Chapter 25 : Vector-Mediated Antibody Expression

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The holy grail of human immunodeficiency virus (HIV) vaccine development is an immunogen that elicits antibodies that neutralize field strains of the virus. In recent years, we have gained tremendous insights into the structure and function of the HIV envelope glycoprotein, but limited progress has been made in designing such immunogens. These sobering observations underscore the tremendous hurdles that must be overcome to develop an effective HIV vaccine ( ). Foremost among these hurdles is the inability to induce antibodies that neutralize a wide array of HIV field isolates. Such antibodies are rare, and, until recently, only a handful of these antibodies had been isolated ( ). Over the past few years, a much larger number of HIV antibodies have been identified that have a much broader range of neutralization and are orders of magnitude more potent than the previously identified group ( ). These antibodies were isolated from the high-throughput screening of sera from HIV-1-infected individuals and categorized as “elite neutralizers” based on their neutralization breadth and potency ( ). Extensive sequence analysis of these potent, broadly neutralizing antibodies revealed that high levels of somatic mutations were involved to generate the mature antibody ( ). Furthermore, the maturation may have involved repeated rounds of antibody selection through HIV antigen interaction, a process that may not be possible to duplicate from a traditional HIV protein subunit or viral vector vaccine.

Citation: Schnepp B, Johnson P. 2015. Vector-Mediated Antibody Expression, p 427-440. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0016-2014
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Figure 1

Immunoprophylaxis by antibody gene transfer. Passive immunization involves intravenous delivery of purified antibodies to engender the host with short-lived immunity in serum and mucosa. In contrast, vector-mediated antibody gene transfer uses a viral vector to deliver the antibody to the host via intramuscular injection. The antibody is produced endogenously in the muscle and secreted into the circulatory system and mucosa providing long-term protection from infection. (Reprinted from reference [Schnepp BC, Johnson PR. 2014. Adeno-associated virus delivery of broadly neutralizing antibodies. 205–256] with permission.)

Citation: Schnepp B, Johnson P. 2015. Vector-Mediated Antibody Expression, p 427-440. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0016-2014
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Figure 2

rAAV vectors for antibody gene transfer. The wild-type AAV (wtAAV) genome consists of the and genes flanked by inverted terminal repeats (ITRs). For rAAV vectors, the and genes are removed and replaced by an antibody expression cassette flanked by ITRs, which are necessary for rAAV vector genome replication and packaging. Immunoadhesins contain the antibody variable domains (VL, variable light; VH, variable heavy) usually joined by a flexible protein linker. The variable domains are connected to the hinge and constant heavy-chain domains (CH2 and CH3). The immunoadhesins can form dimers through disulfide bonding in the hinge region. Full antibodies can be expressed by using either a dual promoter or single-promoter system. For dual promoter expression, the antibody heavy and light chains are each expressed separately from their own promoter. For the single promoter system, the heavy and light chains are expressed as a single polypeptide separated by the foot-and-mouth-disease virus 2A peptide (FMDV-2A). The FMDV-2A peptide can undergo self-cleavage to give rise to separate heavy and light chains.

