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Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian–human immunodeficiency virus infection

Nature Medicine volume 6, pages 200–206 (2000)Cite this article

Abstract

Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50–70% of all infected children seem to acquire HIV-1 shortly before or during delivery1. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission2,3. A simian immunodeficiency virus (SIV) macaque model has been developed4 that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV–vpu+ (refs. 5,6), a chimeric simian–human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV–vpu+ completely in vitro through synergistic interaction7. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV–vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV–vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.

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Figure 1: Neutralizing activity of plasma obtained from an uninfected mother–infant pair.
Figure 2: Monoclonal antibody pharmacokinetics and viral challenge.
Figure 3: Western blot analysis and ELISA of plasma samples.

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Acknowledgements

We thank C. Gallegos, B. Odlum and S. Sharp for the preparation of this manuscript. This work was supported in part by National Institutes of Health grants RO1 AI34266 and RO1 AI32330 to R.M.R. and RO1 AI26926 to L.A.C. and M.R.P. It was also supported by the Pediatric AIDS Foundation grant 50864PG23 to R.M.R. and by the Center for AIDS Research core grant IP30 28691 awarded to the Dana-Farber Cancer Institute as support for the Institute's AIDS research efforts. T.W.B. was a recipient of an NIH Clinical Investigator Development Award (KO8-AI01327). R.H-L. was supported by a grant from the Swiss National Science Foundation (fellowship number 823A-50315).

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  1. Seyoum Ayehunie

    Present address: MatTek Corporation, Ashland, Massachusetts, 01721, USA

Authors and Affiliations

  1. Department of Cancer Immonology and AIDS, Dana-Farber Cancer Institute, Boston, 02115 , Massachusetts, USA

    Timothy W. Baba, Vladimir Liska, Regina Hofmann-Lehmann, Josef Vlasak, Weidong Xu, Seyoum Ayehunie & Ruth M. Ruprecht

  2. Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USA

    Joel E. Wright

  3. Department of Medicine, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Timothy W. Baba, Vladimir Liska, Regina Hofmann-Lehmann, Josef Vlasak, Weidong Xu, Seyoum Ayehunie, Lisa A. Cavacini, Marshall R. Posner & Ruth M. Ruprecht

  4. Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, Boston, 02115, Massachusetts, USA

    Joel E. Wright

  5. Division of Newborn Medicine, Department of Pediatrics Tufts University School of Medicine, Boston, 02111, Massachusetts , USA

    Timothy W. Baba

  6. Beth Israel-Deaconess Medical Center, Boston , 02215, Massachusetts, USA

    Lisa A. Cavacini & Marshall R. Posner

  7. Institute of Applied Microbiology, Vienna, A-1190 , Austria

    Hermann Katinger & Gabriela Stiegler

  8. Department of Veterinary Sciences, University of Texas M.D. Anderson Cancer Center, Bastrop, 78602, Texas, USA

    Bruce J. Bernacky, Tahir A. Rizvi, Russell Schmidt, Lori R. Hill & Michale E. Keeling

  9. Harvard School of Public Health, Boston , 02115, Massachusetts, USA

    Yichen Lu

  10. Laboratory of Biochemical Pharmacology and Preclinical Pharmacology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Ting-Chao Chou

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  1. Timothy W. Baba
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Correspondence to Ruth M. Ruprecht.

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Baba, T., Liska, V., Hofmann-Lehmann, R. et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian–human immunodeficiency virus infection. Nat Med 6, 200–206 (2000). https://doi.org/10.1038/72309

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