The Euvichol story – Development and licensure of a safe, effective and affordable oral cholera vaccine through global public private partnerships

Odevall, Lina,Hong, Deborah,Digilio, Laura,Sahastrabuddhe, Sushant,Mogasale, Vittal,Baik, Yeongok,Choi, Seukkeun,Kim, Jerome H.,Lynch, Julia Elsevier Science 2018 Vaccine Vol.36 No.45

<P>Cholera, a diarrheal disease primarily affecting vulnerable populations in developing countries, is estimated to cause disease in more than 2.5 million people and kill almost 100,000 annually. An oral cholera vaccine (OCV) has been available globally since 2001; the demand for this vaccine from affected countries has however been very low, due to various factors including vaccine price and mode of administration. The low demand for the vaccine and limited commercial incentives to invest in research and development of vaccines for developing country markets has kept the global supply of OCVs down. Since 1999, the International Vaccine Institute has been committed to make safe, effective and affordable OCVs accessible. Through a variety of partnerships with collaborators in Sweden, Vietnam, India and South Korea, and with public and private funding, IVI facilitated development and production of two affordable and WHO-prequalified OCVs and together with other stakeholders accelerated the introduction of these vaccines for the global public-sector market.</P>

Ecosystemic Resilience Relative to an Increasing Population of Unwed Mothers in Korea

강혜성,Sandra A. Rigazio-DiGilio 한국건강심리학회 2023 한국심리학회지 건강 Vol.28 No.2

Despite positive changes in the cultural notion of unwed mothers in Korea, they still experience numerous challenges in their child-rearing efforts. In this research, we explored unwed mothers’ experiences and perceptions about their own resilience in wider contexts and the facilitative factors that may contribute to it through interviews and community genograms. Participants included 18 unwed mothers raising one or more children with the youngest child aged 0–6 years. Results revealed six themes in which these mothers drew on their resources to overcome challenges when navigating new social contexts as unwed mothers. Based on these findings, we proposed the Korean Unwed Mothers’ Ecosystemic Resilience model to conceptualize resilience and its facilitative factors. Implications on social programs and policies, as well as implications for the training of and support for counselors and health professionals, are discussed.

Use of oral cholera vaccine as a vaccine probe to define the geographical dimensions of person-to-person transmission of cholera

Ali, Mohammad,Kim, Deok Ryun,Kanungo, Suman,Sur, Dipika,Manna, Byomkesh,Digilio, Laura,Dutta, Shanta,Marks, Florian,Bhattacharya, Sujit K.,Clemens, John Elsevier 2018 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Vol.66 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Cholera is known to be transmitted from person to person, and inactivated oral cholera vaccines (OCVs) have been shown to confer herd protection via interruption of this transmission. However, the geographic dimensions of chains of person-to-person transmission of cholera are uncertain. The ability of OCVs to confer herd protection was used to define these dimensions in two cholera-endemic settings, one in rural Bangladesh and the other in urban India.</P> <P><B>Methods</B></P> <P>Two large randomized, placebo-controlled trials of inactivated OCVs, one in rural Matlab, Bangladesh and the other in urban Kolkata, India, were reanalyzed. Vaccine herd protection was evaluated by relating the risk of cholera in placebo recipients to vaccine coverage of surrounding residents residing within concentric rings. In Matlab, concentric rings in 100-m increments up to 700m were evaluated; in Kolkata, 50-m increments up to 350m were evaluated.</P> <P><B>Results</B></P> <P>One hundred and eight cholera cases among 24667 placebo recipients were detected during 1year of post-vaccination follow-up at Matlab; 128 cholera cases among 34968 placebo recipients were detected during 3 years of follow-up in Kolkata. Consistent inverse relationships were observed between vaccine coverage of the ring and the risk of cholera in the central placebo recipient for rings with radii up to 500m in Matlab and up to 150m in Kolkata.</P> <P><B>Conclusions</B></P> <P>These results suggest that the dimensions of chains of person-to-person transmission in endemic settings can be quite large and may differ substantially from setting to setting. Using OCVs as ‘probes’ to define these dimensions can inform geographical targeting strategies for the deployment of these vaccines in endemic settings.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cholera, a waterborne disease, is known to be transmitted from person to person. </LI> <LI> However, the geographical dimensions of this transmission are uncertain. </LI> <LI> Oral cholera vaccines were used as probes to define these dimensions. </LI> <LI> Dimensions were 500m in rural Bangladesh and 150m in Kolkata, India. </LI> <LI> Person-to-person transmission of cholera can be sustained over long distances. </LI> </UL> </P>

Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis

Bi, Qifang,Ferreras, Eva,Pezzoli, Lorenzo,Legros, Dominique,Ivers, Louise C,Date, Kashmira,Qadri, Firdausi,Digilio, Laura,Sack, David A,Ali, Mohammad,Lessler, Justin,Luquero, Francisco J,Azman, Andrew Elsevier Science ;, The Lancet Pub. Group 2017 LANCET INFECTIOUS DISEASES Vol.17 No.10

<P><B>Summary</B></P><P><B>Background</B></P><P>Killed whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature.</P><P><B>Methods</B></P><P>For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232.</P><P><B>Findings</B></P><P>Seven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, <I>I</I><SUP>2</SUP>=58%) and effectiveness of 76% (62–85, <I>I</I><SUP>2</SUP>=0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15–42], <I>I</I><SUP>2</SUP>=0%) was lower than in those 5 years or older (64% [58–70], <I>I</I><SUP>2</SUP>=0%; p<0·0001). Two-dose efficacy estimates of kOCV were similar during the first 2 years after vaccination, with estimates of 56% (95% CI 42–66, <I>I</I><SUP>2</SUP>=45%) in the first year and 59% (49–67, <I>I</I><SUP>2</SUP>=0) in the second year. The efficacy reduced to 39% (13 to 57, <I>I</I><SUP>2</SUP>=48%) in the third year, and 26% (−46 to 63, <I>I</I><SUP>2</SUP>=74%) in the fourth year.</P><P><B>Interpretation</B></P><P>Two kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control.</P><P><B>Funding</B></P><P>The Bill & Melinda Gates Foundation.</P>

A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines ^☆

Russo, Paola,Ligsay, Antonio D.,Olveda, Remigio,Choi, Seuk Keun,Kim, Deok Ryun,Park, Ju Yeon,Park, Ju Yeong,Syed, Khalid Ali,Dey, Ayan,Kim, Yang Hee,Lee, Sung Hee,Kim, Jayoung,Chon, Yun,Digilio, Laura Elsevier Science 2018 Vaccine Vol.36 No.29

<▼1><P><B>Highlights</B></P><P>•<P>Bridging study demonstrating the equivalence of two variations of Euvichol®.</P>•<P>The 600L thimerosal-free Euvichol® is safe and immunogenic in adults and children.</P>•<P>The scale-up of Euvichol® allows expanding global access to oral cholera vaccine.</P></P></▼1><▼2><P><B>Background</B></P><P>To contribute to the global demand for oral cholera vaccine (OCV), the production of Euvichol® was scaled up with elimination of thimerosal. To demonstrate the equivalence of the variations, a study was carried out in the Philippines.</P><P><B>Methods</B></P><P>Healthy male and female adults and children in Manila were randomized to receive two doses of Euvichol® two weeks apart from either the 100L (Comparator) or the 600L (Test) variation. Primary and secondary immunogenicity endpoints were respectively geometric mean titer (GMT) of vibriocidal antibodies (two weeks post second dose) and seroconversion rate (two weeks after each dose) against O1 Inaba, Ogawa, and O139 serogroups. The GMT of vibriocidal antibodies against O1 Inaba, Ogawa, and O139 two weeks post first dose was also measured. To show the equivalence of two variations of Euvichol®, the ratio of GMT and the difference of seroconversion rate between Test and Comparator vaccines were tested with equivalence margin of [0.5, 2.0] for GMT ratio and of 15% for seroconversion rate, respectively. Safety assessment included solicited reactogenicity within 6 days after each dose and unsolicited and serious adverse events.</P><P><B>Results</B></P><P>A total of 442 participants were enrolled. For the overall population, equivalence between Test and Comparator was demonstrated for vibriocidal antibody response against O1 Inaba and Ogawa serotypes and O139 serogroup in both modified intention-to-treat (mITT) and per protocol analysis, since the 95% confidence intervals (CI) of GMT to any serotypes were within the lower and upper boundary [0.5, 2.0]. Seroconversion rates after two doses also showed equivalence for O1 Inaba, Ogawa, and O139. The vaccine was safe and well tolerated, similarly between the two groups.</P><P><B>Conclusion</B></P><P>The study results support the equivalence of the 600L Euvichol® to the 100L formulation in healthy children and adults. The 600L Euvichol® is safe and immunogenic in adults and children.</P><P>ClinicalTrials.gov registration number: NCT02502331.</P></▼2>