Citation: Schnepp B, Johnson P. 2015. Vector-Mediated Antibody Expression, p 427-440. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0016-2014
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1. Desrosiers R . 2004. Prospects for an AIDS vaccine. Nat Med 10 : 221 223.[PubMed] [CrossRef]
2. Fauci AS,, Johnston MI,, Dieffenbach CW,, Burton DR,, Hammer SM,, Hoxie JA,, Martin M,, Overbaugh J,, Watkins DI,, Mahmoud A,, Greene WC . 2008. HIV vaccine research: the way forward. Science 321 : 530 532.[PubMed] [CrossRef]
3. Morgan C,, Marthas M,, Miller C,, Duerr A,, Cheng-Mayer C,, Desrosiers R,, Flores J,, Haigwood N,, Hu SL,, Johnson RP,, Lifson J,, Montefiori D,, Moore J,, Robert-Guroff M,, Robinson H,, Self S,, Corey L . 2008. The use of nonhuman primate models in HIV vaccine development. PLoS Med 5 : e173. doi:10.1371/journal.pmed.0050173. [PubMed] [CrossRef]
4. Walker B,, Burton D . 2008. Toward an AIDS vaccine. Science 320 : 760 764.[PubMed] [CrossRef]
5. Watkins DI . 2008. Basic HIV Vaccine development. Top HIV Med 16 : 7 8.[PubMed]
6. Burton DR,, Pyati J,, Koduri R,, Sharp SJ,, Thornton GB,, Parren PW,, Sawyer LS,, Hendry RM,, Dunlop N,, Nara PL , , et al . 1994. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266 : 1024 1027.[PubMed] [CrossRef]
7. Muster T,, Steindl F,, Purtscher M,, Trkola A,, Klima A,, Himmler G,, Ruker F,, Katinger H . 1993. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67 : 6642 6647.[PubMed]
8. Trkola A,, Purtscher M,, Muster T,, Ballaun C,, Buchacher A,, Sullivan N,, Srinivasan K,, Sodroski J,, Moore JP,, Katinger H . 1996. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 70 : 1100 1108.[PubMed]
9. Zwick MB,, Labrijn AF,, Wang M,, Spenlehauer C,, Saphire EO,, Binley JM,, Moore JP,, Stiegler G,, Katinger H,, Burton DR,, Parren PW . 2001. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol 75 : 10892 10905.[PubMed] [CrossRef]
10. Burton DR,, Poignard P,, Stanfield RL,, Wilson IA . 2012. Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science 337 : 183 186.[PubMed] [CrossRef]
11. Walker LM,, Huber M,, Doores KJ,, Falkowska E,, Pejchal R,, Julien JP,, Wang SK,, Ramos A,, Chan-Hui PY,, Moyle M,, Mitcham JL,, Hammond PW,, Olsen OA,, Phung P,, Fling S,, Wong CH,, Phogat S,, Wrin T,, Simek MD,, Koff WC,, Wilson IA,, Burton DR,, Poignard P . 2011. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477 : 466 470.[PubMed] [CrossRef]
12. Walker LM,, Phogat SK,, Chan-Hui PY,, Wagner D,, Phung P,, Goss JL,, Wrin T,, Simek MD,, Fling S,, Mitcham JL,, Lehrman JK,, Priddy FH,, Olsen OA,, Frey SM,, Hammond PW,, Kaminsky S,, Zamb T,, Moyle M,, Koff WC,, Poignard P,, Burton DR . 2009. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326 : 285 289.[PubMed] [CrossRef]
13. Wu X,, Yang ZY,, Li Y,, Hogerkorp CM,, Schief WR,, Seaman MS,, Zhou T,, Schmidt SD,, Wu L,, Xu L,, Longo NS,, McKee K,, O’Dell S,, Louder MK,, Wycuff DL,, Feng Y,, Nason M,, Doria-Rose N,, Connors M,, Kwong PD,, Roederer M,, Wyatt RT,, Nabel GJ,, Mascola JR . 2010. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329 : 856 861.[PubMed] [CrossRef]
