Matches in SemOpenAlex for { <https://semopenalex.org/work/W3085667316> ?p ?o ?g. }
- W3085667316 abstract "Abstract A therapeutic vaccine that induces lasting control of HIV infection has the potential to eliminate the need for lifelong adherence to antiretroviral therapy (ART). This study investigated the efficacy of a therapeutic DNA vaccine delivered with a novel combination of adjuvants and immunomodulators to augment T cell immunity in the blood and gut-associated lymphoid tissue. In SIV-infected rhesus macaques, a DNA vaccine delivered by intradermal electroporation and expressing SIV Env, Gag, and Pol, and a combination of adjuvant plasmids expressing the catalytic A1 subunit of E. coli heat labile enterotoxin (LTA1), IL-12, IL-33, retinaldehyde dehydrogenase 2 and the immunomodulators soluble PD-1 and soluble CD80, significantly enhanced the breadth and magnitude of Gag-specific IFN- γ T cell responses when compared to controls that were mock vaccinated or received the same DNA vaccine delivered by Gene Gun with a single adjuvant, the E. coli heat labile enterotoxin, LT. Notably, the DNA vaccine and adjuvant combination protected 3/5 animals from viral rebound, compared to only 1/4 mock vaccinated animals and 1/5 animals that received the DNA vaccine and LT. The lower viral burden among controllers during analytical treatment interruption significantly correlated with higher polyfunctional CD8 + T-cells (CD8 + T cells expressing 3 or more effector functions) in both mesenteric lymph nodes and blood measured during ART and analytical treatment interruption. Interestingly, controllers also had lower viral loads during acute infection and ART suggesting that inherent host-viral interactions induced prior to ART initiation likely influenced the response to therapeutic vaccination. These data indicate that gut mucosal immune responses combined with effective ART may play a key role in containing residual virus post-ART and highlight the need for therapeutic vaccines and adjuvants that can restore functional quality of peripheral and mucosal T cell responses before and during ART. Author Summary HIV has caused significant human disease and mortality since its emergence in the 1980s. Furthermore, although antiretroviral therapy (ART) effectively reduces viral replication, stopping ART leads to increased viral loads and disease progression in most HIV-infected people. A therapeutic vaccine could enable HIV-infected people to control their infection without ART, but none of the vaccines that were tested in clinical trials so far have induced long-lasting control of virus replication. Here, we used the SIV rhesus macaque model to test a therapeutic vaccine consisting of DNA expressing SIV proteins and a novel combination of adjuvants to boost virus-specific immune responses. We found that our vaccine strategy significantly enhanced SIV-specific T cell responses when compared to controls and protected 3/5 animals from viral rebound. We determined that lower levels of virus replication post-ART were associated with enhanced T cell immunity in the gut-draining lymph nodes and blood. Our study highlights the critical role of T cell immunity for control of SIV and HIV replication and demonstrates that a successful therapeutic vaccine for HIV will need to elicit potent T cell responses in both the blood and gut-associated tissues." @default.
- W3085667316 created "2020-09-21" @default.
- W3085667316 creator A5001931542 @default.
- W3085667316 creator A5013081084 @default.
- W3085667316 creator A5028856410 @default.
- W3085667316 creator A5046576045 @default.
- W3085667316 creator A5048434720 @default.
- W3085667316 creator A5054896256 @default.
- W3085667316 creator A5071313563 @default.
- W3085667316 creator A5072931108 @default.
- W3085667316 creator A5074212929 @default.
- W3085667316 date "2020-09-16" @default.
- W3085667316 modified "2023-09-27" @default.
- W3085667316 title "Protection from viral rebound after therapeutic vaccination with an adjuvanted DNA vaccine is associated with SIV-specific polyfunctional CD8 T cells in the blood and mesenteric lymph nodes" @default.
- W3085667316 cites W162579416 @default.
- W3085667316 cites W1928648264 @default.
- W3085667316 cites W1977290996 @default.
- W3085667316 cites W1982320535 @default.
- W3085667316 cites W1987970975 @default.
- W3085667316 cites W1994047615 @default.
- W3085667316 cites W2008994596 @default.
- W3085667316 cites W2011811060 @default.
