@article{a80a0993008f4443a7ad5a03c3307e36,
title = "Comparison of systemic and mucosal vaccination: Impact on intravenous and rectal SIV challenge",
abstract = "Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus. We aimed to generate strong mucosal immune responses to simian immunodeficiency virus (SIV) in rhesus macaques by targeting recombinant adenovirus serotype 5 (rAd5) to the lung. The immunogenicity and efficacy of aerosol (AE) vaccination was compared with intramuscular (IM) delivery in either an intravenous (IV) or intrarectal (IR) SIV mac251 challenge model. Aerosolized rAd5 induced strong cellular responses in the lung and systemic humoral responses equivalent to IM. Strikingly, all immunization groups controlled acute viremia in the IV challenge model by 1-2 logs. By contrast, after IR challenge, only peak viremia was reduced by immunization, with no significant effect on SIV infection acquisition rate or mucosal CD4 T-cell preservation. Improved disease outcome was associated with pre-challenge cellular and humoral responses, while post-challenge T-cell responses were highly correlated with viremia control. The similar outcomes achieved by systemic and airway mucosal immunization support AE delivery as a safe, effective, and less invasive alternative to parenteral vaccination.",
author = "Bolton, {D. L.} and K. Song and Wilson, {R. L.} and Kozlowski, {P. A.} and Tomaras, {G. D.} and Keele, {B. F.} and Lovingood, {R. V.} and S. Rao and M. Roederer",
note = "Funding Information: We thank M. Louder and Dr J Mascola for performing SIV Env neutralization assays and Dr J Lifson of SAIC-Frederick and Dr T Denny of Duke University for plasma viral load measurements. We thank Dr B. Lafont of the Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, for major histocompatibility complex haplotype sequencing. We also thank JP Todd and A Ault for assisting with animal immunizations, challenges, and sampling scheduling, as well as T Jenkins and A Dodson of Bioqual for animal care and handling. Adenovirus viral stocks were kindly provided by J Gall of GenVec. We thank Vicki C Ashley and R Glenn Overman for technical assistance with the antibody measurements and all members of the ImmunoTechnology Section for insightful discussions. This work was supported in part by the National Institutes of Health grant AI058896 (to PAK) and the Louisiana Vaccine Center and the South Louisiana Institute for Infectious Disease Research sponsored by the Louisiana Board of Regents, by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by the National Cancer Institute, National Institutes of Health under contract HHSN266200400088C.",
year = "2012",
month = jan,
doi = "10.1038/mi.2011.45",
language = "English (US)",
volume = "5",
pages = "41--52",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "1",
}