A thermostable, dry formulation inactivated Hikojima whole cell/cholera toxin B subunit oral cholera vaccine. Issue 21 (16th May 2023)

• Record Type: Journal Article
• Authors: Terrinoni, Manuela; Nordqvist, Stefan L.; Löfstrand, Madeleine; Nilsson, Frida; Källgård, Susanne; Sharma, Tarun; Lebens, Michael R.; Holmgren, Jan
• Is Part Of: Vaccine. Volume 41:Issue 21(2023)
• Page Start: 3347
• Page End: 3357
• Publication Date: 2023-05-16
• Subjects: Cholera vaccine -- Cholera B subunit -- Thermostability -- Dry formulation -- Mucosal immunity; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2023.04.004
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Development of an improved, thermostable dry formulation oral cholera vaccine (OCV). Contains lyophilized formalin inactivated cholera bacteria and cholera toxin B subunit. Single strain bacteria and high-yield CTB ensure low-cost manufacturing. Proven stability for at least 26 months at 25 °C and 8 months at 40 °C. Tolerability and immunogenicity equivalent to current, more complex, thermolabile liquid OCVs. Abstract: The feared diarrheal disease cholera remains an important global health problem. Use of oral cholera vaccine (OCV) from a global stockpile against both epidemic and endemic cholera is a cornerstone in the World Health Organisations (WHOs) global program for "Ending cholera by 2030". Three liquid inactivated whole-cell OCVs (Dukoral®, Shanchol TM, and Euvichol-Plus®) are WHO prequalified and have proved to be safe and effective. However, their multicomponent composition and cold-chain requirement increase manufacturing, storage and transport costs. Shanchol TM and Euvichol-Plus® OCVs used in WHOs global vaccine stockpile also lack the protective cholera toxin B-subunit (CTB) antigen present in Dukoral®, which results in suboptimal efficacy. WHOs Global Task Force on Cholera Control (GTFCC) has identified a thermostable, dry formulation vaccine as a priority for further OCV development. We describe here the development of such a vaccine, based on a lyophilized mixture of a single strain of formalin-killed Hikojima bacteria together with a low-cost, recombinantly produced CTB. The new vaccine, which is easy and inexpensive to manufacture, could be stored for at least 26 months at 25 °C and for at least 8 months at 40 °C with preservation of cell morphology and with no loss of protective Ogawa and Inaba lipopolysaccharides or CTB. It also proved to be well tolerated and to have equivalent oral immunogenicity in mice as Shanchol TM and Dukoral® OCVs with regard to both serum and intestinal-mucosal antibody responses.