Elsevier

Vaccine

Volume 33, Issue 15, 8 April 2015, Pages 1808-1814
Vaccine

Helicobacter hepaticus infection in BALB/c mice abolishes subunit-vaccine-induced protection against M. tuberculosis

https://doi.org/10.1016/j.vaccine.2015.02.041Get rights and content
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Highlights

  • Neonatal Hh infection of mice upregulates colonic IL10 message.

  • Neonatal Hh infection reduces lung immune responses after immunisation with Ad85A.

  • Protection against Mtb challenge induced by Ad85A is abolished in Hh infected mice.

  • IL10R blockade reverses the effects of Hh infection on Ad85A induced protection.

  • Addition of Hh to the microbiota abolishes protection induced by a subunit vaccine.

Abstract

BCG, the only licensed vaccine against tuberculosis (TB), provides geographically variable protection, an effect ascribed to exposure to environmental mycobacteria (EM). Here we show that altering the intestinal microbiota of mice by early-life infection with the commensal bacterium Helicobacter hepaticus (Hh) increases their susceptibility to challenge with Mycobacterium tuberculosis (Mtb). Furthermore Hh-infected mice immunised parenterally with the recombinant subunit vaccine, human adenovirus type 5 expressing the immunodominant antigen 85A of Mtb (Ad85A), display a reduced lung immune response and protection against Mtb challenge is also reduced. Expression of interleukin 10 (IL10) messenger RNA is increased in the colon of Hh infected mice. Treatment of Hh-infected Ad85A-immunised mice with anti-IL10 receptor antibody, following challenge with Mtb, restores the protective effect of the vaccine. These data show for the first time that alteration of the intestinal microbiota by addition of a single commensal organism can profoundly influence protection induced by a TB subunit vaccine via an IL10-dependent mechanism, a result with implications for the deployment of such vaccines in the field.

Keywords

Microbiota
Subunit vaccine
Tuberculosis
Interleukin 10

Abbreviations

Hh
Helicobacter hepaticus
Mtb
Mycobcterium tuberculosis
CFU
colony forming units

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1

Present address: Respiratory Infection and Airway Disease Infection Section, National Heart & Lung Institute (NHLI), Imperial College London, London, UK.