Expression of the human cytomegalovirus pentamer complex for vaccine use in a CHO system

Biotechnology and Bioengineering

Volumn 112, Issue 12, 2015, Pages 2505-2515

  Hofmann, Irmgard ^a   Wen, Yingxia ^b   Ciferri, Claudio ^b   Schulze, Axel ^a   Fühner, Viola ^a   Leong, Megan ^a   Gerber, Andrea ^a   Gerrein, Rachel ^b   Nandi, Avishek ^b   Lilja, Anders E ^b   Carfi, Andrea ^b   Laux, Holger ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b Novartis Vaccines Cambridge   (United States)

Author keywords

CHO; HCMV Pentamer; HCMV vaccine; IRES; Mammalian expression system

Indexed keywords

ANTIBODIES; CELL CULTURE; CLONE CELLS; MAMMALS; MANUFACTURE; VACCINES;

CHO; EXPRESSION SYSTEM; FED-BATCH CULTURES; HUMAN CYTOMEGALOVIRUS; IRES; LARGE SCALE PRODUCTIONS; NEUTRALIZING ANTIBODIES; PENTAMERS;

BATCH CELL CULTURE;

CYTOMEGALOVIRUS VACCINE; EPITOPE; HUMAN CYTOMEGALOVIRUS PENTAMER COMPLEX VACCINE; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG; RECOMBINANT VACCINE; SUBUNIT VACCINE; VIRUS ANTIBODY; VIRUS PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIBODY TITER; ARTICLE; BIOREACTOR; CELL SELECTION; CHO CELL LINE; CLONE; CONTROLLED STUDY; FEASIBILITY STUDY; FED BATCH CULTURE; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION SYSTEM; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IMMUNE RESPONSE; IMMUNOGENICITY; LARGE SCALE PRODUCTION; MOUSE; NONHUMAN; SCALE UP; ANIMAL; BLOOD; CRICETULUS; CYTOMEGALOVIRUS; GENE EXPRESSION; GENETICS; IMMUNOLOGY; METABOLISM; PROTEIN MULTIMERIZATION;

ANIMALS; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; CHO CELLS; CRICETULUS; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS VACCINES; GENE EXPRESSION; MICE; PROTEIN MULTIMERIZATION; VACCINES, SUBUNIT; VACCINES, SYNTHETIC; VIRAL PROTEINS;

EID: 84946484765     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.25670     Document Type: Article

References (39)

