Dataset Information

Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition.

ABSTRACT: Undernourished children in low-income countries often exhibit poor responses to oral vaccination. Perturbed microbiota development is linked to undernutrition, but whether and how microbiota changes affect vaccine responsiveness remains unclear. Here, we show that gnotobiotic mice colonized with microbiota from undernourished Bangladeshi children and fed a Bangladeshi diet exhibited microbiota-dependent differences in mucosal IgA responses to oral vaccination with cholera toxin (CT). Supplementation with a nutraceutical consisting of spirulina, amaranth, flaxseed, and micronutrients augmented CT-IgA production. Mice initially colonized with a microbiota associated with poor CT responses exhibited improved immunogenicity upon invasion of bacterial taxa from cagemates colonized with a more "responsive" microbiota. Additionally, a consortium of five cultured bacterial invaders conferred augmented CT-IgA responses in mice fed the supplemented diet and colonized with the "hypo-responsive" community. These results provide preclinical proof-of-concept that diet and microbiota influence mucosal immune responses to CT vaccination and identify a candidate synbiotic formulation.

SUBMITTER: Di Luccia B

PROVIDER: S-EPMC7292785 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition.

Di Luccia Blanda B Ahern Philip P PP Griffin Nicholas W NW Cheng Jiye J Guruge Janaki L JL Byrne Alexandra E AE Rodionov Dmitry A DA Leyn Semen A SA Osterman Andrei L AL Ahmed Tahmeed T Colonna Marco M Barratt Michael J MJ Delahaye Nicolas F NF Gordon Jeffrey I JI

Cell host & microbe 20200428 6

Undernourished children in low-income countries often exhibit poor responses to oral vaccination. Perturbed microbiota development is linked to undernutrition, but whether and how microbiota changes affect vaccine responsiveness remains unclear. Here, we show that gnotobiotic mice colonized with microbiota from undernourished Bangladeshi children and fed a Bangladeshi diet exhibited microbiota-dependent differences in mucosal IgA responses to oral vaccination with cholera toxin (CT). Supplementa ...[more]

PMID: 32348782

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Project description:BACKGROUND: Recent research in two cholera-endemic communities of Zanzibar has shown that a majority (?94%) of the adult population was willing to receive free oral cholera vaccines (OCVs). Since OCV uptake in the 2009 campaign reached only ?50% in these communities, an evaluation of social and cultural factors and of barriers was conducted to understand this difference for future cholera control planning. METHODOLOGY/PRINCIPAL FINDINGS: A random sample of 367 adult peri-urban and rural community residents (46.6% immunized vs. 53.4% unimmunized) was studied with a semi-structured interview that inquired about social and cultural features of cholera depicted in a vignette and barriers to OCV uptake. Symptoms (rectal pain, loose skin only in rural community) and perceived causes (uncovered food, contact with contaminated water) specific for severe diarrhea were associated with uptake. Purchasing drugs from pharmacies to stop diarrhea and vomiting was negatively associated with uptake. Increasing household size, age and previous enteric illness episode were positively related to uptake, the latter only at the rural site. The most prominent barrier to uptake was competing obligations or priorities (reported by 74.5%, identified as most important barrier by 49.5%). Next most prominent barriers were lacking information about the campaign (29.6%, 12.2%), sickness (14.3%, 13.3%) and fear of possible vaccine side effects (15.3%, 5.6%). The majority of unvaccinated respondents requested repetition of the vaccination with free OCVs. CONCLUSIONS/SIGNIFICANCE: Factors associated with uptake indicated a positive impact of the vaccination campaign and of sensitization activities on vaccine acceptance behavior. Unlike communities opposed to cholera control or settings where public confidence in vaccines is lacking, identified barriers to uptake indicated a good campaign implementation and trust in the health system. Despite prospects and demand for repeating the vaccination, local decision-makers should reconsider how careful logistical arrangements may improve community coverage and thus effectiveness of vaccination campaigns.

Project description:Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.

Project description:BackgroundThe World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective.Methodology/principal findingsPublic and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3).Conclusions/significanceBased on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3.

Dataset Information

Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition.

Publications

Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition.

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