Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment.
BACKGROUND
Recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. The aim of this study was to assess whether therapeutic immunization could impact the course of Mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, ID93, formulated in a synthetic nanoemulsion adjuvant, GLA-SE, administered in combination with existing first-line chemotherapeutics rifampicin and isoniazid.


METHODS
We used a mouse model of fatal tuberculosis and the established cynomolgus monkey model to design an immuno-chemotherapeutic strategy to increase long-term survival and reduce bacterial burden, compared with standard antibiotic chemotherapy alone.


RESULTS
This combined approach induced robust and durable pluripotent antigen-specific T helper-1-type immune responses, decreased bacterial burden, reduced the duration of conventional chemotherapy required for survival, and decreased M. tuberculosis-induced lung pathology, compared with chemotherapy alone.


CONCLUSIONS
These results demonstrate the ability of therapeutic immunization to significantly enhance the efficacy of chemotherapy against tuberculosis and other infectious diseases, with implications for treatment duration, patient compliance, and more optimal resource allocation.
Infectious Disease Research Institute, Seattle, Washington, USA.
Rhea N
RN
Coler
Sylvie
S
Bertholet
Samuel O
SO
Pine
Mark T
MT
Orr
Valerie
V
Reese
Hillarie Plessner
HP
Windish
Charles
C
Davis
Maria
M
Kahn
Susan L
SL
Baldwin
Steven G
SG
Reed
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D000995:Antitubercular Agents / Q000276:immunology / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000276:immunology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008252:Macaca fascicularis / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*; D055502:Secondary Prevention; D016019:Survival Analysis; D013997:Time Factors; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines; D007538:Isoniazid; D012293:Rifampin