A Randomized, Controlled Safety, and Immunogenicity Trial of the M72/AS01 Candidate Tuberculosis Vaccine in HIV-Positive Indian Adults

Medicine
Nagalingeswaran KumarasamyOpokua Ofori-Anyinam

Abstract

Human immunodeficiency virus (HIV)-associated tuberculosis is a major public health threat. We evaluated the safety and immunogenicity of the candidate tuberculosis vaccine M72/AS01 in HIV-positive and HIV-negative Indian adults.Randomized, controlled observer-blind trial (NCT01262976).We assigned 240 adults (1:1:1) to antiretroviral therapy (ART)-stable, ART-naive, or HIV-negative cohorts. Cohorts were randomized 1:1 to receive M72/AS01 or placebo following a 0, 1-month schedule and followed for 12 months (time-point M13). HIV-specific and laboratory safety parameters, adverse events (AEs), and M72-specific T-cell-mediated and humoral responses were evaluated.Subjects were predominantly QuantiFERON-negative (60%) and Bacille Calmette-Guérin-vaccinated (73%). Seventy ART-stable, 73 ART-naive, and 60 HIV-negative subjects completed year 1. No vaccine-related serious AEs or ART-regimen adjustments, or clinically relevant effects on laboratory parameters, HIV-1 viral loads or CD4 counts were recorded. Two ART-naive vaccinees died of vaccine-unrelated diseases. M72/AS01 induced polyfunctional M72-specific CD4 T-cell responses (median [interquartile range] at 7 days postdose 2: ART-stable, 0.9% [0.7-1.5]; ART-naive, 0.5% [0.2-1.0]; ...Continue Reading

References

Mar 11, 2000·The Journal of Clinical Investigation·J M McCuneM Hellerstein
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K Murali-Krishna, R Ahmed
Aug 22, 2000·The Journal of Experimental Medicine·A W GoldrathM J Bevan
Jul 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohamed ElrefaeiHuyen Cao
Apr 21, 2007·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Joel Fleury Djoba SiawayaGerhard Walzl
Oct 13, 2007·Expert Review of Vaccines·Nathalie GarçonMarcelle Van Mechelen
Jun 12, 2008·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Alessandra ViganòMario Clerici
Feb 4, 2010·The Journal of Infectious Diseases·Judith R GlynnPam Sonnenberg
Apr 17, 2010·American Journal of Respiratory and Critical Care Medicine·C Robert HorsburghC Fordham von Reyn
Apr 20, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Haileyesus GetahunPaul Nunn
Jun 8, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Douglas S Kernodle
Jul 10, 2010·AIDS·Pablo TebasUNKNOWN Center for AIDS Research and Clinical Trials Unit of the University of Pennsylvania
Apr 22, 2011·Expert Review of Vaccines·Nathalie Garçon, Marcelle Van Mechelen
Mar 1, 2012·PLoS Pathogens·Andrzej PawlowskiGunilla Källenius
Apr 18, 2012·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·C F von ReynS Egwaga
Jan 12, 2013·American Journal of Respiratory and Critical Care Medicine·Cheryl L DayWillem A Hanekom
Mar 8, 2013·Advances in Experimental Medicine and Biology·Lee KozakiewiczJohn Chan
Mar 19, 2013·Cell Host & Microbe·Jacqueline M Achkar, Arturo Casadevall
Mar 26, 2013·Parasites & Vectors·Xin-Xu Li, Xiao-Nong Zhou
Feb 6, 2014·PloS One·Michele TamerisThomas J Scriba
Nov 28, 2014·Microbiology and Molecular Biology Reviews : MMBR·Thomas R HawnSteven G Self
Apr 29, 2015·Seminars in Immunopathology·Philana Ling Lin, JoAnne L Flynn

❮ Previous
Next ❯

Citations

Aug 7, 2018·Current Opinion in HIV and AIDS·Elisa NemesMark Hatherill
Aug 15, 2019·Microorganisms·Erica StewartNikolai Petrovsky
Feb 16, 2020·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Junli LiChuan Qin
Jul 14, 2017·Pneumonia·James A Triccas, Claudio Counoupas
Oct 4, 2018·The New England Journal of Medicine·Olivier Van Der MeerenDereck R Tait
Oct 21, 2017·Frontiers in Immunology·Deborah A LewinsohnThomas J Scriba
Mar 5, 2019·F1000Research·Lewis K SchragerJohan Vekemans
Feb 23, 2020·Frontiers in Microbiology·Mark HatherillThomas R Hawn
Oct 30, 2019·The New England Journal of Medicine·Dereck R TaitFrançois Roman
Oct 22, 2020·NPJ Vaccines·Riti Sharan, Deepak Kaushal
Jan 21, 2021·Cells·Ana Rita Franco, Francesco Peri
May 18, 2020·Trends in Microbiology·Riti SharanDeepak Kaushal
Mar 27, 2021·Human Vaccines & Immunotherapeutics·Thomas ChoVishwanath Venketaraman

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
enzyme-linked immunosorbent assay

Clinical Trials Mentioned

NCT01262976

Software Mentioned

YRG CARE
SASv8
FlowJo

Related Concepts

Related Feeds

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.