14. Simek MD,, Rida W,, Priddy FH,, Pung P,, Carrow E,, Laufer DS,, Lehrman JK,, Boaz M,, Tarragona-Fiol T,, Miiro G,, Birungi J,, Pozniak A,, McPhee DA,, Manigart O,, Karita E,, Inwoley A,, Jaoko W,, Dehovitz J,, Bekker LG,, Pitisuttithum P,, Paris R,, Walker LM,, Poignard P,, Wrin T,, Fast PE,, Burton DR,, Koff WC . 2009. Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol 83 : 7337 7348.[PubMed] [CrossRef]
15. Baba TW,, Liska V,, Hofmann-Lehmann R,, Vlasak J,, Xu W,, Ayehunie S,, Cavacini LA,, Posner MR,, Katinger H,, Stiegler G,, Bernacky BJ,, Rizvi TA,, Schmidt R,, Hill LR,, Keeling ME,, Lu Y,, Wright JE,, Chou TC,, Ruprecht RM . 2000. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med 6 : 200 206.[PubMed] [CrossRef]
16. Mascola JR,, Stiegler G,, VanCott TC,, Katinger H,, Carpenter CB,, Hanson CE,, Beary H,, Hayes D,, Frankel SS,, Birx DL,, Lewis MG . 2000. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 6 : 207 210.[PubMed] [CrossRef]
17. Parren PW,, Marx PA,, Hessell AJ,, Luckay A,, Harouse J,, Cheng-Mayer C,, Moore J,, Burton DR . 2001. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol 75 : 8340 8347.[PubMed] [CrossRef]
18. Hessell AJ,, Poignard P,, Hunter M,, Hangartner L,, Tehrani DM,, Bleeker WK,, Parren PW,, Marx PA,, Burton DR . 2009. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med 15 : 951 954.[PubMed] [CrossRef]
19. Hessell AJ,, Rakasz EG,, Poignard P,, Hangartner L,, Landucci G,, Forthal DN,, Koff WC,, Watkins DI,, Burton DR . 2009. Broadly neutralizing human anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers. PLoS Pathog 5 : e1000433. doi:10.1371/journal.ppat.1000433. [PubMed] [CrossRef]
20. Willey R,, Nason MC,, Nishimura Y,, Follmann DA,, Martin MA . 2010. Neutralizing antibody titers conferring protection to macaques from a simian/human immunodeficiency virus challenge using the TZM-bl assay. AIDS Res Hum Retroviruses 26 : 89 98.[PubMed] [CrossRef]
21. Berkhout B,, Sanders RW . 2012. Gene therapy as a vaccine for HIV-1. Expert Opin Biol Ther 12 : 1315 1321.[PubMed] [CrossRef]
22. Johnson PR,, Schnepp BC,, Zhang J,, Connell MJ,, Greene SM,, Yuste E,, Desrosiers RC,, Clark KR . 2009. Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys. Nat Med 15 : 901 906.[PubMed] [CrossRef]
23. Buchbinder SP,, Mehrotra DV,, Duerr A,, Fitzgerald DW,, Mogg R,, Li D,, Gilbert PB,, Lama JR,, Marmor M,, Del Rio C,, McElrath MJ,, Casimiro DR,, Gottesdiener KM,, Chodakewitz JA,, Corey L,, Robertson MN . 2008. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372 : 1881 1893.[PubMed] [CrossRef]
24. Flynn NM,, Forthal DN,, Harro CD,, Judson FN,, Mayer KH,, Para MF . 2005. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 191 : 654 665.[PubMed] [CrossRef]
25. McElrath MJ,, De Rosa SC,, Moodie Z,, Dubey S,, Kierstead L,, Janes H,, Defawe OD,, Carter DK,, Hural J,, Akondy R,, Buchbinder SP,, Robertson MN,, Mehrotra DV,, Self SG,, Corey L,, Shiver JW,, Casimiro DR . 2008. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372 : 1894 1905.[PubMed] [CrossRef]
26. Pitisuttithum P,, Gilbert P,, Gurwith M,, Heyward W,, Martin M,, van Griensven F,, Hu D,, Tappero JW,, Choopanya K . 2006. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 194 : 1661 1671.[PubMed] [CrossRef]
