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Cited by 675

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge

Open access
Hansen, Scott G, Vieville, Cassandra, Whizin, Nathan, Coyne-Johnson, Lia, Siess, Don C, Drummond, Derek D, Legasse, Alfred W, Axthelm, Michael K, Oswald, Kelli, Trubey, Charles M, Piatak, Michael, Lifson, Jeffrey D, Nelson, Jay A, Jarvis, Michael A, Picker, Louis J·2009·Nature Medicine
DOI 10.1038/nm.1935
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Abstract

The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion and differentiation. We hypothesized that vaccines designed to maintain differentiated effector memory T cell (TEM cell) responses at viral entry sites might improve efficacy by impairing viral replication at its earliest stage, and we have therefore developed SIV protein-encoding vectors based on rhesus cytomegalovirus (RhCMV), the prototypical inducer of life-long TEM cell responses. RhCMV vectors expressing SIV Gag, Rev-Tat-Nef and Env persistently infected rhesus macaques, regardless of preexisting RhCMV immunity, and primed and maintained robust, SIV-specific CD4+ and CD8+ TEM cell responses (characterized by coordinate tumor necrosis factor, interferon-γ and macrophage inflammatory protein-1β expression, cytotoxic degranulation and accumulation at extralymphoid sites) in the absence of neutralizing antibodies. Compared to control rhesus macaques, these vaccinated rhesus macaques showed increased resistance to acquisition of progressive SIVmac239 infection upon repeated limiting-dose intrarectal challenge, including four macaques who controlled rectal mucosal infection without progressive systemic dissemination. These data suggest a new paradigm for AIDS vaccine development—vaccines capable of generating and maintaining HIV-specific TEM cells might decrease the incidence of HIV acquisition after sexual exposure.

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Metadata

Authors
Hansen, S. G., Vieville, C., Whizin, N., Coyne-Johnson, L., Siess, D. C., Drummond, D. D., Legasse, A. W., Axthelm, M. K., Oswald, K., Trubey, C. M., Piatak, M., Lifson, J. D., Nelson, J. A., Jarvis, M. A., & Picker, L. J.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2009-02-15
Volume
15
Issue
3
Pages
293-299
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.1935
OpenAlex
W2131674674
Cited by
675
References
41
FWCI
33.12
Type
journal article
Language
en
Open access
bronze

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