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* Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;
New England Primate Research Center, Southborough, MA 01772; and
Crucell Holland BV, Leiden, The Netherlands
A critical goal of vaccine development for a wide variety of pathogens is the induction of potent and durable mucosal immunity. However, it has been assumed that this goal would be difficult to achieve by systemic vaccination due to the anatomic and functional distinctness of the systemic and mucosal immune systems and the resultant compartmentalization of immune responses. In this study, we show that Ag-specific CD8+ T lymphocytes traffic efficiently to mucosal surfaces following systemic vaccination. Intramuscular immunization with recombinant adenovirus (rAd) vector-based vaccines expressing SIV Gag resulted in potent, durable, and functional CD8+ T lymphocyte responses at multiple mucosal effector sites in both mice and rhesus monkeys. In adoptive transfer studies in mice, vaccine-elicited systemic CD8+ T lymphocytes exhibited phenotypic plasticity, up-regulated mucosal homing integrins and chemokine receptors, and trafficked rapidly to mucosal surfaces. Moreover, the migration of systemic CD8+ T lymphocytes to mucosal compartments accounted for the vast majority of Ag-specific mucosal CD8+ T lymphocytes induced by systemic vaccination. Thus, i.m. vaccination can overcome immune compartmentalization and generate robust mucosal CD8+ T lymphocyte memory. These data demonstrate that the systemic and mucosal immune systems are highly coordinated following vaccination.
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 by National Institutes of Health Grants U19 AI066305, U19 AI078526, and R01 AI066924, Bill & Melinda Gates Foundation Grant 38614 (to D.H.B.), and National Institutes of Health Training Grant T32 AI07387 (to D.R.K.).
2 Address correspondence and reprint requests to Dr. Dan H. Barouch, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. E-mail address: dbarouch{at}bidmc.harvard.edu
3 Abbreviations used in this paper: rAd, recombinant adenovirus; VP, viral particle; IEL, intraepithelial lymphocyte; LPL, lamina propria lymphocyte.
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