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Induction of specific antibodies, IgG-secreting plasmablasts and memory B cells following BCG vaccination

By Julia Bitencourt, Morven Wilkie, Marco Polo Peralta Alvarez, Ashley Jacobs, Daniel Wright, Stephanie A Harris, Steven G. Smith, Sean Elias, Andrew White, Sally Sharpe, Matthew K. O'Shea, Helen McShane, Rachel Tanner

Posted 18 Feb 2021
bioRxiv DOI: 10.1101/2021.02.18.431837

Many tuberculosis (TB) vaccine candidates are designed as a boost to BCG; an understanding of the BCG-induced immune response is therefore critical, and the opportunity to relate this to circumstances where BCG does protect may direct the design of more efficacious vaccines. While the T cell response to BCG vaccination has been well-characterised, little is known about the B cell and antibody response. We demonstrate BCG vaccine-mediated induction of specific antibodies in different human populations and macaque species which represent important preclinical models for TB vaccine development. We observe a strong correlation between antibody titres in serum versus plasma with modestly higher titres in serum. We also report for the first time the rapid and transient induction of antibody-secreting plasmablasts following BCG vaccination, together with a robust and durable memory B cell response in humans. Finally, we demonstrate a potential contribution of the antibody response to BCG vaccine-mediated control of mycobacterial growth in vitro. Taken together, our findings indicate that the humoral immune response in the context of BCG vaccination merits further attention to determine whether TB vaccine candidates could benefit from the induction of humoral as well as cellular immunity.

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