title: Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239delta3 in adult and infant rhesus monkeys.
abstract: Variants of SIV containing a deletion in the nef gene are attenuated in adult macaques, where they provide protection from challenge with pathogenic SIV, but the mechanism of protection remains unknown. One of these attenuated variants carrying deletions in nef, vpr, and NRE (SIVmac239delta3) was recently found to be pathogenic in infant macaques exposed to the virus at birth. We investigated whether inadequate or inappropriate antiviral humoral immune responses could explain why this virus causes disease in infant macaques. Plasma samples from four infants infected with SIVmac251 and five infants and two adults infected with SIVmac239delta3 were evaluated for neutralizing Abs to a laboratory-passaged stock of SIVmac251, an animal challenge stock of SIVmac239/nef-open, and a stock of SIVmac239delta3 to which animals were exposed. Plasma samples were evaluated further for complement-mediated Ab-dependent enhancement (C'-ADE) of SIVmac239/nef-open in vitro. High-titer neutralizing Abs to SIVmac251 were detected in plasma samples from adults and most infants within 3 to 5 wk of infection with either virus. Neutralizing Abs to SIVmac239/nef-open and SIVmac239delta3 developed more slowly, being undetectable before 23 to 63 wk of infection. Timing, magnitude, and breadth of neutralizing Ab responses did not correlate with progression to disease or lack thereof and gave no indication of an impaired humoral immune response in infants. Furthermore, C'-ADE was detected equally in plasma samples from adults and infants. The results indicate that infection with SIVmac239delta3 causes disease in infant macaques despite their mounting of antiviral humoral immune responses comparable to those of adults.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: T W
authors.initials: TW
authors.lastname: Baba
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Bilska
authors.forename: R M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000367:Age Factors; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D003673:Defective Viruses / Q000276:immunology; D017353:Gene Deletion; D015754:Genes, nef; D008253:Macaca mulatta; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines