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. 1996 Oct;70(10):6751–6758. doi: 10.1128/jvi.70.10.6751-6758.1996

The consequence of passive administration of an anti-human immunodeficiency virus type 1 neutralizing monoclonal antibody before challenge of chimpanzees with a primary virus isolate.

A J Conley 1, I I Kessler JA 1, L J Boots 1, P M McKenna 1, W A Schleif 1, E A Emini 1, G E Mark III 1, H Katinger 1, E K Cobb 1, S M Lunceford 1, S R Rouse 1, K K Murthy 1
PMCID: PMC190718  PMID: 8794312

Abstract

The anti-gp41 virus neutralizing monoclonal antibody 2F5 was infused into chimpanzees, which were then given an intravenous challenge with a primary human immunodeficiency virus type I (HIV-1) isolate. In two control animals, the infection was established immediately, as evidenced by positive cell-associated DNA PCR and serum RNA PCR tests within 1 week, seroconversion by 4 weeks, and development of lymphadenopathy in this acute phase. Serum RNA PCR tests were negative in one of the two antibody-infused animals until week 8 and in the other antibody-infused animal until week 12; both animals seroconverted at week 14. The peak of measurable virus-specific serum RNA was delayed until week 16 in one antibody-infused animal. Virus-specific RNA in the other animal did not reach levels comparable to those in the other animals through 1 year of follow-up studies. Virus was isolated from the week 16 blood sample from one infused animal. Virus was not isolated from peripheral blood of the second animal but was isolated from lymph node cells taken at week 36. The infection of untreated chimpanzees with this primary isolate appears robust. Use of this isolate should widen the scope of possible experiments in the chimpanzee model. This antibody infusion study indicates that neutralizing antibody, when present at the time of challenge, affects the timing and level of infection and remains influential after it can no longer be detected in the peripheral circulation. It is possible that preexisting, neutralizing antibodies (passively administered or actively elicited) affect the course of acute-phase virus replication in humans. It remains to be established whether these immunologically mediated early effects will influence the course of HIV-1 disease.

