Engagement of monocytes, NK cells, and CD4(+) Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition

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Engagement of monocytes, NK cells, and CD4(+) Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition

Gorini, Giacomo (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Fourati, Slim (författare): Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.

Vaccari, Monica (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

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Rahman, Mohammad Arif (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Gordon, Shari N. (författare): GlaxoSmithKline R&D, Dept Infect Dis, Res Triangle Pk, NC USA.

Brown, Dallas R. (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Law, Lynn (författare): Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.

Chang, Jean (författare): Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.

Green, Richard (författare): Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.

Barrenäs, Fredrik (författare): Uppsala universitet,Beräkningsbiologi och bioinformatik,Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA

Liyanage, Namal P. M. (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.;Ohio State Univ, Coll Med, Dept Microbial Infect & Immun, Columbus, OH 43210 USA.

Doster, Melvin N. (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Schifanella, Luca (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Bissa, Massimiliano (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

de Castro, Isabela Silva (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Washington-Parks, Robyn (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Galli, Veronica (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

Fuller, Deborah H. (författare): Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.

Santra, Sampa (författare): Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.

Agy, Michael (författare): Duke Univ, Sch Med, Div Surg Sci, Durham, NC USA.

Pal, Ranajit (författare): Adv Biosci Labs, Rockville, MD USA.

Palermo, Robert E. (författare): Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.

Tomaras, Georgia D. (författare): Duke Univ, Sch Med, Div Surg Sci, Durham, NC USA.

Shen, Xiaoying (författare): Duke Univ, Sch Med, Div Surg Sci, Durham, NC USA.

LaBranche, Celia C. (författare): Duke Univ, Sch Med, Div Surg Sci, Durham, NC USA.

Montefiori, David C. (författare): Duke Univ, Sch Med, Div Surg Sci, Durham, NC USA.

Venzon, David J. (författare): NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.

Trinh, Hung, V (författare): US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD USA.

Rao, Mangala (författare): US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD USA.

Gale, Michael, Jr. (författare): Univ Washington, Ctr Innate Immun & Immune Dis, Dept Immunol, Seattle, WA 98195 USA.;Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.

Sekaly, Rafick P. (författare): Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.

Franchini, Genoveffa (författare): NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.

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NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. (creator_code:org_t)

2020-03-12
2020
Engelska.
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 16:3

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://uu.diva-port... (primary) (Raw object); https://journals.plo...; https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

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The ALVAC-HIV/gp120/alum regimen tested in 8,197 human volunteers (61.4% males, 38.6% females) in the RV144 trial decreased the risk of HIV infection similarly in both sexes. The ALVAC-SIV/gp120/alum vaccine also reduced the risk of intrarectal SIVmac251 acquisition in both female and male vaccinated macaques at an average of 44% per exposure. In the current work, we tested whether this vaccine modality could also reduce the risk of intravaginal SIVmac251 exposure. In order to detect correlates of risk, we administered the virus by the intravaginal route and tested another vaccine regimen based on the vaccinia derivative poxvirus NYVAC in parallel. We demonstrate here that the ALVAC-SIV/gp120/alum regimen decreases the risk of vaginal SIVmac251 acquisition (50% vaccine efficacy) and, importantly, we confirmed that subsets of monocytes and CD4(+) T cells are correlates of risk of acquisition. In addition, we uncovered cytotoxic vaginal NKG2A(+) cells and gut-homing alpha(4)beta(7) positive plasmablasts as novel correlates of risk of intravaginal virus acquisition. In contrast, NYVAC-SIV vaccination induced high levels of activated T cells and did not protect against SIVmac251 acquisition. We examined the contrasting immune responses to better understand the correlate of protection and found that the unique ability of ALVAC-SIV to activate early interferon responses and the inflammasome during priming differentiates the two poxvirus vectors. This work demonstrates the reproducibility of the efficacy observed in the ALVAC-based regimen and defines novel correlates of risk in the rigorous SIVmac251 macaque model, establishing a benchmark for future improvement of this vaccine approach. The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIVmac251. Here, we demonstrate that the ALVAC-SIV/gp120/alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIVmac251 and we confirm that CD14(+) classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14(+) cells and/or their gene expression correlates with blood Type 1 CD4(+) T helper cells, alpha(4)beta(+)(7) plasmablasts, and vaginal cytocidal NKG2A(+) cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4(+)Ki67(+)CD38(+) and CD4(+)Ki67(+)alpha(4)beta(+)(7) T cells, higher SIV envelope-specific IFN-gamma producing cells, equivalent ADCC, and did not decrease the risk of SIVmac251 acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A(+) cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.

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NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Immunologi

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Engagement of monocytes, NK cells, and CD4(+) Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition

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