title: Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.
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.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Borducchi
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Cabral
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Stephenson
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ng'ang'a
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Nkolola
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Brinkman
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Lee
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Jimenez
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jetton
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Jade
authors.initials: J
authors.lastname: Mondesir
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Shanell
authors.initials: S
authors.lastname: Mojta
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Abishek
authors.initials: A
authors.lastname: Chandrashekar
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Molloy
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138 USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gerold
authors.affiliation: Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138 USA.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Hill
authors.affiliation: Bioqual, Rockville, Maryland 20852, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.affiliation: Janssen Infectious Diseases and Vaccines, 2301 Leiden, The Netherlands.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pau
authors.affiliation: Janssen Infectious Diseases and Vaccines, 2301 Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Gilead Sciences, Foster City, California 94404, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hesselgesser
authors.affiliation: Gilead Sciences, Foster City, California 94404, USA.
authors.forename: Romas
authors.initials: R
authors.lastname: Geleziunas
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.|Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D013997:Time Factors; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*; D019562:Viral Load / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D051199:Toll-Like Receptor 7