1. Birch JR, Racher AJ. 2006. Antibody production. Adv Drug Deliv Rev 58(5-6):671-685.
2. Britt W. 2008. Manifestations of human cytomegalovirus infection: Proposed mechanisms of acute and chronic disease. Curr Top Microbiol Immunol 325:417-470.
3. Ciferri C, Chandramouli S, Donnarumma D, Nikitin PA, Cianfrocco MA, Gerrein R, Feire AL, Barnett SW, Lilja AE, Rappuoli R, Norais N, Settembre EC, Carfi A. 2015. Structural and biochemical studies of HCMV gH/gL/gO and Pentamer reveal mutually exclusive cell entry complexes. Proc Natl Acad Sci USA 112(6):1767-1772.
4. Datta P, Linhardt RJ, Sharfstein ST. 2013. An 'omics approach towards CHO cell engineering. Biotechnol Bioeng 110(5):1255-1271.
5. De Jesus M, Wurm FM. 2011. Manufacturing recombinant proteins in kg-ton quantities using animal cells in bioreactors. Eur J Pharm Biopharm 78(2):184-188.
6. de Sousa Abreu R, Penalva LO, Marcotte EM, Vogel C. 2009. Global signatures of protein and mRNA expression levels. Mol Biosyst 5(12):1512-1526.
7. Dorai H, Corisdeo S, Ellis D, Kinney C, Chomo M, Hawley-Nelson P, Moore G, Betenbaugh MJ, Ganguly S. 2012. Early prediction of instability of chinese hamster ovary cell lines expressing recombinant antibodies and antibody-fusion proteins. Biotechnol Bioeng 109(4):1016-1030.
8. Fouts AE, Chan P, Stephan JP, Vandlen R, Feierbach B. 2012. Antibodies against the gH/gL/UL128/UL130/UL131 complex comprise the majority of the anti-cytomegalovirus (anti-CMV) neutralizing antibody response in CMV hyperimmune globulin. J Virol 86(13):7444-7447.
9. Freed DC, Tang Q, Tang A, Li F, He X, Huang Z, Meng W, Xia L, Finnefrock AC, Durr E, Espeseth AS, Casimiro DR, Zhang N, Shiver JW, Wang D, An Z, Fu TM. 2013. Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine. Proc Natl Acad Sci USA 110(51):E4997-E5005.
10. Fu TM, Wang D, Freed DC, Tang A, Li F, He X, Cole S, Dubey S, Finnefrock AC, ter Meulen J, Shiver JW, Casimiro DR. 2012. Restoration of viral epithelial tropism improves immunogenicity in rabbits and rhesus macaques for a whole virion vaccine of human cytomegalovirus. Vaccine 30(52):7469-7474.
11. Ho SC, Bardor M, Feng H, Mariati, Tong YW, Song Z, Yap MG, Yang Y. 2012. IRES-mediated Tricistronic vectors for enhancing generation of high monoclonal antibody expressing CHO cell lines. J Biotechnol 157(1):130-139.
12. Huang Y-M, Hu W, Rustandi E, Chang K, Yusuf-Makagiansar H, Ryll T. 2010. Maximizing productivity of CHO cell-based fed-batch culture using chemically defined media conditions and typical manufacturing equipment. Biotechnol Prog 26(5):1400-1410.
13. Jayapal KP WK, Hu WS, Yap MGS. 2007. Recombinant protein therapeutics from CHO cells-20 years and counting. Chem Eng Prog 103(10):40.
14. Kabanova A, Perez L, Lilleri D, Marcandalli J, Agatic G, Becattini S, Preite S, Fuschillo D, Percivalle E, Sallusto F, Gerna G, Corti D, Lanzavecchia A. 2014. Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies. Proc Natl Acad Sci USA 111(50):17965-17970.
15. Kaloff CR, Haas IG. 1995. Coordination of immunoglobulin chain folding and immunoglobulin chain assembly is essential for the formation of functional IgG. Immunity 2(6):629-637.
16. Kalwy S, Rance J, Young R. 2006. Toward more efficient protein expression: keep the message simple. Mol Biotechnol 34(2):151-156.
17. Laux H. 2014. Industry perspective on Chinese hamster ovary cell 'omics'. Pharm Bioproc 2(5):377-381.
18. Lee JC, Wu TY, Huang CF, Yang FM, Shih SR, Hsu JT. 2005. High-efficiency protein expression mediated by enterovirus 71 internal ribosome entry site. Biotechnol Bioeng 90(5):656-662.
19. Lewis NE, Liu X, Li Y, Nagarajan H, Yerganian G, O'Brien E, Bordbar A, Roth AM, Rosenbloom J, Bian C, Xie M, Chen W, Li N, Baycin-Hizal D, Latif H, Forster J, Betenbaugh MJ, Famili I, Xu X, Wang J, Palsson BO. 2013. Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome. Nat Biotechnol 31(8):759-765.
20. Lilja AE, Mason PW. 2012. The next generation recombinant human cytomegalovirus vaccine candidates-beyond gB. Vaccine 30(49):6980-6990.
21. Loughney JW, Rustandi RR, Wang D, Troutman MC, Dick LW, Jr., Li G, Liu Z, Li F, Freed DC, Price CE, Hoang VM, Culp TD, DePhillips PA, Fu TM, Ha S. 2015. Soluble human cytomegalovirus gH/gL/pUL 128-131 pentameric complex, but not gH/gL, inhibits viral entry to epithelial cells and presents dominant native neutralizing epitopes. J Biol Chem.
22. Macagno A, Bernasconi NL, Vanzetta F, Dander E, Sarasini A, Revello MG, Gerna G, Sallusto F, Lanzavecchia A. 2010. Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex. J Virol 84(2):1005-1013.
23. Maier T, Guell M, Serrano L. 2009. Correlation of mRNA and protein in complex biological samples. FEBS Lett 583(24):3966-3973.
24. Montano RF, Morrison SL. 2002. Influence of the isotype of the light chain on the properties of IgG. J Immunol 168(1):224-231.
25. Olal D, Kuehne AI, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM, Jr, Saphire EO. 2012. Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus. J Virol 86(5):2809-2816.
26. Puck TT, Cieciura SJ, Robinson A. 1958. Genetics of somatic mammalian cells. III. Long-term cultivation of euploid cells from human and animal subjects. J Exp Med 108(6):945-956.
27. Schlatter S, Stansfield SH, Dinnis DM, Racher AJ, Birch JR, James DC. 2005. On the optimal ratio of heavy to light chain genes for efficient recombinant antibody production by CHO cells. Biotechnol Prog 21(1):122-133.
28. Thompson SR, Sarnow P. 2003. Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved. Virology 315(1):259-266.
29. Tjio JH, Puck TT. 1958. Genetics of somatic mammalian cells. II. Chromosomal constitution of cells in tissue culture. J Exp Med 108(2):259-268.
30. Walsh G. 2010. Biopharmaceutical benchmarks 2010. Nat Biotech 28(9):917-924.
31. Walsh G. 2014. Biopharmaceutical benchmarks 2014. Nat Biotechnol 32(10):992-1000.
32. Wang D, Shenk T. 2005. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci USA 102(50):18153-18158.
33. Watson PJ, Fairall L, Santos GM, Schwabe JW. 2012. Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature 481(7381):335-340.
34. Wen Y, Monroe J, Linton C, Archer J, Beard CW, Barnett SW, Palladino G, Mason PW, Carfi A, Lilja AE. 2014. Human cytomegalovirus gH/gL/UL128/UL130/UL131A complex elicits potently neutralizing antibodies in mice. Vaccine 32(30):3796-3804.
35. Wurm FM. 2004. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotech 22(11):1393-1398.
36. Wurm FM, Hacker D. 2011. First CHO genome. Nat Biotechnol 29(8):718-720.
37. Wussow F, Chiuppesi F, Martinez J, Campo J, Johnson E, Flechsig C, Newell M, Tran E, Ortiz J, La Rosa C, Herrmann A, Longmate J, Chakraborty R, Barry PA, Diamond DJ. 2014. Human cytomegalovirus vaccine based on the envelope gH/gL pentamer complex. PLoS Pathog 10(11):e004524.
38. Wussow F, Yue Y, Martinez J, Deere JD, Longmate J, Herrmann A, Barry PA, Diamond DJ. 2013. A vaccine based on the rhesus cytomegalovirus UL128 complex induces broadly neutralizing antibodies in rhesus macaques. J Virol 87(3):1322-1332.
39. Zhou M, Yu Q, Wechsler A, Ryckman BJ. 2013. Comparative analysis of gO isoforms reveals that strains of human cytomegalovirus differ in the ratio of gH/gL/gO and gH/gL/UL 128-131 in the virion envelope. J Virol 87(17):9680-9690.