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Selected References

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  1. Arizono H., Ishii S., Nagao T., Kudo S., Sasaki S., Kondo S., Kiyoki M. Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. First communication: plasma concentration, distribution, metabolism and excretion of the new monoclonal antibody, regavirumab after intravenous administration in rats and rabbits. Arzneimittelforschung. 1994 Jul;44(7):890–898. [PubMed] [Google Scholar]
  2. Arthur L. O., Bess J. W., Jr, Waters D. J., Pyle S. W., Kelliher J. C., Nara P. L., Krohn K., Robey W. G., Langlois A. J., Gallo R. C. Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120. J Virol. 1989 Dec;63(12):5046–5053. doi: 10.1128/jvi.63.12.5046-5053.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  4. Berman P. W., Murthy K. K., Wrin T., Vennari J. C., Cobb E. K., Eastman D. J., Champe M., Nakamura G. R., Davison D., Powell M. F. Protection of MN-rgp120-immunized chimpanzees from heterologous infection with a primary isolate of human immunodeficiency virus type 1. J Infect Dis. 1996 Jan;173(1):52–59. doi: 10.1093/infdis/173.1.52. [DOI] [PubMed] [Google Scholar]
  5. Cao J., Bergeron L., Helseth E., Thali M., Repke H., Sodroski J. Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol. 1993 May;67(5):2747–2755. doi: 10.1128/jvi.67.5.2747-2755.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Conley A. J., Conard P., Bondy S., Dolan C. A., Hannah J., Leanza W. J., Marburg S., Rivetna M., Rusiecki V. K., Sugg E. E. Immunogenicity of synthetic HIV-1 gp120 V3-loop peptide-conjugate immunogens. Vaccine. 1994 Apr;12(5):445–451. doi: 10.1016/0264-410x(94)90123-6. [DOI] [PubMed] [Google Scholar]
  7. Conley A. J., Gorny M. K., Kessler J. A., 2nd, Boots L. J., Ossorio-Castro M., Koenig S., Lineberger D. W., Emini E. A., Williams C., Zolla-Pazner S. Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D. J Virol. 1994 Nov;68(11):6994–7000. doi: 10.1128/jvi.68.11.6994-7000.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Conley A. J., Kessler J. A., 2nd, Boots L. J., Tung J. S., Arnold B. A., Keller P. M., Shaw A. R., Emini E. A. Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3348–3352. doi: 10.1073/pnas.91.8.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ditzel H. J., Binley J. M., Moore J. P., Sodroski J., Sullivan N., Sawyer L. S., Hendry R. M., Yang W. P., Barbas C. F., 3rd, Burton D. R. Neutralizing recombinant human antibodies to a conformational V2- and CD4-binding site-sensitive epitope of HIV-1 gp120 isolated by using an epitope-masking procedure. J Immunol. 1995 Jan 15;154(2):893–906. [PubMed] [Google Scholar]
  10. Emini E. A., Schleif W. A., Nunberg J. H., Conley A. J., Eda Y., Tokiyoshi S., Putney S. D., Matsushita S., Cobb K. E., Jett C. M. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992 Feb 20;355(6362):728–730. doi: 10.1038/355728a0. [DOI] [PubMed] [Google Scholar]
  11. Fultz P. N., Nara P., Barre-Sinoussi F., Chaput A., Greenberg M. L., Muchmore E., Kieny M. P., Girard M. Vaccine protection of chimpanzees against challenge with HIV-1-infected peripheral blood mononuclear cells. Science. 1992 Jun 19;256(5064):1687–1690. doi: 10.1126/science.256.5064.1687. [DOI] [PubMed] [Google Scholar]
  12. Girard M., Kieny M. P., Pinter A., Barre-Sinoussi F., Nara P., Kolbe H., Kusumi K., Chaput A., Reinhart T., Muchmore E. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542–546. doi: 10.1073/pnas.88.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Girard M., Meignier B., Barré-Sinoussi F., Kieny M. P., Matthews T., Muchmore E., Nara P. L., Wei Q., Rimsky L., Weinhold K. Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1. J Virol. 1995 Oct;69(10):6239–6248. doi: 10.1128/jvi.69.10.6239-6248.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gorny M. K., Conley A. J., Karwowska S., Buchbinder A., Xu J. Y., Emini E. A., Koenig S., Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. J Virol. 1992 Dec;66(12):7538–7542. doi: 10.1128/jvi.66.12.7538-7542.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gorny M. K., Moore J. P., Conley A. J., Karwowska S., Sodroski J., Williams C., Burda S., Boots L. J., Zolla-Pazner S. Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1. J Virol. 1994 Dec;68(12):8312–8320. doi: 10.1128/jvi.68.12.8312-8320.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gorny M. K., Xu J. Y., Gianakakos V., Karwowska S., Williams C., Sheppard H. W., Hanson C. V., Zolla-Pazner S. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238–3242. doi: 10.1073/pnas.88.8.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Heath S. L., Tew J. G., Tew J. G., Szakal A. K., Burton G. F. Follicular dendritic cells and human immunodeficiency virus infectivity. Nature. 1995 Oct 26;377(6551):740–744. doi: 10.1038/377740a0. [DOI] [PubMed] [Google Scholar]
  18. Johnson B. K., Stone G. A., Godec M. S., Asher D. M., Gajdusek D. C., Gibbs C. J., Jr Long-term observations of human immunodeficiency virus-infected chimpanzees. AIDS Res Hum Retroviruses. 1993 Apr;9(4):375–378. doi: 10.1089/aid.1993.9.375. [DOI] [PubMed] [Google Scholar]
