Immunological and physical evaluation of the multistage tuberculosis subunit vaccine candidate H56/CAF01 formulated as a spray-dried powder |
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| Institution: | 1. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark;2. Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark;1. AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Hong Kong SAR, PR China;2. HKU AIDS Institute Shenzhen Research Laboratory and Guangdong Key Laboratory for Emerging Infectious Disease, Shenzhen Third People''s Hospital, Guangdong Medical College, Shenzhen, PR China;3. Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, PR China;1. Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China;2. Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;3. Centre for Biologicals Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario, Canada;1. Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark;2. Veterinary Sciences Centre, School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland;3. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;1. Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong Special Administrative Region;2. Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, Pharmacy and Bank Building A15, The University of Sydney, NSW, 2006, Australia;3. The University of Hong Kong Shenzhen Institute of Research and Innovation, 5/F, Key Laboratory Platform Building, Shenzhen 518057, China |
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| Abstract: | Liquid vaccine dosage forms have limited stability and require refrigeration during their manufacture, distribution and storage. In contrast, solid vaccine dosage forms, produced by for example spray drying, offer improved storage stability and reduced dependence on cold-chain facilities. This is advantageous for mass immunization campaigns for global public health threats, e.g., tuberculosis (TB), and offers cheaper vaccine distribution. The multistage subunit vaccine antigen H56, which is a fusion protein of the Mycobacterium tuberculosis (Mtb) antigens Ag85B, ESAT-6, and Rv2660, has been shown to confer protective efficacy against active TB before and after Mtb exposure in preclinical models, and it is currently undergoing clinical phase 2a testing. In several studies, including a recent study comparing multiple clinically relevant vaccine adjuvants, the T helper type 1 (Th1)/Th17-inducing adjuvant CAF01 was the most efficacious adjuvant for H56 to stimulate protective immunity against Mtb. With the long-term goal of designing a thermostable and self-administrable dry powder vaccine based on H56 and CAF01 for inhalation, we compared H56 spray-dried with CAF01 with the non-spray-dried H56/CAF01 vaccine with respect to their ability to induce systemic Th1, Th17 and humoral responses after subcutaneous immunization. Here we show that spray drying of the H56/CAF01 vaccine results in preserved antigenic epitope recognition and adjuvant activity of CAF01, and the spray-dried, reconstituted vaccine induces antigen-specific Th1, Th17 and humoral immune responses, which are comparable to those stimulated by the non-spray-dried H56/CAF01 vaccine. In addition, the spray-dried and reconstituted H56/CAF01 vaccine promotes similar polyfunctional CD4+ T-cell responses as the non-spray-dried vaccine. Thus, our study provides proof-of-concept that spray drying of the subunit vaccine H56/CAF01 preserves vaccine-induced humoral and cell-mediated immune responses. These results support our ongoing efforts to develop a thermostable, dry powder-based TB vaccine. |
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| Keywords: | Tuberculosis Vaccine H56 CAF01 Spray drying Th1/Th17 |
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