27. Rerks-Ngarm S,, Pitisuttithum P,, Nitayaphan S,, Kaewkungwal J,, Chiu J,, Paris R,, Premsri N,, Namwat C,, de Souza M,, Adams E,, Benenson M,, Gurunathan S,, Tartaglia J,, McNeil JG,, Francis DP,, Stablein D,, Birx DL,, Chunsuttiwat S,, Khamboonruang C,, Thongcharoen P,, Robb ML,, Michael NL,, Kunasol P,, Kim JH . 2009. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361 : 2209 2220.[PubMed] [CrossRef]
28. Haynes BF,, Gilbert PB,, McElrath MJ,, Zolla-Pazner S,, Tomaras GD,, Alam SM,, Evans DT,, Montefiori DC,, Karnasuta C,, Sutthent R,, Liao HX,, DeVico AL,, Lewis GK,, Williams C,, Pinter A,, Fong Y,, Janes H,, DeCamp A,, Huang Y,, Rao M,, Billings E,, Karasavvas N,, Robb ML,, Ngauy V,, de Souza MS,, Paris R,, Ferrari G,, Bailer RT,, Soderberg KA,, Andrews C,, Berman PW,, Frahm N,, De Rosa SC,, Alpert MD,, Yates NL,, Shen X,, Koup RA,, Pitisuttithum P,, Kaewkungwal J,, Nitayaphan S,, Rerks-Ngarm S,, Michael NL,, Kim JH . 2012. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 366 : 1275 1286.[PubMed] [CrossRef]
29. Hammer SM,, Sobieszczyk ME,, Janes H,, Karuna ST,, Mulligan MJ,, Grove D,, Koblin BA,, Buchbinder SP,, Keefer MC,, Tomaras GD,, Frahm N,, Hural J,, Anude C,, Graham BS,, Enama ME,, Adams E,, DeJesus E,, Novak RM,, Frank I,, Bentley C,, Ramirez S,, Fu R,, Koup RA,, Mascola JR,, Nabel GJ,, Montefiori DC,, Kublin J,, McElrath MJ,, Corey L,, Gilbert PB . 2013. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 369 : 2083 2092.[PubMed] [CrossRef]
30. Huang J,, Ofek G,, Laub L,, Louder MK,, Doria-Rose NA,, Longo NS,, Imamichi H,, Bailer RT,, Chakrabarti B,, Sharma SK,, Alam SM,, Wang T,, Yang Y,, Zhang B,, Migueles SA,, Wyatt R,, Haynes BF,, Kwong PD,, Mascola JR,, Connors M . 2012. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491 : 406 412.[PubMed] [CrossRef]
31. Scheid JF,, Mouquet H,, Ueberheide B,, Diskin R,, Klein F,, Oliveira TY,, Pietzsch J,, Fenyo D,, Abadir A,, Velinzon K,, Hurley A,, Myung S,, Boulad F,, Poignard P,, Burton DR,, Pereyra F,, Ho DD,, Walker BD,, Seaman MS,, Bjorkman PJ,, Chait BT,, Nussenzweig MC . 2011. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333 : 1633 1637.[PubMed] [CrossRef]
32. Zhou T,, Georgiev I,, Wu X,, Yang ZY,, Dai K,, Finzi A,, Kwon YD,, Scheid JF,, Shi W,, Xu L,, Yang Y,, Zhu J,, Nussenzweig MC,, Sodroski J,, Shapiro L,, Nabel GJ,, Mascola JR,, Kwong PD . 2010. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329 : 811 817.[PubMed] [CrossRef]
33. Bonsignori M,, Hwang KK,, Chen X,, Tsao CY,, Morris L,, Gray E,, Marshall DJ,, Crump JA,, Kapiga SH,, Sam NE,, Sinangil F,, Pancera M,, Yongping Y,, Zhang B,, Zhu J,, Kwong PD,, O’Dell S,, Mascola JR,, Wu L,, Nabel GJ,, Phogat S,, Seaman MS,, Whitesides JF,, Moody MA,, Kelsoe G,, Yang X,, Sodroski J,, Shaw GM,, Montefiori DC,, Kepler TB,, Tomaras GD,, Alam SM,, Liao HX,, Haynes BF . 2011. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol 85 : 9998 10009.[PubMed] [CrossRef]
34. Falkowska E,, Ramos A,, Feng Y,, Zhou T,, Moquin S,, Walker LM,, Wu X,, Seaman MS,, Wrin T,, Kwong PD,, Wyatt RT,, Mascola JR,, Poignard P,, Burton DR . 2012. PGV04, an HIV-1 gp120 CD4 binding site antibody, is broad and potent in neutralization but does not induce conformational changes characteristic of CD4. J Virol 86 : 4394 4403.[PubMed] [CrossRef]
