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Volume 9 Supplement 2

AIDS Vaccine 2012

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Immune complexes can dampen inflammatory signaling at the mucosal surface during protective SIV vaccination


The long-term goal for an efficacious HIV vaccine is to provide sterilizing protection from HIV infection. Thus far, this scenario has only been achieved experimentally using live-attenuated SIV vaccines. As such, great interest lies in identifying correlates of protection from a successful host response to pathogenic SIV. To this end, we have used a global genomics approach, tissue analysis, and explant cultures to identify immune complex (IC) signaling as an important component of a protective host response in the female reproductive tract (FRT) of animals vaccinated with the live-attenuated virus known as SIV mac239 ΔNef.


RNA from cervical tissue was purified for microarray analysis. Significant genes were functionally classified and protein expression determined using single-cell analytical procedures for tissue sections. FRT tissue was removed from healthy, uninfected, adult Rhesus macaques and cervix isolated/dissected into small tissue pieces for ex vivo culturing. WT SIVmac251 32H alone or SIV-specific ICs were added drop-wise to mucosal surfaces of explants and incubated for 24 hr at 37oC / 5% CO2.


A genome-wide transcriptomics analysis revealed selective enrichment of an anti-inflammatory program upon virus exposure in SIVmac239-ΔNef-vaccinated animals, with localized expression of these anti-inflammatory mediators in the mucosal epithelium of the FRT, coinciding with dampened inflammation, limited CD4+ T cell infiltration, and stunted virus replication. Explant cultures derived from the FRT of Rhesus macaques were used as a physiological platform to identify the inhibitory Fc receptor for IgG, FcγRIIB, and carbohydrates in the Fc portion of SIV-specific ICs as centrally important in mediating this anti-inflammatory signaling program in mucosal epithelial cells.


These results highlight an unappreciated, non-neutralizing role for antiviral antibodies at mucosal surfaces and implicates the mucosal epithelial cell as an important host sensor that integrates external signals to elicit a host program that either promotes (inflammatory) or suppresses (anti-inflammatory) immunodeficiency virus infection.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Smith, A., Wietgrefe, S., Reilly, C. et al. Immune complexes can dampen inflammatory signaling at the mucosal surface during protective SIV vaccination. Retrovirology 9 (Suppl 2), O19 (2012).

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