Adjuvant formulation structure and composition are critical for the development of an effective vaccine against tuberculosis

JOURNAL OF CONTROLLED RELEASE

卷:172

Article

Orr, Mark T.¹  Fox, Christopher B.¹  Baldwin, Susan L.¹  Sivananthan, Sandra J.¹  Lucas, Elyse¹  Lin, Susan¹  Phan, Tony¹  Moon, James J.^2,3,4  Vedvick, Thomas S.¹  Reed, Steven G.¹  Coler, Rhea N.¹ 

[1] Infect Dis Res Inst, Seattle, WA 98104 USA

[2] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA

[3] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA 02129 USA

[4] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

关键词: Vaccine formulation;    Liposomes;    Oil-in-water emulsions;    Alum;    Mycobacterium tuberculosis;   

DOI  :  10.1016/j.jconrel.2013.07.030

来源: Elsevier

【 摘 要 】

One third of the world is infected with Mycobacterium tuberculosis (Mtb) with eight million new cases of active tuberculosis (TB) each year. Development of a new vaccine to augment or replace the only approved TB vaccine, BCG, is needed to control this disease. Mtb infection is primarily controlled by TH1 cells through the production of IFN-gamma and TNF which activate infected macrophages to kill the bacterium. Here we examine an array of adjuvant formulations containing the TLR4 agonist GLA to identify candidate adjuvants to pair with ID93, a lead TB vaccine antigen, to elicit protective TH1 responses. We evaluate a variety of adjuvant formulations including alum, liposomes, and oil-in-water emulsions to determine how changes in formulation composition alter adjuvant activity. We find that alum and an aqueous nanosuspension of GLA synergize to enhance generation of ID93-specific TH1 responses, whereas neither on their own are effective adjuvants for generation of ID93-specific TH1 responses. For GLA containing oil-in-water emulsions, the selection of the oil component is critical for adjuvant activity, whereas a variety of lipid components may be used in liposomal formulations of GLA. The composition of the liposome formulation of ID93/GLA does alter the magnitude of the TH1 response. These results demonstrate that there are multiple solutions for an effective formulation of a novel TB vaccine candidate that enhances both TH1 generation and protective efficacy. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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