35. Kwong PD,, Mascola JR,, Nabel GJ . 2013. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol 13 : 693 701.[PubMed] [CrossRef]
36. Zhou T,, Zhu J,, Wu X,, Moquin S,, Zhang B,, Acharya P,, Georgiev IS,, Altae-Tran HR,, Chuang GY,, Joyce MG,, Do Kwon Y,, Longo NS,, Louder MK,, Luongo T,, McKee K,, Schramm CA,, Skinner J,, Yang Y,, Yang Z,, Zhang Z,, Zheng A,, Bonsignori M,, Haynes BF,, Scheid JF,, Nussenzweig MC,, Simek M,, Burton DR,, Koff WC,, Mullikin JC,, Connors M,, Shapiro L,, Nabel GJ,, Mascola JR,, Kwong PD . 2013. Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity 39 : 245 258.[PubMed] [CrossRef]
37. Alam SM,, Dennison SM,, Aussedat B,, Vohra Y,, Park PK,, Fernandez-Tejada A,, Stewart S,, Jaeger FH,, Anasti K,, Blinn JH,, Kepler TB,, Bonsignori M,, Liao HX,, Sodroski JG,, Danishefsky SJ,, Haynes BF . 2013. Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors. Proc Natl Acad Sci USA 110 : 18214 18219.[PubMed] [CrossRef]
38. Jardine J,, Julien JP,, Menis S,, Ota T,, Kalyuzhniy O,, McGuire A,, Sok D,, Huang PS,, MacPherson S,, Jones M,, Nieusma T,, Mathison J,, Baker D,, Ward AB,, Burton DR,, Stamatatos L,, Nemazee D,, Wilson IA,, Schief WR . 2013. Rational HIV immunogen design to target specific germline B cell receptors. Science 340 : 711 716.[PubMed] [CrossRef]
39. Moldt B,, Rakasz EG,, Schultz N,, Chan-Hui PY,, Swiderek K,, Weisgrau KL,, Piaskowski SM,, Bergman Z,, Watkins DI,, Poignard P,, Burton DR . 2012. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci USA 109 : 18921 18925.[PubMed] [CrossRef]
40. Asokan A . 2010. Reengineered AAV vectors: old dog, new tricks. Discov Med 9 : 399 403.[PubMed]
41. Coura Rdos S,, Nardi NB . 2007. The state of the art of adeno-associated virus-based vectors in gene therapy. Virol J 4 : 99. doi:10.1186/1743-422X-4-99 [PubMed] [CrossRef]
42. Daya S,, Berns KI . 2008. Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev 21 : 583 593.[PubMed] [CrossRef]
43. Nowrouzi A,, Penaud-Budloo M,, Kaeppel C,, Appelt U,, Le Guiner C,, Moullier P,, von Kalle C,, Snyder RO,, Schmidt M . 2012. Integration frequency and intermolecular recombination of rAAV vectors in non-human primate skeletal muscle and liver. Mol Ther 20 : 1177 1186.[PubMed] [CrossRef]
44. Penaud-Budloo M,, Le Guiner C,, Nowrouzi A,, Toromanoff A,, Cherel Y,, Chenuaud P,, Schmidt M,, von Kalle C,, Rolling F,, Moullier P,, Snyder RO . 2008. Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle. J Virol 82 : 7875 7885.[PubMed] [CrossRef]
45. Schnepp BC,, Clark KR,, Klemanski DL,, Pacak CA,, Johnson PR . 2003. Genetic fate of recombinant adeno-associated virus vector genomes in muscle. J Virol 77 : 3495 3504.[PubMed] [CrossRef]
46. Aalbers CJ,, Tak PP,, Vervoordeldonk MJ . 2011. Advancements in adeno-associated viral gene therapy approaches: exploring a new horizon. F1000 Med Rep 3 : 17. doi:10.3410/M3-17. [PubMed] [CrossRef]
47. Lewis AD,, Chen R,, Montefiori DC,, Johnson PR,, Clark KR . 2002. Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer. J Virol 76 : 8769 8775.[PubMed] [CrossRef]
48. Fang JM,, Qian JJ,, Yi SY,, Harding TC,, Tu GH,, VanRoey M,, Jooss K . 2005. Stable antibody expression at therapeutic levels using the 2A peptide. Nat Biotechnol 23 : 584 590.[PubMed] [CrossRef]
