Using Computational Modeling to Optimize the Design of Antibodies That Trap Viruses in Mucus

ACS Infectious Diseases

Volumn 2, Issue 1, 2016, Pages 82-92

  Wessler, Timothy ^a   Chen, Alex ^a,g   McKinley, Scott A ^b   Cone, Richard ^c   Forest, M Gregory ^a,e   Lai, Samuel K ^d,e,f  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b Tulane University   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNC Hamner Institute for Drug Safety Sciences   (United States)

^e Biomedical Research Imaging Center   (United States)

^f UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^g GE GLOBAL RESEARCH   (United States)

Author keywords

cervicovaginal mucus; HIV; IgG; mucin; mucosal immunity; sexually transmitted infections

Indexed keywords

ANTIBODY; ANTIGEN; IMMUNOGLOBULIN G; MUCIN;

ANTIGEN BINDING; ARTICLE; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; MATHEMATICAL MODEL; MOLECULE; MUCUS; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; SEXUALLY TRANSMITTED DISEASE; SPERM; TIME; VAGINA EPITHELIUM; VIRION;

EID: 84964885473     PISSN: None     EISSN: 23738227     Source Type: Journal    
DOI: 10.1021/acsinfecdis.5b00108     Document Type: Article

References (49)

1. Casadevall, A. and Pirofski, L. A. (2012) A new synthesis for antibody-mediated immunity Nat. Immunol. 13 (1) 21-28 10.1038/ni.2184
2. Corthesy, B. (2010) Role of secretory immunoglobulin A and secretory component in the protection of mucosal surfaces Future Microbiol. 5 (5) 817-829 10.2217/fmb.10.39
3. Kozlowski, P. A. and Neutra, M. R. (2003) The role of mucosal immunity in prevention of HIV transmission Curr. Mol. Med. 3 (3) 217-228 10.2174/1566524033479852
4. Burton, D. R. and Mascola, J. R. (2015) Antibody responses to envelope glycoproteins in HIV-1 infection Nat. Immunol. 16 (6) 571-576 10.1038/ni.3158
5. van Gils, M. J. and Sanders, R. W. (2013) Broadly neutralizing antibodies against HIV-1: templates for a vaccine Virology 435 (1) 46-56 10.1016/j.virol.2012.10.004
6. Dunkelberger, J. R. and Song, W. C. (2010) Complement and its role in innate and adaptive immune responses Cell Res. 20 (1) 34-50 10.1038/cr.2009.139
7. Huber, M., Olson, W. C., and Trkola, A. (2008) Antibodies for HIV treatment and prevention: window of opportunity? Curr. Top. Microbiol. Immunol. 317, 39-66 10.1007/978-3-540-72146-8-2
8. Kilian, M. and Russell, M. W. (1994) Function of mucosal immunoglobulins. In Handbook of Mucosal Immunology (Ogra, P. L., Mestecky, J., Lamm, M. E., Strober, W., Bienenstock, J., and McGhee, J. R., Eds.) pp 127-137 Academic Press, San Diego, CA, USA.
9. Whaley, K. J., Zeitlin, L., Barratt, R. A., Hoen, T. E., and Cone, R. A. (1994) Passive immunization of the vagina protects mice against vaginal transmission of genital herpes infections J. Infect. Dis. 169 (3) 647-649 10.1093/infdis/169.3.647
10. Zeitlin, L., Whaley, K. J., Sanna, P. P., Moench, T. R., Bastidas, R., De Logu, A., Williamson, R. A., Burton, D. R., and Cone, R. A. (1996) Topically applied human recombinant monoclonal IgG1 antibody and its Fab and F(ab′)2 fragments protect mice from vaginal transmission of HSV-2 Virology 225 (1) 213-215 10.1006/viro.1996.0589
11. Veazey, R. S., Shattock, R. J., Pope, M., Kirijan, J. C., Jones, J., Hu, Q., Ketas, T., Marx, P. A., Klasse, P. J., Burton, D. R., and Moore, J. P. (2003) Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120 Nat. Med. 9 (3) 343-346 10.1038/nm833
12. Mascola, J. R., Stiegler, G., VanCott, T. C., Katinger, H., Carpenter, C. B., Hanson, C. E., Beary, H., Hayes, D., Frankel, S. S., Birx, D. L., and Lewis, M. G. (2000) Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies Nat. Med. 6 (2) 207-210 10.1038/72318
13. Chipperfield, E. J. and Evans, B. A. (1975) Effect of local infection and oral contraception on immunoglobulin levels in cervical mucus Infect. Immun. 11 (2) 215-221
14. Usala, S. J., Usala, F. O., Haciski, R., Holt, J. A., and Schumacher, G. F. (1989) IgG and IgA content of vaginal fluid during the menstrual cycle J. Reprod. Med. 34 (4) 292-294
