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Nature. 2016 Dec 8;540(7632):284-287. doi: 10.1038/nature20583. Epub 2016 Nov 9.

Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
2
Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA.
3
Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138 USA.
4
Bioqual, Rockville, Maryland 20852, USA.
5
Janssen Infectious Diseases and Vaccines, 2301 Leiden, The Netherlands.
6
Gilead Sciences, Foster City, California 94404, USA.
7
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.

Abstract

The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost) and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.

PMID:
27841870
PMCID:
PMC5145754
DOI:
10.1038/nature20583
[Indexed for MEDLINE]
Free PMC Article

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