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.
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.
Authors: Austin Pantel; Cheolho Cheong; Durga Dandamudi; Elina Shrestha; Saurabh Mehandru; Luke Brane; Darren Ruane; Angela Teixeira; Leonia Bozzacco; Ralph M Steinman; M Paula Longhi Journal: Eur J Immunol Date: 2011-12-12 Impact factor: 5.532
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Authors: Y A Skeiky; P J Ovendale; S Jen; M R Alderson; D C Dillon; S Smith; C B Wilson; I M Orme; S G Reed; A Campos-Neto Journal: J Immunol Date: 2000-12-15 Impact factor: 5.422
Authors: G P Walsh; E V Tan; E C dela Cruz; R M Abalos; L G Villahermosa; L J Young; R V Cellona; J B Nazareno; M A Horwitz Journal: Nat Med Date: 1996-04 Impact factor: 53.440
Authors: Susan L Baldwin; Valerie A Reese; Po-Wei D Huang; Elyse A Beebe; Brendan K Podell; Steven G Reed; Rhea N Coler Journal: Clin Vaccine Immunol Date: 2015-12-09
Authors: Crystal A Shanley; Gregory C Ireton; Susan L Baldwin; Rhea N Coler; Steven G Reed; Randall J Basaraba; Ian M Orme Journal: Tuberculosis (Edinb) Date: 2013-09-07 Impact factor: 3.131
Authors: Mark T Orr; Christopher B Fox; Susan L Baldwin; Sandra J Sivananthan; Elyse Lucas; Susan Lin; Tony Phan; James J Moon; Thomas S Vedvick; Steven G Reed; Rhea N Coler Journal: J Control Release Date: 2013-08-09 Impact factor: 9.776
Authors: Bianca R Mothé; Cecilia S Lindestam Arlehamn; Courtney Dow; Myles B C Dillon; Roger W Wiseman; Patrick Bohn; Julie Karl; Nadia A Golden; Trey Gilpin; Taylor W Foreman; Mark A Rodgers; Smriti Mehra; Thomas J Scriba; JoAnne L Flynn; Deepak Kaushal; David H O'Connor; Alessandro Sette Journal: Tuberculosis (Edinb) Date: 2015-08-28 Impact factor: 3.131