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Citation: Huadong Wang, Yanfeng Yao, Chaoyang Huang, Quanjiao Chen, Jianjun Chen, Ze Chen. Immunization with Cytomegalovirus Envelope Glycoprotein M and Glycoprotein N DNA Vaccines can Provide Mice with Complete Protection against a Lethal Murine Cytomegalovirus Challenge [J].VIROLOGICA SINICA, 2013, 28(3) : 174-182.  http://dx.doi.org/10.1007/s12250-013-3330-9

Immunization with Cytomegalovirus Envelope Glycoprotein M and Glycoprotein N DNA Vaccines can Provide Mice with Complete Protection against a Lethal Murine Cytomegalovirus Challenge

  • Corresponding author: Ze Chen, chenze2005@263.net
  • Received Date: 05 April 2013
    Accepted Date: 20 May 2013
    Available online: 01 June 2013
  • Human cytomegalovirus virions contain three major glycoprotein complexes (gC I, II, III), all of which are required for CMV infectivity. These complexes also represent major antigenic targets for anti-viral immune responses. The gC II complex consists of two glycoproteins, gM and gN. In the current study, DNA vaccines expressing the murine cytomegalovirus (MCMV) homologs of the gM and gN proteins were evaluated for protection against lethal MCMV infection in a mouse model. Humoral and cellular immune responses, spleen viral titers, and mice survival and body-weight changes were examined. The results showed that immunization with gM or gN DNA vaccine alone was not able to offer good protection, whereas co-immunization with both gM and gN induced an effective neutralizing antibody response and cellular immune response, and provided mice with complete protection against a lethal MCMV challenge. This study provides the first in vivo evidence that the gC II (gM-gN) complex may be able to serve as a protective subunit antigen for future HCMV vaccine development.

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    1. Aihara H, and Miyazaki J. 1998. Gene transfer into muscle by electroporation in vivo. Nat Biotechnol, 16: 867-870.
        doi: 10.1038/nbt0998-867

    2. Arvin A M, Fast P, Myers M, Plotkin S, and Rabinovich R. 2004. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis, 39: 233-239.
        doi: 10.1086/421999

    3. Boeckh M, and Geballe A P. 2011. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest, 121: 1673-1680.
        doi: 10.1172/JCI45449

    4. Britt W J, and Mach M. 1996. Human cytomegalovirus glycoproteins. Intervirology, 39: 401-412.
        doi: 10.1159/000150510

    5. Britt W J, and Boppana S. 2004. Human cytomegalovirus virion proteins. Hum Immunol, 65: 395-402.
        doi: 10.1016/j.humimm.2004.02.008

    6. Brune W, Hengel H, and Koszinowski U H. 2001. A mouse model for cytomegalovirus infection. Curr Protoc Immunol, Chapter 19: Unit 19 17.

    7. Chen J J, Huang S P, and Chen Z. 2010. Human cellular protein nucleoporin hNup98 interacts with influenza A virus NS2/nuclear export protein and overexpression of its GLFG repeat domain can inhibit virus propagation. J Gen Virol, 91: 2474-2484.
        doi: 10.1099/vir.0.022681-0

    8. Geoffroy F, Moachon N, Rodwell J, and Quash G A. 1996. Murine cytomegalovirus inactivated by sodium periodate is innocuous and immunogenic in mice and protects them against death and infection. Vaccine, 14: 1686-1694.
        doi: 10.1016/S0264-410X(96)00116-8

    9. Griffiths P D. 2002. The 2001 Garrod lecture. The treatment of cytomegalovirus infection. J Antimicrob Chemother, 49: 243-253.
        doi: 10.1093/jac/49.2.243

    10. Hobom U, Brune W, Messerle M, Hahn G, and Koszinowski U H. 2000. Fast screening procedures for random transposon libraries of cloned herpesvirus genomes: mutational analysis of human cytomegalovirus envelope glycoprotein genes. J Virol, 74: 7720-7729.
        doi: 10.1128/JVI.74.17.7720-7729.2000

    11. Jons A, Dijkstra J M, and Mettenleiter T C. 1998. Glycoproteins M and N of pseudorabies virus form a disulfide-linked complex. J Virol, 72: 550-557.

    12. Khanna R, and Diamond D J. 2006. Human cytomegalovirus vaccine: time to look for alternative options. Trends Mol Med, 12: 26-33.
        doi: 10.1016/j.molmed.2005.11.006

    13. Krzyzaniak M, Mach M, and Britt W J. 2007. The cytoplasmic tail of glycoprotein M (gpUL100) expresses trafficking signals required for human cytomegalovirus assembly and replication. J Virol, 81: 10316-10328.
        doi: 10.1128/JVI.00375-07

    14. Lazzarotto T, and Lanari M. 2011. Why is cytomegalovirus the most frequent cause of congenital infection? Expert Rev Anti Infect Ther, 9: 841-843.
        doi: 10.1586/eri.11.109

    15. Loomis R J, Lilja A E, Monroe J, Balabanis K A, Brito L, Palladino G, Franti M, Mandl C W, Barnett S W, and Mason P W. 2012. Vectored co-delivery of human cytomegalovirus gH and gL proteins elicits potent complement-independent neutralizing antibodies. Vaccine, 31(6):919-926.

