Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation

Borde, Annika; Larsson, Anette; Holmgren, Jan; Nygren, Erik

doi:10.1016/j.ejpb.2011.06.009

Cited by 14 publications

(4 citation statements)

References 18 publications

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“…A freeze-dried inactivated whole-cell oral cholera vaccine was formulated in attempts to optimize delivery of mass quantities of vaccine to low-income countries [34]. This formulation elicited strong serum and gut mucosal anti-LPS antibody responses in immunized mice; these responses were comparable to those achieved with equivalent liquid formulation [34]. The dry formulation is beneficial in substantially reducing package volumes and weights when delivering product to areas in need of mass vaccination.…”

Section: Discussionmentioning

confidence: 99%

Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing

et al. 2021

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Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit, modified with a C-terminal KDEL endoplasmic reticulum retention motif. EPT has therapeutic potential for ulcerative colitis treatment. Previously, orally administered EPT demonstrated colon epithelial repair activity in dextran sodium sulfate (DSS)-induced acute and chronic colitis in mice. However, the oral dosing requires cumbersome pretreatment with sodium bicarbonate to conserve the acid-labile drug substance while transit through the stomach, hampering its facile application in chronic disease treatment. Here, we developed a solid oral formulation of EPT that circumvents degradation in gastric acid. EPT was spray-dried and packed into enteric-coated capsules to allow for pH-dependent release in the colon. A GM1-capture KDEL-detection ELISA and size-exclusion HPLC indicated that EPT powder maintains activity and structural stability for up to 9 months. Capsule disintegration tests showed that EPT remained encapsulated at pH 1 but was released over 180 min at pH 6.8, the approximate pH of the proximal colon. An acute DSS colitis study confirmed the therapeutic efficacy of encapsulated EPT in C57BL/6 mice upon oral administration without gastric acid neutralization pretreatment compared to vehicle-treated mice (p < 0.05). These results provide a foundation for an enteric-coated oral formulation of spray-dried EPT.

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Section: Discussionmentioning

confidence: 99%

Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing

et al. 2021

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“…While the vaccine decreased the risk of death from cholera by 50% after the first vaccination, it was mostly replaced by the oral vaccines that are currently used 19,20 . Nevertheless, there has been recent interest in developing the cholera vaccine (CV) to overcome the limited immune response of the currently licensed CVs 20‐23 …”

Section: Introductionmentioning

confidence: 99%

“…19,20 Nevertheless, there has been recent interest in developing the cholera vaccine (CV) to overcome the limited immune response of the currently licensed CVs. [20][21][22][23] The present study evaluated the use of chitosan, sodium alginate, and alum as effective adjuvants for the injectable CV to improve the immunological efficacy of the current vaccine produced by VACSERA (Egyptian National Manufacturer of Vaccines).…”

mentioning

confidence: 99%

Chitosan and alginate salt as biomaterials are potential natural adjuvants for killed cholera vaccine

AbdelAllah

Gaber

AbdelGhani

et al. 2021

J Biomedical Materials Res

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Chitosan and alginate salts are natural biopolymers that have gained recent attention in the biomedical sectors. Their properties allow them to become potential candidates as safe, cheap, and effective vaccine adjuvants. The present study aimed to enhance the immunogenic response of a current injectable killed cholera vaccine (KCV) using chitosan and alginate salt as natural adjuvants against alum. We tested KCV adjuvanted with alum, chitosan, and sodium alginate in mice. Mice were immunized intraperitoneally with KCV adjuvanted with alum, chitosan, or alginate salt and compared with a control unadjuvanted immunized group. Humoral, cellular, and functional immune responses were evaluated in all groups. The addition of adjuvants, particularly natural adjuvants, to KCV significantly improved the immune response as demonstrated by specific antibody increase, strong proliferation effects, and high protection rate against different challenge doses of cholera strains. Our findings demonstrate that chitosan and alginate salt are superior adjuvants for boosting the KCV immune response and highlights the requirement for further vaccine development.

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“…Freeze-drying protectants are complex reagents that prevent active component denaturation in vaccines during freeze-drying processes (Hansen et al 2015 ). Under the condition of cold chain logistics, the relatively effective and common formula of cryoprotectants includes monosaccharide, polyalcohol, amino acids, salts and cryoprotectant derivatives (Basu and Domb 2018 ; Borde et al 2011 ; Ohtake et al 2011 ) such as sucrose, phosphate, glutamic acid and albumin (SPGA); lactose, gelatin, sorbitol and HEPES buffer (LGS); potassium phosphate buffer, hydrolysate gelatin and sorbitol (BUGS); and lactose hydrolysate and sucrose (LS) (Chen et al 2012 ; Prabhu et al 2014 ; Zheng et al 2019 ). However, the thermostability and protection of these freeze-drying protectants are unsatisfactory (Siow et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities

et al. 2020

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Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 °C–8 °C. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin (BSA), l -glutamic acid (L-Glu), polyethylene glycol (PEG), and dextran (DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine (rTTV-OVA) and adenovirus vaccine (Ad5-ENV). We compared a panel of five different formulations (PEG: DEX: BSA: L-GLU = 50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3), 50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 °C and 25 °C and that rTTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature.

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Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation

Cited by 14 publications

References 18 publications

Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing

Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing

Chitosan and alginate salt as biomaterials are potential natural adjuvants for killed cholera vaccine

Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities

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