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Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Fuller, Deborah Heydenburg and Rajakumar, Premeela and Che, Jenny W and Narendran, Amithi and Nyaundi, Julia and Michael, Heather and Yager, Eric J and Stagnar, Cristy and Wahlberg, Brendon and Taber, Rachel and Haynes, Joel R and Cook, Fiona C and Ertl, Peter and Tite, John and Amedee, Angela M and Murphey-Corb, Michael (2012) Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques. PLoS One, 7 (3). e33715 - ?.

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Abstract

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Fuller, Deborah Heydenburg
Rajakumar, Premeela
Che, Jenny W
Narendran, Amithi
Nyaundi, Julia
Michael, Heather
Yager, Eric J
Stagnar, Cristy
Wahlberg, Brendonbwahlbrg@pitt.eduBWAHLBRG
Taber, Rachel
Haynes, Joel R
Cook, Fiona C
Ertl, Peter
Tite, John
Amedee, Angela M
Murphey-Corb, Michael
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLiang, ChenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 15 February 2012
Date Type: Acceptance
Journal or Publication Title: PLoS One
Volume: 7
Number: 3
Page Range: e33715 - ?
DOI or Unique Handle: 10.1371/journal.pone.0033715
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
Uncontrolled Keywords: AIDS Vaccines, Acquired Immunodeficiency Syndrome, Animals, Immunization, Interferon-gamma, Macaca mulatta, SAIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, Vaccines, DNA
Funders: NIAID NIH HHS (P01 AI055944), NIAID NIH HHS (R01 AI058801), PHS HHS (P01 A155844-01)
MeSH Headings: AIDS Vaccines--pharmacology; Acquired Immunodeficiency Syndrome--immunology; Acquired Immunodeficiency Syndrome--prevention & control; Animals; Immunization--methods; Interferon-gamma--immunology; Macaca mulatta; SAIDS Vaccines--pharmacology; Simian Acquired Immunodeficiency Syndrome--immunology; Simian Acquired Immunodeficiency Syndrome--prevention & control; Vaccines, DNA--microbiology
Other ID: NLM PMC3307760
PubMed Central ID: PMC3307760
PubMed ID: 22442716
Date Deposited: 13 Sep 2012 20:18
Last Modified: 24 Dec 2018 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/14158

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