    16. Mach M, Kropff B, Dal Monte P, and Britt W. 2000. Complex formation by human cytomegalovirus glycoproteins M (gpUL100) and N (gpUL73). J Virol, 74: 11881-11892.
        doi: 10.1128/JVI.74.24.11881-11892.2000

    17. Mach M, Kropff B, Kryzaniak M, and Britt W. 2005. Complex formation by glycoproteins M and N of human cytomegalovirus: structural and functional aspects. J Virol, 79: 2160-2170.
        doi: 10.1128/JVI.79.4.2160-2170.2005

    18. Mach M, Osinski K, Kropff B, Schloetzer-Schrehardt U, Krzyzaniak M, and Britt W. 2007. The carboxy-terminal domain of glycoprotein N of human cytomegalovirus is required for virion morphogenesis. J Virol, 81: 5212-5224.
        doi: 10.1128/JVI.01463-06

    19. Manley K, Anderson J, Yang F, Szustakowski J, Oakeley E J, Compton T, and Feire A L. 2011. Human cytomegalovirus escapes a naturally occurring neutralizing antibody by incorporating it into assembling virions. Cell Host & Microbe, 10: 197-209.

    20. Pass R F, Zhang C P, Evans A, Simpson T, Andrews W, Huang M L, Corey L, Hill J, Davis E, Flanigan C, and Cloud G. 2009. Vaccine prevention of maternal cytomegalovirus infection. New England Journal of Medicine, 360: 1191-1199.
        doi: 10.1056/NEJMoa0804749

    21. Qureshi M H, Garvy B A, Pomeroy C, Inayat M S, and Oakley O R. 2005. A murine model of dual infection with cytomegalovirus and Pneumocystis carinii: Effects of virus-induced immunomodulation on disease progression. Virus Research, 114: 35-44.
        doi: 10.1016/j.virusres.2005.05.008

    22. Scalzo A A, Forbes C A, Davis-Poynter N J, Farrell H E, and Lyons P A. 1995. DNA sequence and transcriptional analysis of the glycoprotein M gene of murine cytomegalovirus. J Gen Virol, 76 (Pt 11): 2895-2901.

    23. Schleiss M R, and Heineman T C. 2005. Progress toward an elusive goal: current status of cytomegalovirus vaccines. Expert Rev Vaccines, 4: 381-406.
        doi: 10.1586/14760584.4.3.381

    24. Shen S, Wang S, Britt W J, and Lu S. 2007. DNA vaccines expressing glycoprotein complex Ⅱ antigens gM and gN elicited neutralizing antibodies against multiple human cytomegalovirus (HCMV) isolates. Vaccine, 25: 3319-3327.
        doi: 10.1016/j.vaccine.2007.01.011

    25. Shimamura M, Mach M, and Britt W J. 2006. Human cytomegalovirus infection elicits a glycoprotein M (gM)/gN-specific virus-neutralizing antibody response. J Virol, 80: 4591-4600.
        doi: 10.1128/JVI.80.9.4591-4600.2006

    26. Sung H, and Schleiss M R. 2010. Update on the current status of cytomegalovirus vaccines. Expert Rev Vaccines, 9: 1303-1314.
        doi: 10.1586/erv.10.125

    27. Tandon R, and Mocarski E S. 2012. Viral and host control of cytomegalovirus maturation. Trends Microbiol, 20: 392-401.
        doi: 10.1016/j.tim.2012.04.008

    28. Wang D, and Shenk T. 2005. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A, 102: 18153-18158.
        doi: 10.1073/pnas.0509201102

    29. Zhong J, and Khanna R. 2007. Vaccine strategies against human cytomegalovirus infection. Expert Rev Anti Infect Ther, 5: 449-459.
        doi: 10.1586/14787210.5.3.449

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    Immunization with Cytomegalovirus Envelope Glycoprotein M and Glycoprotein N DNA Vaccines can Provide Mice with Complete Protection against a Lethal Murine Cytomegalovirus Challenge

      Corresponding author: Ze Chen, chenze2005@263.net
    • State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    • College of Life Science, Hunan Normal University, Changsha 410081, China
    • Shanghai Institute of Biological Products, Shanghai 200052, China
    • Graduate University of Chinese Academy of Sciences, Beijing 100049, China

    Abstract: Human cytomegalovirus virions contain three major glycoprotein complexes (gC I, II, III), all of which are required for CMV infectivity. These complexes also represent major antigenic targets for anti-viral immune responses. The gC II complex consists of two glycoproteins, gM and gN. In the current study, DNA vaccines expressing the murine cytomegalovirus (MCMV) homologs of the gM and gN proteins were evaluated for protection against lethal MCMV infection in a mouse model. Humoral and cellular immune responses, spleen viral titers, and mice survival and body-weight changes were examined. The results showed that immunization with gM or gN DNA vaccine alone was not able to offer good protection, whereas co-immunization with both gM and gN induced an effective neutralizing antibody response and cellular immune response, and provided mice with complete protection against a lethal MCMV challenge. This study provides the first in vivo evidence that the gC II (gM-gN) complex may be able to serve as a protective subunit antigen for future HCMV vaccine development.