Mycobacterium tuberculosis proteins involved in cell wall lipid biosynthesis improve BCG vaccine efficacy in a murine TB model.
OBJECTIVE
Advances in tuberculosis (TB) vaccine development are urgently required to enhance global disease management. We evaluated the potential of Mycobacterium tuberculosis (M. tb)-derived protein antigens Rv0447c, Rv2957 and Rv2958c to boost BCG vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) adjuvant.


METHODS
Mice received the BCG vaccine, followed by Rv0447c, Rv2957 and Rv2958c protein boosting with or without GLA-SE adjuvant 3 and 6 weeks later. Immune responses were examined at given time points. 9 weeks post vaccination, mice were aerosol-challenged with M. tb, and sacrificed at 6 and 12 weeks to assess bacterial burden.


RESULTS
Vaccination of mice with BCG and M. tb proteins in the presence of GLA-SE adjuvant triggered strong IFN-γ and IL-2 production by splenocytes; more TNF-α was produced without GLA-SE addition. Antibody responses to all three antigens did not differ, with or without GLA-SE adjuvant. Protein boosting without GLA-SE adjuvant resulted in vaccinated animals having better control of pulmonary M. tb load at 6 and 12 weeks post aerosol infection, while animals receiving the protein boost with GLA-SE adjuvant exhibited more bacteria in the lungs.


CONCLUSIONS
Our data provides evidence for developing Rv2958c, Rv2957 and Rv0447c in a heterologous prime-boost vaccination strategy with BCG.
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.
Martin
M
Rao
AERAS TB Vaccines, Rockville, Maryland, USA.
Nathalie
N
Cadieux
AERAS TB Vaccines, Rockville, Maryland, USA.
Megan
M
Fitzpatrick
Infectious Disease Research Institute (IDRI), Seattle, USA.
Steven
S
Reed
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.
Sergei
S
Arsenian
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden.
Davide
D
Valentini
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.
Shreemanta
S
Parida
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.
Ernest
E
Dodoo
Division of Infection and Immunity, University College London and the NIHR Biomedical Research centre at UCL Hospitals NHS Foundation Trust London, UK.
Alimuddin
A
Zumla
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: Markus.Maeurer@ki.se.
Markus
M
Maeurer
D000276:Adjuvants, Immunologic; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002473:Cell Wall / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control; D064166:Vaccine Potency
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D008055:Lipids
Bacille Calmette-Guérin; Mycobacterium tuberculosis; T cells; antibodies; antigens; tuberculosis; vaccines