15. Wang, Y. Y., Kannan, A., Nunn, K. L., Murphy, M. A., Subramani, D. B., Moench, T., Cone, R., and Lai, S. K. (2014) IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections Mucosal Immunol. 7 (5) 1036-1044 10.1038/mi.2013.120
16. Lai, S. K., Wang, Y. Y., Hida, K., Cone, R., and Hanes, J. (2010) Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses Proc. Natl. Acad. Sci. U. S. A. 107 (2) 598-603 10.1073/pnas.0911748107
17. Lai, S. K., Hida, K., Shukair, S., Wang, Y. Y., Figueiredo, A., Cone, R., Hope, T. J., and Hanes, J. (2009) Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus J. Virol. 83 (21) 11196-11200 10.1128/JVI.01899-08
18. Nunn, K. L., Wang, Y. Y., Harit, D., Humphrys, M. S., Ma, B., Cone, R., Ravel, J., and Lai, S. K. (2015) Enhanced trapping of HIV-1 by human cervicovaginal mucus is associated with Lactobacillus crispatus-dominant microbiota mBio 6 (5) e01084-15 10.1128/mBio.01084-15
19. Shukair, S. A., Allen, S. A., Cianci, G. C., Stieh, D. J., Anderson, M. R., Baig, S. M., Gioia, C. J., Spongberg, E. J., Kauffman, S. M., McRaven, M. D., Lakougna, H. Y., Hammond, C., Kiser, P. F., and Hope, T. J. (2013) Human cervicovaginal mucus contains an activity that hinders HIV-1 movement Mucosal Immunol. 6 (2) 427-434 10.1038/mi.2012.87
20. Saltzman, W. M., Radomsky, M. L., Whaley, K. J., and Cone, R. A. (1994) Antibody diffusion in human cervical mucus Biophys. J. 66 (2 Part 1) 508-515 10.1016/S0006-3495(94)80802-1
21. Olmsted, S. S., Padgett, J. L., Yudin, A. I., Whaley, K. J., Moench, T. R., and Cone, R. A. (2001) Diffusion of macromolecules and virus-like particles in human cervical mucus Biophys. J. 81 (4) 1930-1937 10.1016/S0006-3495(01)75844-4
22. McKinley, S. A., Chen, A., Shi, F., Wang, S., Mucha, P. J., Forest, M. G., and Lai, S. K. (2014) Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa PLoS One 9 (6) e100598 10.1371/journal.pone.0100598
23. Klein, F., Mouquet, H., Dosenovic, P., Scheid, J. F., Scharf, L., and Nussenzweig, M. C. (2013) Antibodies in HIV-1 vaccine development and therapy Science 341 (6151) 1199-204 10.1126/science.1241144
24. Whaley, K. J. and Mayer, K. H. (2014) Strategies for preventing mucosal cell-associated HIV transmission J. Infect. Dis. 210 (Suppl. 3) S674-S680 10.1093/infdis/jiu398
25. Chen, A., McKinley, S. A., Wang, S., Shi, F., Mucha, P. J., Forest, M. G., and Lai, S. K. (2014) Transient antibody-mucin interactions produce a dynamic molecular shield against viral invasion Biophys. J. 106 (9) 2028-2036 10.1016/j.bpj.2014.02.038
26. Smoluchowski, M. v. (1917) Versuch einer mathematischen Theorie der Koagulationskinetik kolloider Lösungen Z. Phys. Chem. 92, 129-168
27. Sherwood, J. K., Zeitlin, L., Whaley, K. J., Cone, R. A., and Saltzman, M. (1996) Controlled release of antibodies for long-term topical passive immunoprotection of female mice against genital herpes Nat. Biotechnol. 14 (4) 468-471 10.1038/nbt0496-468
28. Ramessar, K., Rademacher, T., Sack, M., Stadlmann, J., Platis, D., Stiegler, G., Labrou, N., Altmann, F., Ma, J., Stoger, E., Capell, T., and Christou, P. (2008) Cost-effective production of a vaginal protein microbicide to prevent HIV transmission Proc. Natl. Acad. Sci. U. S. A. 105 (10) 3727-3732 10.1073/pnas.0708841104
29. Whaley, K. J., Hiatt, A., and Zeitlin, L. (2011) Emerging antibody products and Nicotiana manufacturing Hum. Vaccines 7 (3) 349-356 10.4161/hv.7.3.14266
30. Liu, H. F., Ma, J., Winter, C., and Bayer, R. (2010) Recovery and purification process development for monoclonal antibody production mAbs 2 (5) 480-499 10.4161/mabs.2.5.12645
31. Zydney, A. L. (2015) Continuous downstream processing for high value biological products-a review Biotechnol. Bioeng. 25695 10.1002/bit.25695
32. Santra, S., Tomaras, G. D., Warrier, R., Nicely, N. I., Liao, H. X., Pollara, J., Liu, P., Alam, S. M., Zhang, R., Cocklin, S. L., Shen, X., Duffy, R., Xia, S. M., Schutte, R. J., Pemble Iv, C. W., Dennison, S. M., Li, H., Chao, A., Vidnovic, K., Evans, A., Klein, K., Kumar, A., Robinson, J., Landucci, G., Forthal, D. N., Montefiori, D. C., Kaewkungwal, J., Nitayaphan, S., Pitisuttithum, P., Rerks-Ngarm, S., Robb, M. L., Michael, N. L., Kim, J. H., Soderberg, K. A., Giorgi, E. E., Blair, L., Korber, B. T., Moog, C., Shattock, R. J., Letvin, N. L., Schmitz, J. E., Moody, M. A., Gao, F., Ferrari, G., Shaw, G. M., and Haynes, B. F. (2015) Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques PLoS Pathog. 11 (8) e1005042 10.1371/journal.ppat.1005042
