

17.

Graf M, Schoedl T, Wagner R: Rationals of Gene Design and de novo Gene Construction. In Systems Biology and Synthetic Biology. Edited by: Fu P, Latterich M, Panke S. Wiley; 2009.

18.

Zolotukhin S, Potter M, Hauswirth WW, Guy J, Muzyczka N: A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J Virol 1996, 70: 4646-4654.PubMedCentralPubMed

19.

Riemenschneider J, Garrison A, Geisbert J, Jahrling P, Hevey M, Negley D, Schmaljohn A, Lee J, Hart MK, Vanderzanden L, et al.: Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus. Vaccine 2003, 21: 4071-80. 10.1016/S0264-410X(03)00362-1CrossRefPubMed

20.

Perkins SD, O'Brien LM, Phillpotts RJ: Boosting with an adenovirus-based vaccine improves protective efficacy against Venezuelan equine encephalitis virus following DNA vaccination. Vaccine 2006, 24: 3440-3445. 10.1016/j.vaccine.2006.02.020CrossRefPubMed

21.

Bennett AM, Phillpotts RJ, Perkins SD, Jacobs SC, Williamson ED: Gene gun mediated vaccination is superior to manual delivery for immunisation with DNA vaccines expressing protective antigens from Yersinia pestis or Venezuelan Equine Encephalitis virus. Vaccine 1999, 18: 588-96. 10.1016/S0264-410X(99)00317-5CrossRefPubMed

22.

Paessler S, Ni H, Petrakova O, Fayzulin RZ, Yun N, Anishchenko M, Weaver SC, Frolov I: Replication and Clearance of Venezuelan Equine Encephalitis Virus from the Brains of Animals Vaccinated with Chimeric SIN/VEE Viruses. J Virol 2006, 80: 2784-2796. 10.1128/JVI.80.6.2784-2796.2006PubMedCentralCrossRefPubMed

23.

Perkins SD, Williams AJ, O'Brien LM, Laws TR, Phillpotts RJ: CpG Used as an Adjuvant for an Adenovirus-Based Venezuelan Equine Encephalitis Virus Vaccine Increases the Immune Response to the Vector, But Not to the Transgene Product. Viral Immunology 2008, 21: 451. 10.1089/vim.2008.0052CrossRefPubMed

24.

O'Brien L, Perkins S, Williams A, Eastaugh L, Phelps A, Wu J, Phillpotts R: Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection. Journal of General Virology 2009, 90: 874-882. 10.1099/vir.0.006833-0CrossRefPubMed

25.

Capone S, Zampaglione I, Vitelli A, Pezzanera M, Kierstead L, Burns J, Ruggeri L, Arcuri M, Cappelletti M, Meola A, et al.: Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates. The Journal of Immunology 2006, 177: 7462-7471.CrossRefPubMed

26.

Zeng M, Xu Q, Elias M, Pichichero ME, Simpson LL, Smith LA: Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine. Vaccine 2007, 25: 7540-7548. 10.1016/j.vaccine.2007.08.035PubMedCentralCrossRefPubMed

27.

Aurisicchio L, Mennuni C, Giannetti P, Calvaruso F, Nuzzo M, Cipriani B, Palombo F, Monaci P, Ciliberto G, La Monica N: Immunogenicity and safety of a DNA prime/adenovirus boost vaccine against rhesus CEA in nonhuman primates. International Journal of Cancer 2007, 120: 2290-2300. 10.1002/ijc.22555CrossRef

28.

Ternette N, Tippler B, _berla K, Grunwald T: Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus. Vaccine 2007, 25: 7271-7279. 10.1016/j.vaccine.2007.07.025CrossRefPubMed

29.

Ko HJ, Ko SY, Kim YJ, Lee EG, Cho SN, Kang CY: Optimization of Codon Usage Enhances the Immunogenicity of a DNA Vaccine Encoding Mycobacterial Antigen Ag85B. Infect Immun 2005, 73: 5666-5674. 10.1128/IAI.73.9.5666-5674.2005PubMedCentralCrossRefPubMed

30.

Deml L, Bojak A, Steck S, Graf M, Wild J, Schirmbeck R, Wolf H, Wagner R: Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein. J Virol 2001, 75: 10991-11001. 10.1128/JVI.75.22.10991-11001.2001PubMedCentralCrossRefPubMed

31.

Graf M, Deml L, Wagner R: Codon-optimized genes that enable increased heterologous expression in mammalian cells and elicit efficient immune responses in mice after vaccination of naked DNA. Methods Mol Med 2004, 94: 197-210.PubMed

32.

Harari A, Bart PA, Stohr W, Tapia G, Garcia M, Medjitna-Rais E, Burnet S, Cellerai C, Erlwein O, Barber T, et al.: An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med 2008, 205: 63-77. 10.1084/jem.20071331PubMedCentralCrossRefPubMed

33.

McCormack S, Stohr W, Barber T, Bart PA, Harari A, Moog C, Ciuffreda D, Cellerai C, Cowen M, Gamboni R, et al.: EV02: A Phase I trial to compare the safety and immunogenicity of HIV DNA-C prime-NYVAC-C boost to NYVAC-C alone. Vaccine 2008, 26: 3162-3174. 10.1016/j.vaccine.2008.02.072CrossRefPubMed

34.

