Nonclinical Development of BCG Replacement Vaccine Candidates

Vaccines
Kamalakannan VelmuruganMichael J Brennan

Abstract

The failure of current Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacteriu...Continue Reading

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Citations

Jun 26, 2013·Human Vaccines & Immunotherapeutics·David A Hokey, Ann Ginsberg
Mar 31, 2018·Human Vaccines & Immunotherapeutics·Wenping GongXueqiong Wu
Dec 16, 2016·Clinical and Vaccine Immunology : CVI·André G LoxtonUNKNOWN VPM Study Group
Apr 8, 2014·Expert Review of Vaccines·Stefan He KaufmannGerhard Walzl
Feb 16, 2020·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Junli LiChuan Qin
Sep 30, 2020·Disease Models & Mechanisms·Laylaa RamosMercedes Gonzalez-Juarrero
Oct 5, 2017·Frontiers in Immunology·Natalie E NieuwenhuizenStefan H E Kaufmann
Mar 20, 2020·Seminars in Immunopathology·Benedict Brazier, Helen McShane
Nov 2, 2019·Clinical Microbiology Reviews·Suraj B SableThomas J Scriba
Oct 22, 2020·NPJ Vaccines·Riti Sharan, Deepak Kaushal
Jan 15, 2017·Microbiology Spectrum·Mark HatherillHelen McShane

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Methods Mentioned

BETA
genetic modifications
PCR

Software Mentioned

FlowJo
Aeras

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