33. 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, J. G., Francis, D. P., Stablein, D., Birx, D. L., Chunsuttiwat, S., Khamboonruang, C., Thongcharoen, P., Robb, M. L., Michael, N. L., Kunasol, P., and Kim, J. H. (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand N. Engl. J. Med. 361 (23) 2209-2220 10.1056/NEJMoa0908492
34. Jamison, P. L. and Gebhard, P. H. (1988) Penis size increase between flaccid and erect states: an analysis of the Kinsey data J. Sex Res. 24 (1) 177-183 10.1080/00224498809551408
35. Pendergrass, P. B., Belovicz, M. W., and Reeves, C. A. (2003) Surface area of the human vagina as measured from vinyl polysiloxane casts Gynecol. Obstet. Invest. 55 (2) 110-113 10.1159/000070184
36. Lai, S. K., O'Hanlon, D. E., Harrold, S., Man, S. T., Wang, Y. Y., Cone, R., and Hanes, J. (2007) Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus Proc. Natl. Acad. Sci. U. S. A. 104 (5) 1482-1487 10.1073/pnas.0608611104
37. Geonnotti, A. R. and Katz, D. F. (2006) Dynamics of HIV neutralization by a microbicide formulation layer: biophysical fundamentals and transport theory Biophys. J. 91 (6) 2121-2130 10.1529/biophysj.106.086322
38. Lai, B. E., Henderson, M. H., Peters, J. J., Walmer, D. K., and Katz, D. F. (2009) Transport theory for HIV diffusion through in vivo distributions of topical microbicide gels Biophys. J. 97 (9) 2379-2387 10.1016/j.bpj.2009.08.010
39. Gupta, P., Mellors, J., Kingsley, L., Riddler, S., Singh, M. K., Schreiber, S., Cronin, M., and Rinaldo, C. R. (1997) High viral load in semen of human immunodeficiency virus type 1-infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors J. Virol. 71 (8) 6271-6275
40. Rehan, N., Sobrero, A. J., and Fertig, J. W. (1975) The semen of fertile men: statistical analysis of 1300 men Fertil. Steril. 26 (6) 492-502
41. Scheid, J. F., Mouquet, H., Ueberheide, B., Diskin, R., Klein, F., Oliveira, T. Y., Pietzsch, J., Fenyo, D., Abadir, A., Velinzon, K., Hurley, A., Myung, S., Boulad, F., Poignard, P., Burton, D. R., Pereyra, F., Ho, D. D., Walker, B. D., Seaman, M. S., Bjorkman, P. J., Chait, B. T., and Nussenzweig, M. C. (2011) Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding Science 333 (6049) 1633-1637 10.1126/science.1207227
42. Zhu, P., Liu, J., Bess, J., Jr., Chertova, E., Lifson, J. D., Grise, H., Ofek, G. A., Taylor, K. A., and Roux, K. H. (2006) Distribution and three-dimensional structure of AIDS virus envelope spikes Nature 441 (7095) 847-852 10.1038/nature04817
43. Stone, A. and Gamble, C. J. (1959) The quantity of vaginal fluid Am. J. Obstet. Gynecol. 78 (2) 279-281
44. Owen, D. H. and Katz, D. F. (1999) A vaginal fluid simulant Contraception 59 (2) 91-95 10.1016/S0010-7824(99)00010-4
45. Chakraborty, H., Sen, P. K., Helms, R. W., Vernazza, P. L., Fiscus, S. A., Eron, J. J., Patterson, B. K., Coombs, R. W., Krieger, J. N., and Cohen, M. S. (2001) Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model AIDS 15 (5) 621-627 10.1097/00002030-200103300-00012
46. Magnus, C. and Regoes, R. R. (2010) Estimating the stoichiometry of HIV neutralization PLoS Comput. Biol. 6 (3) e1000713 10.1371/journal.pcbi.1000713
47. Yang, X., Kurteva, S., Lee, S., and Sodroski, J. (2005) Stoichiometry of antibody neutralization of human immunodeficiency virus type 1 J. Virol. 79 (6) 3500-3508 10.1128/JVI.79.6.3500-3508.2005
48. Schonning, K., Lund, O., Lund, O. S., and Hansen, J. E. (1999) Stoichiometry of monoclonal antibody neutralization of T-cell line-adapted human immunodeficiency virus type 1 J. Virol. 73 (10) 8364-8370
49. McLain, L. and Dimmock, N. J. (1994) Single- and multi-hit kinetics of immunoglobulin G neutralization of human immunodeficiency virus type 1 by monoclonal antibodies J. Gen. Virol. 75 (Part 6) 1457-1460 10.1099/0022-1317-75-6-1457