49. Ashkenazi A,, Chamow SM . 1997. Immunoadhesins as research tools and therapeutic agents. Curr Opin Immunol 9 : 195 200.[PubMed] [CrossRef]
50. Capon DJ,, Chamow SM,, Mordenti J,, Marsters SA,, Gregory T,, Mitsuya H,, Byrn RA,, Lucas C,, Wurm FM,, Groopman JE,, Broder S,, Smith DH . 1989. Designing CD4 immunoadhesins for AIDS therapy. Nature 337 : 525 531.[PubMed] [CrossRef]
51. Limberis MP,, Adam VS,, Wong G,, Gren J,, Kobasa D,, Ross TM,, Kobinger GP,, Tretiakova A,, Wilson JM . 2013. Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza. Sci Transl Med 5 : 187ra172. doi:10.1126/scitranslmed.3006299 [PubMed] [CrossRef]
52. Weinblatt ME,, Bathon JM,, Kremer JM,, Fleischmann RM,, Schiff MH,, Martin RW,, Baumgartner SW,, Park GS,, Mancini EL,, Genovese MC . 2011. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res (Hoboken) 63 : 373 382.[PubMed]
53. Johnson WE,, Sanford H,, Schwall L,, Burton DR,, Parren PW,, Robinson JE,, Desrosiers RC . 2003. Assorted mutations in the envelope gene of simian immunodeficiency virus lead to loss of neutralization resistance against antibodies representing a broad spectrum of specificities. J Virol 77 : 9993 10003.[PubMed] [CrossRef]
54. Allaway GP,, Ryder AM,, Beaudry GA,, Maddon PJ . 1993. Synergistic inhibition of HIV-1 envelope-mediated cell fusion by CD4-based molecules in combination with antibodies to gp120 or gp41. AIDS Res Hum Retroviruses 9 : 581 587.[PubMed] [CrossRef]
55. Balazs AB,, Chen J,, Hong CM,, Rao DS,, Yang L,, Baltimore D . 2012. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481 : 81 84.[PubMed] [CrossRef]
56. Horwitz JA,, Halper-Stromberg A,, Mouquet H,, Gitlin AD,, Tretiakova A,, Eisenreich TR,, Malbec M,, Gravemann S,, Billerbeck E,, Dorner M,, Buning H,, Schwartz O,, Knops E,, Kaiser R,, Seaman MS,, Wilson JM,, Rice CM,, Ploss A,, Bjorkman PJ,, Klein F,, Nussenzweig MC . 2013. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc Natl Acad Sci USA 110 : 16538 16543.[PubMed] [CrossRef]
57. Mouquet H,, Scharf L,, Euler Z,, Liu Y,, Eden C,, Scheid JF,, Halper-Stromberg A,, Gnanapragasam PN,, Spencer DI,, Seaman MS,, Schuitemaker H,, Feizi T,, Nussenzweig MC,, Bjorkman PJ . 2012. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci USA 109 : E3268 E3277.[PubMed] [CrossRef]
58. Klein F,, Halper-Stromberg A,, Horwitz JA,, Gruell H,, Scheid JF,, Bournazos S,, Mouquet H,, Spatz LA,, Diskin R,, Abadir A,, Zang T,, Dorner M,, Billerbeck E,, Labitt RN,, Gaebler C,, Marcovecchio PM,, Incesu RB,, Eisenreich TR,, Bieniasz PD,, Seaman MS,, Bjorkman PJ,, Ravetch JV,, Ploss A,, Nussenzweig MC . 2012. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492 : 118 122.[PubMed] [CrossRef]
59. Skaricic D,, Traube C,, De B,, Joh J,, Boyer J,, Crystal RG,, Worgall S . 2008. Genetic delivery of an anti-RSV antibody to protect against pulmonary infection with RSV. Virology 378 : 79 85.[PubMed] [CrossRef]
60. Corti D,, Voss J,, Gamblin SJ,, Codoni G,, Macagno A,, Jarrossay D,, Vachieri SG,, Pinna D,, Minola A,, Vanzetta F,, Silacci C,, Fernandez-Rodriguez BM,, Agatic G,, Bianchi S,, Giacchetto-Sasselli I,, Calder L,, Sallusto F,, Collins P,, Haire LF,, Temperton N,, Langedijk JP,, Skehel JJ,, Lanzavecchia A . 2011. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333 : 850 856.[PubMed] [CrossRef]
