Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

PLoS Pathogens
Sarah AuclairHaitao Hu

Abstract

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct pr...Continue Reading

References

Apr 15, 1999·Immunology Letters·E S RosenbergB D Walker
May 3, 2002·Nature·Daniel C DouekRichard A Koup
Apr 22, 2004·Nature Reviews. Microbiology·Anthony L DeVico, Robert C Gallo
Sep 1, 2004·Cellular Signalling·Martin Oppermann
Sep 15, 2004·The Journal of Experimental Medicine·Jason M BrenchleyDaniel C Douek
Aug 30, 2008·Blood·Jinfang Zhu, William E Paul
Nov 13, 2008·The Journal of Infectious Diseases·Christof GeldmacherMichael Hoelscher
Oct 22, 2009·The New England Journal of Medicine·Supachai Rerks-NgarmUNKNOWN MOPH-TAVEG Investigators
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Adel BenlahrechSteven Patterson
Dec 17, 2009·Nature Reviews. Immunology·Andrew J McMichaelBarton F Haynes
Feb 4, 2010·PLoS Pathogens·Miles P Davenport, Janka Petravic
Apr 14, 2010·Autoimmunity Reviews·Ravi K DineshRam Pyare Singh
Jun 15, 2010·Current Opinion in HIV and AIDS·Nichole R Klatt, Jason M Brenchley
Oct 28, 2010·Current Opinion in HIV and AIDS·Dan H Barouch
Oct 28, 2010·Current Opinion in HIV and AIDS·Giuseppe PantaleoJim Tartaglia
Dec 1, 2010·The Journal of Experimental Medicine·Christof GeldmacherRichard A Koup
Dec 21, 2010·Immunologic Research·Stephanie A FreelGeorgia D Tomaras
Dec 29, 2010·Current HIV/AIDS Reports·Paul R Gorry, Petronela Ancuta
Apr 20, 2011·Current Opinion in HIV and AIDS·Filippos Porichis, Daniel E Kaufmann
Mar 9, 2012·Trends in Immunology·Christof Geldmacher, Richard A Koup
Mar 24, 2012·AIDS·Adrian B McDermott, Richard A Koup
Apr 6, 2012·The New England Journal of Medicine·Barton F HaynesJerome H Kim
Dec 21, 2012·The Journal of Experimental Medicine·Matthieu PerreauGiuseppe Pantaleo
Feb 8, 2013·Cold Spring Harbor Perspectives in Biology·Rob C Hoeben, Taco G Uil
Apr 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nicholas F ParrishBeatrice H Hahn
Jul 11, 2013·Cold Spring Harbor Perspectives in Biology·Bernard Moss
Oct 9, 2013·The New England Journal of Medicine·Scott M HammerUNKNOWN HVTN 505 Study Team
Nov 19, 2013·Cell·Kapil K Saharia, Richard A Koup
Apr 5, 2014·Science·Anthony S FauciSusan P Buchbinder
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Haitao HuSilvia Ratto-Kim
Dec 9, 2014·Human Vaccines & Immunotherapeutics·Hugues Fausther-Bovendo, Gary P Kobinger
Jan 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Diane G CarnathanGuido Silvestri
Jan 30, 2015·AIDS·Marie Patricia DʼSouza, Otto O Yang

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Citations

Aug 14, 2018·Clinical Pharmacology and Therapeutics·Harriet L Robinson
Dec 5, 2018·The Journal of Clinical Investigation·Catia T PercianiKelly S MacDonald
Jul 5, 2019·Expert Review of Vaccines·Jean-Louis Excler, Jerome H Kim
Aug 17, 2020·Archives of Virology·Fatima LaherGlenda E Gray
Sep 12, 2020·Vaccines·Ziyu Wen, Caijun Sun

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Methods Mentioned

BETA
flow cytometry
PCR
PMA

Clinical Trials Mentioned

NCT00223080
NCT00125970

Software Mentioned

FlowJo
TreeStar
GraphPad Prism

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