Gomez CE, Najera JL, Jimenez V, Bieler K, Wild J, Kostic L, Heidari S, Chen M, Frachette MJ, Pantaleo G, et al.: Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C. Vaccine 2007, 25: 1969-1992. 10.1016/j.vaccine.2006.11.051CrossRefPubMed

35.

Didierlaurent A, Ramirez JC, Gherardi M, Zimmerli SC, Graf M, Orbea HA, Pantaleo G, Wagner R, Esteban M, Kraehenbuhl JP, et al.: Attenuated poxviruses expressing a synthetic HIV protein stimulate HLA-A2-restricted cytotoxic T-cell responses. Vaccine 2004, 22: 3395-3403. 10.1016/j.vaccine.2004.02.025CrossRefPubMed

36.

Bennett AM, Elvin SJ, Wright AJ, Jones SM, Phillpotts RJ: An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitis virus vaccine. Vaccine 2000, 19: 337-47. 10.1016/S0264-410X(00)00123-7CrossRefPubMed

37.

Hart MK, Lind C, Bakken R, Robertson M, Tammariello R, Ludwig GV: Onset and duration of protective immunity to IA/IB and IE strains of Venezuelan equine encephalitis virus in vaccinated mice. Vaccine 2001, 20: 616-622. 10.1016/S0264-410X(01)00337-1CrossRefPubMed

38.

Phillpotts RJ, Wright A: TC-83 vaccine protects against airborne or subcutaneous challenge with heterologous mouse-virulent strains of Venezuelan equine encephalitis virus. Vaccine 1999, 17: 982-8. 10.1016/S0264-410X(98)00315-6CrossRefPubMed

39.

Phillpotts RJ: Venezuelan equine encephalitis virus complex-specific monoclonal antibody provides broad protection, in murine models, against airborne challenge with viruses from serogroups I, II and III. Virus Research 2006, 120: 107-112. 10.1016/j.virusres.2006.02.003CrossRefPubMed

40.

Phillpotts RJ, Jones LD, Howard SC: Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus. Vaccine 2002, 20: 1497-504. 10.1016/S0264-410X(01)00505-9CrossRefPubMed

41.

Yun NE, Peng BH, Bertke AS, Borisevich V, Smith JK, Smith JN, Poussard AL, Salazar M, Judy BM, Zacks MA, et al.: CD4+ T cells provide protection against acute lethal encephalitis caused by Venezuelan equine encephalitis virus. Vaccine 2009, 27: 4064-4073. 10.1016/j.vaccine.2009.04.015PubMedCentralCrossRefPubMed

42.

Paessler S, Yun NE, Judy BM, Dziuba N, Zacks MA, Grund AH, Frolov I, Campbell GA, Weaver SC, Estes DM: Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection. Virology 2007, 367: 307-323. 10.1016/j.virol.2007.05.041PubMedCentralCrossRefPubMed

43.

Draper SJ, Moore AC, Goodman AL, Long CA, Holder AA, Gilbert SC, Hill F, Hill AVS: Effective induction of high-titer antibodies by viral vector vaccines. Nat Med 2008, 14: 819-821. 10.1038/nm.1850CrossRefPubMed

44.

Li S, Locke E, Bruder J, Clarke D, Doolan DL, Havenga MJE, Hill AVS, Liljestrom P, Monath TP, Naim HY, et al.: Viral vectors for malaria vaccine development. Vaccine 2007, 25: 2567-2574. 10.1016/j.vaccine.2006.07.035CrossRefPubMed

45.

Toro H, Tang Dc, Suarez DL, Zhang J, Shi Z: Protection of chickens against avian influenza with non-replicating adenovirus-vectored vaccine. Vaccine 2008, 26: 2640-2646. 10.1016/j.vaccine.2008.02.056PubMedCentralCrossRefPubMed

46.

Barouch DH, Pau MG, Custers JHHV, Koudstaal W, Kostense S, Havenga MJE, Truitt DM, Sumida SM, Kishko MG, Arthur JC, et al.: Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. Journal of Immunology 2004, 172: 6290-6297.CrossRef

47.

Phillpotts RJ, Brooks TJ, Cox CS: A simple device for the exposure of animals to infectious microorganisms by the airborne route. Epidemiol Infect 1997, 118: 71-5. 10.1017/S0950268896007157PubMedCentralCrossRefPubMed

48.

Guyton AC: Measurement of the respiratory volume of laboratory animals. Am J Physiol 1947, 150: 70-77.PubMed

49.

Wright AJ, Phillpotts RJ: Humane endpoints are an objective measure of morbidity in Venezuelan encephalomyelitis virus infection of mice. Arch Virol 1998, 143: 1155-62. 10.1007/s007050050363CrossRefPubMed

Title: Improved Efficacy of a Gene Optimised Adenovirus-based Vaccine for Venezuelan Equine Encephalitis Virus
Authors: Amanda J Williams
Lyn M O'Brien
Robert J Phillpotts
Stuart D Perkins
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2009
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/1743-422X-6-118

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2009

Pathogenesis of swine influenza virus (Thai isolates) in weanling pigs: an experimental trial

Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

Conserved peptides within the E2 region of Hepatitis C virus induce humoral and cellular responses in goats

Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo

Detection of hepatitis E virus in wild boars of rural and urban regions in Germany and whole genome characterization of an endemic strain

Expression of Ebolavirus glycoprotein on the target cells enhances viral entry

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials