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An overview of Vaxchora^TM, a live attenuated oral cholera vaccine.

ABSTRACT: Cholera remains a public health threat among the least privileged populations and regions affected by conflicts and natural disasters. Together with Water, Sanitation and Hygiene practices, use of oral cholera vaccines (OCVs) is a key tool to prevent cholera. Bivalent whole-cell killed OCVs have been extensively used worldwide and found effective in protecting populations against cholera in endemic and outbreak settings. No cholera vaccine had been available for United States (US) travelers at risk for decades until 2016 when CVD 103-HgR (Vaxchora™), an oral live attenuated vaccine, was licensed by the US FDA. A single dose of Vaxchora™ protected US volunteers against experimental challenge 10 days and 3 months after vaccination. However, use of Vaxchora™ poses several challenges in resource poor settings as it requires reconstitution, is age-restricted to 18 to 64 years, has no data in populations endemic for cholera, and faces challenges related to cold chain and cost.

SUBMITTER: Saluja T

PROVIDER: S-EPMC7012186 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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An overview of Vaxchora<sup>TM</sup>, a live attenuated oral cholera vaccine.

Saluja Tarun T Mogasale Vijayalaxmi V VV Excler Jean-Louis JL Kim Jerome H JH Mogasale Vittal V

Human vaccines & immunotherapeutics 20190920 1

Cholera remains a public health threat among the least privileged populations and regions affected by conflicts and natural disasters. Together with Water, Sanitation and Hygiene practices, use of oral cholera vaccines (OCVs) is a key tool to prevent cholera. Bivalent whole-cell killed OCVs have been extensively used worldwide and found effective in protecting populations against cholera in endemic and outbreak settings. No cholera vaccine had been available for United States (US) travelers at r ...[more]

PMID: 31339792

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Project description:Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germfree mice can be colonized and have been used to study OCV immunogenicity. However, germfree animals have impaired immune systems and intestinal physiology; also, live OCVs colonize germfree mice for many months, which does not mimic the clearance kinetics of live OCVs in humans. In this study, we leveraged antibiotic-treated, conventionally raised adult mice to study the effects of transient intestinal colonization by a live OCV V. cholerae strain. In a single-dose vaccination regimen, we found that HaitiV, a live-attenuated OCV candidate, was cleared by streptomycin-treated adult mice within 2 weeks after oral inoculation. This transient colonization elicited far stronger adaptive immune correlates of protection against cholera than did inactivated whole-cell HaitiV. Infant mice from HaitiV-vaccinated dams were also significantly more protected from choleric disease than pups from inactivated-HaitiV-vaccinated dams. Our findings establish the benefits of antibiotic-treated mice for live-OCV studies as well as their limitations and underscore the immunogenicity of HaitiV.IMPORTANCE Oral cholera vaccines (OCVs) are being deployed to combat cholera, but current killed OCVs require multiple doses and show little efficacy in young children. Live OCVs have the potential to overcome these limitations, but small-animal models for testing OCVs have shortcomings. We used an antibiotic treatment protocol for conventional adult mice to study the effects of short-term colonization by a single dose of HaitiV, a live-OCV candidate. Vaccinated mice developed vibriocidal antibodies against V. cholerae and delivered pups that were resistant to cholera, whereas mice vaccinated with inactivated HaitiV did not. These findings demonstrate HaitiV's immunogenicity and suggest that this antibiotic treatment protocol will be useful for evaluating the efficacy of live OCVs.

Project description:Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of Johne's disease (JD) in ruminants, establishes a prolonged and often lifelong enteric infection. The implementation of control measures for bovine JD has faced obstacles due to the considerable expenses involved in disease surveillance and hindered by unreliable and inadequate diagnostic tests, emphasizing the need for an effective vaccine that can stimulate mucosal immunity in the gastrointestinal tract. Previous investigations have demonstrated that deletion of the BacA gene in MAP produces an attenuated strain that can transiently colonize the calf small intestine while retaining its capacity to stimulate systemic immune responses similar to wildtype MAP strains. This study assessed the efficacy of the BacA gene deletion MAP strain, referred to as the BacA vaccine, when administered orally to young calves. The research aimed to evaluate its effectiveness in controlling MAP intestinal infection and to investigate the immune responses elicited by mucosal vaccination. The study represents the first evaluation of an enteric modified live MAP vaccine in the context of an oral MAP challenge in young calves. Oral immunization with BacA reduced MAP colonization specifically in the ileum and ileocecal valve. This partially protective immune response was associated with an increased frequency of CD4+ and CD8+ T cells with a pro-inflammatory phenotype (IFNγ+/TNFα+) in vaccinated animals. Moreover, re-stimulated PBMCs from vaccinated animals showed increased expression of IFNγ, IP-10, IL-2, and IL-17 at 10- and 12-weeks post challenge. Furthermore, immunophenotyping of blood leukocytes revealed that vaccinated calves had increased levels of T cells expressing cell-surface markers consistent with long-term central memory. Overall, our findings provide new insights into the development and immunogenicity of a modified live MAP vaccine against bovine JD, demonstrating oral vaccination can stimulate host immune responses that can be protective against enteric MAP infection.

Project description:Cholera is both an endemic and epidemic disease in many low and middle-income countries (LMICs). Strategies for cholera control include improving water, sanitation, and hygiene; providing early and effective treatment; and deploying oral cholera vaccine (OCV). This last strategy is relatively new, and countries considering its introduction are interested in knowing the potential cost not only of the vaccine, but also the cost of introduction. This paper describes the costing of OCV introduction in LMICs using a publicly available Excel-based tool known as the CholTool. It includes estimates of delivery cost categories which cover not only the service delivery costs (e.g. vaccine procurement, handling, storage, and transport; vaccination administration, monitoring supervision, and field support), but also the programmatic costs associated with introducing a new vaccine (i.e. microplanning, communication and training materials development, sensitization/social mobilization, and personnel training) to ensure that a comprehensive estimate is provided with health payer perspective. CholTool takes the user through a structured sequence of interlinked modules containing input parameter cells (assumptions), decision cells (variable selections), and formulas (calculations) to produce customized cost estimates based on standardized methods. The tool provides both financial and economic cost estimates, to ensure that both costs are available for consideration. Four examples of applications of CholTool are presented in three countries- one in Ethiopia, two in Malawi and one in Nepal. The estimates of economic delivery cost per dose (including service delivery and programmatic costs) were (in USD 2016): $2.89 in Ethiopia, $3.04 in Malawi1, $3.35 in Malawi2 and $3.06 in Nepal. A cost projection conducted before the campaign using the tool and a retrospective costing using the tool in Nepal resulted in no significant difference between economic delivery costs per dose.

Dataset Information

An overview of Vaxchora^TM, a live attenuated oral cholera vaccine.

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An overview of Vaxchora<sup>TM</sup>, a live attenuated oral cholera vaccine.

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Dataset Information

An overview of VaxchoraTM, a live attenuated oral cholera vaccine.

Publications

An overview of Vaxchora<sup>TM</sup>, a live attenuated oral cholera vaccine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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An overview of Vaxchora^TM, a live attenuated oral cholera vaccine.