- W3085667316 cites W2014876227 @default.
- W3085667316 cites W2016488838 @default.
- W3085667316 cites W2026340875 @default.
- W3085667316 cites W2026814484 @default.
- W3085667316 cites W2030605921 @default.
- W3085667316 cites W2045178852 @default.
- W3085667316 cites W2046974680 @default.
- W3085667316 cites W2052149946 @default.
- W3085667316 cites W2056372405 @default.
- W3085667316 cites W2058798829 @default.
- W3085667316 cites W2061395308 @default.
- W3085667316 cites W2068414412 @default.
- W3085667316 cites W2075345074 @default.
- W3085667316 cites W2077914568 @default.
- W3085667316 cites W2079140075 @default.
- W3085667316 cites W2083616793 @default.
- W3085667316 cites W2089266967 @default.
- W3085667316 cites W2090669065 @default.
- W3085667316 cites W2090980433 @default.
- W3085667316 cites W2101533269 @default.
- W3085667316 cites W2115297961 @default.
- W3085667316 cites W2115580899 @default.
- W3085667316 cites W2121829018 @default.
- W3085667316 cites W2122389576 @default.
- W3085667316 cites W2122483069 @default.
- W3085667316 cites W2127517680 @default.
- W3085667316 cites W2132500169 @default.
- W3085667316 cites W2138165790 @default.
- W3085667316 cites W2145149316 @default.
- W3085667316 cites W2145266626 @default.
- W3085667316 cites W2149492547 @default.
- W3085667316 cites W2150484278 @default.
- W3085667316 cites W2159225279 @default.
- W3085667316 cites W2170704251 @default.
- W3085667316 cites W2309734431 @default.
- W3085667316 cites W2331534750 @default.
- W3085667316 cites W2523611151 @default.
- W3085667316 cites W2556485149 @default.
- W3085667316 cites W2573830854 @default.
- W3085667316 cites W2773291418 @default.
- W3085667316 cites W2797923168 @default.
- W3085667316 cites W2900099291 @default.
- W3085667316 cites W2910100593 @default.
- W3085667316 cites W2916773554 @default.
- W3085667316 cites W2952363783 @default.
- W3085667316 doi "https://doi.org/10.1101/2020.09.16.299511" @default.
- W3085667316 hasPublicationYear "2020" @default.
- W3085667316 type Work @default.
- W3085667316 sameAs 3085667316 @default.
- W3085667316 citedByCount "0" @default.
- W3085667316 crossrefType "posted-content" @default.
- W3085667316 hasAuthorship W3085667316A5001931542 @default.
- W3085667316 hasAuthorship W3085667316A5013081084 @default.
- W3085667316 hasAuthorship W3085667316A5028856410 @default.
- W3085667316 hasAuthorship W3085667316A5046576045 @default.
- W3085667316 hasAuthorship W3085667316A5048434720 @default.
- W3085667316 hasAuthorship W3085667316A5054896256 @default.
- W3085667316 hasAuthorship W3085667316A5071313563 @default.
- W3085667316 hasAuthorship W3085667316A5072931108 @default.
- W3085667316 hasAuthorship W3085667316A5074212929 @default.
- W3085667316 hasBestOaLocation W30856673161 @default.
- W3085667316 hasConcept C104317684 @default.
- W3085667316 hasConcept C154317977 @default.
- W3085667316 hasConcept C159047783 @default.
- W3085667316 hasConcept C167508917 @default.
- W3085667316 hasConcept C167672396 @default.
- W3085667316 hasConcept C202751555 @default.
- W3085667316 hasConcept C203014093 @default.
- W3085667316 hasConcept C22070199 @default.
- W3085667316 hasConcept C2777863537 @default.
- W3085667316 hasConcept C2778353597 @default.
- W3085667316 hasConcept C2779237934 @default.
- W3085667316 hasConcept C2780801004 @default.
- W3085667316 hasConcept C547475151 @default.
- W3085667316 hasConcept C55493867 @default.
- W3085667316 hasConcept C66999527 @default.
- W3085667316 hasConcept C71924100 @default.
- W3085667316 hasConcept C86803240 @default.