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* Vaccine Branch and
Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892;
California National Primate Research Center, University of California, Davis, CA 95616;
University of California, Irvine School of Medicine, Orange, CA 92868;
¶ Department of Microbiology, University of Washington, Seattle, WA 98195;
|| Seattle Biomedical Research Institute, Seattle, WA 98109; and
# Advanced Bioscience Laboratories, Kensington, MD 20895
Previously, Ab-dependent cellular cytotoxicity (ADCC) was significantly correlated with reduced acute viremia upon intrarectal SIVmac251 challenge of immunized rhesus macaques. To directly assess ADCC protective efficacy, six neonatal macaques were infused s.c. with immune IgG (220 mg/kg) purified from the immunized animals and positive for ADCC and Ab-dependent cell-mediated viral inhibition (ADCVI) activities. Six neonates received control IgG. The neonates were challenged twice orally with 105 50% inhibiting tissue culture-infective dose of SIVmac251 2 days post-IgG infusion. At challenge, plasma of neonates that received immune IgG did not neutralize SIVmac251 but had geometric mean ADCC titers of 48,130 and 232,850 against SIVmac251-infected and gp120-coated targets, respectively. Peak ADCVI activity varied from 62 to 81%. ADCC activity declined with the 2-wk IgG half-life but was boosted at wk 4, together with de novo ADCC-mediating Abs in controls, by postchallenge viremia. ADCVI activity was similarly induced. No protection, assessed by viral burdens, CD4 counts, and time to euthanasia was observed. Possible factors contributing to the discrepancy between the previous correlation and lack of protection here include: the high oral challenge dose compared with the 400-fold lower intrarectal dose; the challenge route with regard to viral dissemination and distribution of infused IgG; insufficient NK effector activity and/or poor functionality in newborns; insufficient immune IgG; and the possibility that the previous correlation of ADCC with protection was augmented by cellular immune responses also present at challenge. Future studies should explore additional challenge routes in juvenile macaques using higher amounts of potent IgG preparations.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, by National Institutes of Health Grant R01 AI52039 (to D.N.F.), and by a National Center for Research Resources supplement to the California National Primate Research Center Base Operating Grant (RR00169).
2 Address correspondence and reprint requests to Dr. Marjorie Robert-Guroff, National Institutes of Health, National Cancer Institute, 41 Medlars Drive, Building 41, Room D804, Bethesda, MD 20892-5065. E-mail address: guroffm{at}mail.nih.gov
3 Abbreviations used in this paper: ADCC, Ab-dependent cellular cytotoxicity; ADCVI, Ab-dependent cell-mediated virus inhibition; Ad, adenovirus; Ad5hr, Ad type 5 host range mutant; TCID50, 50% inhibiting tissue culture-infective dose; RFADCC, rapid fluorometric ADCC.
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  M. Huber, V. von Wyl, C. G. Ammann, H. Kuster, G. Stiegler, H. Katinger, R. Weber, M. Fischer, H. Stoiber, H. F. Gunthard, et al. Potent Human Immunodeficiency Virus-Neutralizing and Complement Lysis Activities of Antibodies Are Not Obligatorily Linked J. Virol., April 15, 2008; 82(8): 3834 - 3842. [Abstract] [Full Text] [PDF]
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