A trivalent recombinant Ad5 gag/pol/nef vaccine fails to protect rhesus macaques from infection or control virus replication after a limiting-dose heterologous SIV challenge.

Vaccine
Matthew R ReynoldsDavid I Watkins

Abstract

It has been suggested that poor immunogenicity may explain the lack of vaccine efficacy in preventing or controlling HIV infection in the Step trial. To investigate this issue we vaccinated eight Indian rhesus macaques with a trivalent replication-incompetent adenovirus serotype 5 vaccine expressing SIV Gag, Pol, and Nef using a regimen similar to that employed in the Step trial. We detected broad vaccine-induced CD8(+) (2-7 pool-specific responses) and CD4(+) (5-19 pool-specific responses) T-cell responses in IFN-γ ELISPOT assays at one week post-boost using fresh PBMC. However, using cryopreserved cells at one and four weeks post-boost we observed a reduction in both the number and magnitude of most vaccine-induced responses. This demonstrates that the time points and conditions chosen to perform immune assays may influence the observed breadth and frequency of vaccine-induced T-cell responses. To evaluate protective efficacy, we challenged the immunized macaques, along with naïve controls, with repeated, limiting doses of the heterologous swarm isolate SIVsmE660. Vaccination did not significantly affect acquisition or control of virus replication in vaccinees compared to naïve controls. Post-infection we observed an average ...Continue Reading

References

Jan 18, 2002·Nature·Jeffrey D Lifson, Malcolm A Martin
Mar 5, 2002·Nature Medicine·Mark B Feinberg, John P Moore
Jun 29, 2002·Science·Brian GaschenBette Korber
Sep 6, 2003·Journal of Immunological Methods·Christian R KreherMagdalena Tary-Lehmann
Jan 30, 2004·Annual Review of Medicine·John W Shiver, Emilio A Emini
Jun 1, 2006·The Journal of Experimental Medicine·Joseph J MattapallilMario Roederer
May 1, 2007·PLoS Computational Biology·David C NickleNebojsa Jojic
Jun 1, 2007·Journal of Virology·John T LoffredoDavid I Watkins
Jun 7, 2007·JAMA : the Journal of the American Medical Association·John W MellorsAlvaro Muñoz
Aug 21, 2007·Journal of Immunological Methods·Rachel E OwenPhilip J Norris
Jan 16, 2008·The Journal of Experimental Medicine·Rafick-Pierre Sekaly
Apr 3, 2008·Human Vaccines·Fusheng LiSteven G Self
Apr 25, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Frances H PriddyUNKNOWN Merck V520-016 Study Group
Jun 7, 2008·Nature Medicine·David I WatkinsWayne C Koff
Jul 26, 2008·Science·Anthony S FauciWarner C Greene
Oct 8, 2008·The Journal of Experimental Medicine·Matthew R ReynoldsDavid I Watkins
Dec 4, 2008·AIDS·Lawrence CoreyJames G Kublin
Apr 29, 2009·Biometrics·Michael G Hudgens, Peter B Gilbert
Jul 14, 2009·The Journal of Infectious Diseases·Michael G HudgensSteven G Self
Oct 22, 2009·The New England Journal of Medicine·Supachai Rerks-NgarmUNKNOWN MOPH-TAVEG Investigators
Oct 28, 2010·Current Opinion in HIV and AIDS·Dan H Barouch
Feb 1, 2011·The Journal of Infectious Diseases·Jacques FellayUNKNOWN NIAID HIV Vaccine Trials Network

❮ Previous
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Citations

Oct 3, 2012·Retrovirology·Per Johan Klasse, John P Moore
Jul 23, 2013·Retrovirology·Torben SchiffnerLucy Dorrell
Oct 24, 2014·Annual Review of Medicine·Jerome H KimNelson L Michael
Dec 10, 2015·Expert Review of Vaccines·Anna-Lise Williamson, Edward P Rybicki
Jun 24, 2015·Vaccine·Jean-Louis ExclerJerome H Kim
Nov 25, 2014·Cell·Dan H Barouch, Nelson L Michael
Nov 23, 2015·American Journal of Preventive Medicine·Jean-Louis ExclerJerome H Kim
Sep 18, 2012·Critical Reviews in Microbiology·Derrick LouzRob C Hoeben
Mar 19, 2014·Human Vaccines & Immunotherapeutics·Jean-Louis ExclerJerome H Kim
Aug 19, 2016·Current Opinion in HIV and AIDS·Jean-Louis Excler, Nelson L Michael
Feb 11, 2014·Current Protocols in Immunology·Yongjun SuiJay A Berzofsky
Dec 12, 2018·Expert Review of Vaccines·Mohammad Arif Rahman, Marjorie Robert-Guroff
May 15, 2013·Current Opinion in HIV and AIDS·Christine M Fennessey, Brandon F Keele
Nov 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shari N GordonGenoveffa Franchini
Feb 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amelia K HajDavid H O'Connor
Sep 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shari N GordonGenoveffa Franchini
Nov 17, 2020·Frontiers in Immunology·Jason T WeinfurterMatthew R Reynolds

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