61. Limberis MP,, Racine T,, Kobasa D,, Li Y,, Gao GF,, Kobinger G,, Wilson JM . 2013. Vectored expression of a broadly neutralizing antibody (FI6) in mouse airway provides partial protection against a new avian influenza A (H7N9) virus. Clin Vaccine Immunol 20 : 1836 1837.[PubMed] [CrossRef]
62. Balazs AB,, Bloom JD,, Hong CM,, Rao DS,, Baltimore D . 2013. Broad protection against influenza infection by vectored immunoprophylaxis in mice. Nat Biotechnol 31 : 647 652.[PubMed] [CrossRef]
63. Sui J,, Hwang WC,, Perez S,, Wei G,, Aird D,, Chen LM,, Santelli E,, Stec B,, Cadwell G,, Ali M,, Wan H,, Murakami A,, Yammanuru A,, Han T,, Cox NJ,, Bankston LA,, Donis RO,, Liddington RC,, Marasco WA . 2009. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16 : 265 273.[PubMed] [CrossRef]
64. Throsby M,, van den Brink E,, Jongeneelen M,, Poon LL,, Alard P,, Cornelissen L,, Bakker A,, Cox F,, van Deventer E,, Guan Y,, Cinatl J,, ter Meulen J,, Lasters I,, Carsetti R,, Peiris M,, de Kruif J,, Goudsmit J . 2008. Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS One 3 : e3942. doi:10.1371/journal.pone.0003942 [CrossRef]
65. Hicks MJ,, Rosenberg JB,, De BP,, Pagovich OE,, Young CN,, Qiu JP,, Kaminsky SM,, Hackett NR,, Worgall S,, Janda KD,, Davisson RL,, Crystal RG . 2012. AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation. Sci Transl Med 4 : 140ra187. doi:10.1126/scitranslmed.3003611 [PubMed] [CrossRef]
66. Rosenberg JB,, Hicks MJ,, De BP,, Pagovich O,, Frenk E,, Janda KD,, Wee S,, Koob GF,, Hackett NR,, Kaminsky SM,, Worgall S,, Tignor N,, Mezey JG,, Crystal RG . 2012. AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior. Hum Gene Ther 23 : 451 459.[PubMed] [CrossRef]
67. Keizer RJ,, Huitema AD,, Schellens JH,, Beijnen JH . 2010. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49 : 493 507.[PubMed] [CrossRef]
68. Kessler M,, Goldsmith D,, Schellekens H . 2006. Immunogenicity of biopharmaceuticals. Nephrol Dial Transplant 21( Suppl 5) : 9 12.[PubMed] [CrossRef]
69. Fang J,, Yi S,, Simmons A,, Tu GH,, Nguyen M,, Harding TC,, VanRoey M,, Jooss K . 2007. An antibody delivery system for regulated expression of therapeutic levels of monoclonal antibodies in vivo. Mol Ther 15 : 1153 1159.[PubMed]
70. Rivera VM,, Gao GP,, Grant RL,, Schnell MA,, Zoltick PW,, Rozamus LW,, Clackson T,, Wilson JM . 2005. Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood 105 : 1424 1430.[PubMed] [CrossRef]
71. Nguyen M,, Huan-Tu G,, Gonzalez-Edick M,, Rivera VM,, Clackson T,, Jooss KU,, Harding TC . 2007. Rapamycin-regulated control of antiangiogenic tumor therapy following rAAV-mediated gene transfer. Mol Ther 15 : 912 920.[PubMed] [CrossRef]
72. Schnepp BC,, Johnson PR . 2014. Adeno-associated virus delivery of broadly neutralizing antibodies. Curr Opin HIV AIDS 9 : 205 256.[PubMed] [CrossRef]


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Vector-mediated antibody gene transfer studies

Citation: Schnepp B, Johnson P. 2015. Vector-Mediated Antibody Expression, p 427-440. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0016-2014

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