TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs

The Journal of Clinical Investigation
Liang ChengLishan Su

Abstract

Activation of HIV-1 reservoirs and induction of anti-HIV-1 T cells are critical to control HIV-1 rebound after combined antiretroviral therapy (cART). Here we evaluated in humanized mice (hu-mice) with persistent HIV-1 infection the therapeutic effect of TLR3 agonist and a CD40-targeting HIV-1 vaccine, which consists of a string of 5 highly conserved CD4+ and CD8+ T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol fused to the C-terminus of a recombinant anti-human CD40 antibody (αCD40.HIV5pep). We show that αCD40.HIV5pep vaccination coadministered with poly(I:C) adjuvant induced HIV-1-specific human CD8+ and CD4+ T cell responses in hu-mice. Interestingly, poly(I:C) treatment also reactivated HIV-1 reservoirs. When administrated in therapeutic settings in HIV-1-infected hu-mice under effective cART, αCD40.HIV5pep with poly(I:C) vaccination induced HIV-1-specific CD8+ T cells and reduced the level of cell-associated HIV-1 DNA (or HIV-1 reservoirs) in lymphoid tissues. Most strikingly, the vaccination significantly delayed HIV-1 rebound after cART cessation. In summary, the αCD40.HIV5pep with poly(I:C) vaccination approach both activates replication of HIV-1 reservoirs and enhances the anti-HIV-1 T cell response, leading to ...Continue Reading

References

Dec 23, 1988·Science·R NamikawaJ M McCune
Jan 26, 1995·The New England Journal of Medicine·G PantaleoL K Schrager
May 23, 1998·Annual Review of Immunology·I S Grewal, R A Flavell
Jun 27, 2001·AIDS·G PialouxUNKNOWN ANRS VAC 04 Study Team
Apr 24, 2003·Immunology·Tom A BarrAndrew W Heath
Jul 2, 2003·Nature Medicine·Norman L Letvin, Bruce D Walker
Sep 6, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Olivier LambotteUNKNOWN SEROCO-HEMOCO Study Group
Oct 24, 2006·Nature Medicine·Michael W MelkusJ Victor Garcia
Jan 30, 2007·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karoline W SchjetneBjarne Bogen
Sep 28, 2007·Nature·Ralph M Steinman, Jacques Banchereau
May 19, 2010·The Journal of Experimental Medicine·Sarah L JongbloedKristen J Radford
May 19, 2010·The Journal of Experimental Medicine·Lionel Franz PoulinCaetano Reis e Sousa
Oct 30, 2010·Immunity·Robert L CoffmanRobert A Seder
Nov 26, 2010·Annual Review of Medicine·Steven G Deeks
Apr 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Barbara J FlynnRobert Seder
Apr 17, 2012·Cellular & Molecular Immunology·Liguo Zhang, Lishan Su
Jul 28, 2012·Nature·Steven G Deeks
Oct 13, 2012·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Dec 21, 2012·The Journal of Experimental Medicine·Matthieu PerreauGiuseppe Pantaleo
Apr 2, 2013·Lancet·Christine KatlamaRafick P Sekaly
Jul 31, 2013·Immunity·Karolina Palucka, Jacques Banchereau
Jun 10, 2014·Frontiers in Immunology·Lillian Cohn, Lélia Delamarre
Jul 12, 2014·Science·Dan H Barouch, Steven G Deeks
Sep 6, 2014·Nature Reviews. Immunology·Wolfgang KastenmüllerRobert A Seder
Nov 18, 2014·Nature Reviews. Microbiology·Nancie M ArchinDavid M Margolis

❮ Previous
Next ❯

Citations

Apr 12, 2019·Current Opinion in HIV and AIDS·Mar Naranjo-Gomez, Mireia Pelegrin
Aug 20, 2019·The Journal of Experimental Medicine·Franck J Barrat, Lishan Su
Jan 19, 2019·PeerJ·Yao LeiYongguang Zhang
Nov 5, 2019·Frontiers in Immunology·Amanda B MacedoAlberto Bosque
Aug 30, 2020·International Journal of Molecular Sciences·Huy NguyenVishwanath Venketaraman
Jul 1, 2020·Frontiers in Immunology·Janne Tegder MartinsenOle Schmeltz Søgaard
Jul 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga TarasovaVladimir Poroikov
Jan 24, 2019·Viruses·Jonathan Burnie, Christina Guzzo
Sep 29, 2020·Seminars in Immunology·Adam R WardR Brad Jones
Jul 30, 2021·PLoS Pathogens·Jérôme KervevanSylvain Cardinaud
Aug 21, 2021·Journal of Zhejiang University. Science. B·Yujuan ChenHuashan Yi
Aug 21, 2020·Current HIV Research·Edward K MainaRaphael M Lwembe
Sep 24, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Valentina CegliaGerard Zurawski
Dec 18, 2021·Frontiers in Immunology·Valentina CegliaJohn A Altin

❮ Previous
Next ❯

Datasets Mentioned

BETA
KM660791
KM660792

Methods Mentioned

BETA
flow cytometry
transfection
PCR
fluorescence-activated cell sorter

Software Mentioned

Extreme Limiting Dilution analysis
GraphPad
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.