  19. Kahn J. O., Steimer K. S., Baenziger J., Duliege A. M., Feinberg M., Elbeik T., Chesney M., Murcar N., Chernoff D., Sinangil F. Clinical, immunologic, and virologic observations related to human immunodeficiency virus (HIV) type 1 infection in a volunteer in an HIV-1 vaccine clinical trial. J Infect Dis. 1995 May;171(5):1343–1347. doi: 10.1093/infdis/171.5.1343. [DOI] [PubMed] [Google Scholar]
  20. Moore J. P., Trkola A., Korber B., Boots L. J., Kessler J. A., 2nd, McCutchan F. E., Mascola J., Ho D. D., Robinson J., Conley A. J. A human monoclonal antibody to a complex epitope in the V3 region of gp120 of human immunodeficiency virus type 1 has broad reactivity within and outside clade B. J Virol. 1995 Jan;69(1):122–130. doi: 10.1128/jvi.69.1.122-130.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Muster T., Steindl F., Purtscher M., Trkola A., Klima A., Himmler G., Rüker F., Katinger H. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol. 1993 Nov;67(11):6642–6647. doi: 10.1128/jvi.67.11.6642-6647.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Neurath A. R., Strick N., Lin K., Jiang S. Multifaceted consequences of anti-gp41 monoclonal antibody 2F5 binding to HIV type 1 virions. AIDS Res Hum Retroviruses. 1995 Jun;11(6):687–696. doi: 10.1089/aid.1995.11.687. [DOI] [PubMed] [Google Scholar]
  23. Pardridge W. M., Buciak J., Yang J., Diagne A. Treatment of human immunodeficiency virus-infected lymphocytes with cationized human immunoglobulins. J Infect Dis. 1994 Sep;170(3):563–569. doi: 10.1093/infdis/170.3.563. [DOI] [PubMed] [Google Scholar]
  24. Phillips A. N. Reduction of HIV concentration during acute infection: independence from a specific immune response. Science. 1996 Jan 26;271(5248):497–499. doi: 10.1126/science.271.5248.497. [DOI] [PubMed] [Google Scholar]
  25. Purtscher M., Trkola A., Gruber G., Buchacher A., Predl R., Steindl F., Tauer C., Berger R., Barrett N., Jungbauer A. A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1994 Dec;10(12):1651–1658. doi: 10.1089/aid.1994.10.1651. [DOI] [PubMed] [Google Scholar]
  26. Safrit J. T., Koup R. A. The immunology of primary HIV infection: which immune responses control HIV replication? Curr Opin Immunol. 1995 Aug;7(4):456–461. doi: 10.1016/0952-7915(95)80088-3. [DOI] [PubMed] [Google Scholar]
  27. Sattentau Q. J., Zolla-Pazner S., Poignard P. Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. Virology. 1995 Jan 10;206(1):713–717. doi: 10.1016/s0042-6822(95)80094-8. [DOI] [PubMed] [Google Scholar]
  28. Schleif W. A., Murthy K. K., Sardana V. V., Schneider C. L., Byrnes V. W., Cobb K. E., Roth E., Wolfgang J. A., Hoffman J. M., Smith A. M. Attempted prophylaxis of human immunodeficiency virus type 1 infection in chimpanzees with a nonnucleoside reverse transcriptase inhibitor. AIDS Res Hum Retroviruses. 1994 Jan;10(1):107–110. doi: 10.1089/aid.1994.10.107. [DOI] [PubMed] [Google Scholar]
  29. Schuitemaker H., Meyaard L., Kootstra N. A., Dubbes R., Otto S. A., Tersmette M., Heeney J. L., Miedema F. Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. J Infect Dis. 1993 Nov;168(5):1140–1147. doi: 10.1093/infdis/168.5.1140. [DOI] [PubMed] [Google Scholar]
  30. Scott C. F., Jr, Silver S., Profy A. T., Putney S. D., Langlois A., Weinhold K., Robinson J. E. Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8597–8601. doi: 10.1073/pnas.87.21.8597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shibata R., Hoggan M. D., Broscius C., Englund G., Theodore T. S., Buckler-White A., Arthur L. O., Israel Z., Schultz A., Lane H. C. Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo. J Virol. 1995 Jul;69(7):4453–4462. doi: 10.1128/jvi.69.7.4453-4462.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stephens S., Emtage S., Vetterlein O., Chaplin L., Bebbington C., Nesbitt A., Sopwith M., Athwal D., Novak C., Bodmer M. Comprehensive pharmacokinetics of a humanized antibody and analysis of residual anti-idiotypic responses. Immunology. 1995 Aug;85(4):668–674. [PMC free article] [PubMed] [Google Scholar]
  33. Wang C. Y., Looney D. J., Li M. L., Walfield A. M., Ye J., Hosein B., Tam J. P., Wong-Staal F. Long-term high-titer neutralizing activity induced by octameric synthetic HIV-1 antigen. Science. 1991 Oct 11;254(5029):285–288. doi: 10.1126/science.254.5029.285. [DOI] [PubMed] [Google Scholar]
  34. Yasutomi Y., Koenig S., Woods R. M., Madsen J., Wassef N. M., Alving C. R., Klein H. J., Nolan T. E., Boots L. J., Kessler J. A. A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge. J Virol. 1995 Apr;69(4):2279–2284. doi: 10.1128/jvi.69.4.2279-2284.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. el-Amad Z., Murthy K. K., Higgins K., Cobb E. K., Haigwood N. L., Levy J. A., Steimer K. S. Resistance of chimpanzees immunized with recombinant gp120SF2 to challenge by HIV-1SF2. AIDS. 1995 Dec;9(12):1313–1322. doi: 10.1097/00002030-199512000-00003. [DOI] [PubMed] [Google Scholar]
  36. ten Haaft P., Cornelissen M., Goudsmit J., Koornstra W., Dubbes R., Niphuis H., Peeters M., Thiriart C., Bruck C., Heeney J. L. Virus load in chimpanzees infected with human immunodeficiency virus type 1: effect of pre-exposure vaccination. J Gen Virol. 1995 Apr;76(Pt 4):1015–1020. doi: 10.1099/0022-1317-76-4-1015. [DOI] [PubMed] [Google Scholar]

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