作者: Rose, Winsley ; Mohan, Venkata Raghava ; Balaji, Veeraraghavan ; Arunachalam, Dilesh Kumar ; Sahai, Nikhil ; Copas, Andrew ; John, Jacob ; Kang, Gagandeep ; Kumar, Praveen ; Abraham, Vinod ; Samuel, Prasanna ; Selwyn, Joshua Anish ; Morris, Tim

BACKGROUNDTyphoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines (TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting.METHODSThe primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants' intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness.DISCUSSIONThe results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines.TRIAL REGISTRATIONClinical Trials Registry of India (CTRI) CTRI/2022/03/041314. Prospectively registered on 23 March 2022 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62548&EncHid=&userName=vellore%20typhoid ). CTRI collects the full WHO Trial Registration Data Set.

2022-11-30·Human Vaccines & Immunotherapeutics3区 · 医学

A multicenter, single-blind, randomized, phase-2/3 study to evaluate immunogenicity and safety of a single intramuscular dose of biological E’s Vi-capsular polysaccharide-CRM ₁₉₇ conjugate typhoid vaccine (TyphiBEV ^TM ) in healthy infants, children, and adults in comparison with a licensed comparator

3区 · 医学

Article

作者: Matur, Ramesh ; Turaga, Kishore ; GV, Subba Reddy ; Paradkar, Vikram ; Thuluva, Subhash

The current scenario of typhoid fever warrants early prevention with typhoid conjugate vaccines in susceptible populations to provide lifelong protection. We conducted a multicenter, single-blind, randomized, Phase 2/3 study to assess the immunogenicity and safety of Biological E's Typhoid Vi-CRM₁₉₇ conjugate vaccine (TyphiBEV^TM) compared to Vi-TT conjugate vaccine manufactured by Bharat Biotech International Limited (Typbar-TCV; licensed comparator) in healthy infants, children, and adults from India. The study's primary objective was to assess the non-inferiority of TyphiBEV^TM in terms of the difference in the proportion of subjects seroconverted with a seroconversion threshold value of ≥2.0 µg/mL against Typbar-TCV. A total of 622 healthy subjects (311 each in both vaccine groups) were randomized and received the single dose of the study vaccine. The TyphiBEV^TM group demonstrated noninferiority compared to the Typbar-TCV group at Day 42. The lower 2-sided 95% confidence interval limit of the group difference was -.34%, which met the non-inferiority criteria of ≥10.0%. The geometric mean concentration (24.79 µg/mL vs. 26.58 µg/mL) and proportion of subjects who achieved ≥4-fold increase in antiVi IgG antibody concentrations (96.95% vs. 97.64%) at Day 42 were comparable between the TyphiBEV^TM and Typbar-TCV vaccine groups. No apparent difference was observed in the safety profile between both vaccine groups. All adverse events reported were mild or moderate in intensity in all age subsets. This data demonstrates that TyphiBEV^TM is non-inferior to TypbarTCV in terms of immunogenicity, and the overall safety and reactogenicity in healthy infants, children, and adults studied from India was comparable.

2021-05-01·Vaccine3区 · 医学

An open-label, comparative, single dose, clinical Phase Ⅰ study to assess the safety and immunogenicity of typhoid conjugate vaccine (Vi-CRM197) in healthy Filipino adults

3区 · 医学

Article

作者: Baik, Yeong Ok ; Yu, Dajung ; Kim, Soo Kyung ; Choi, Seuk Keun ; Kim, Chan Wha ; Yoon, Hyeseon ; Oh, Il Nam ; Lee, Chankyu

An injectable typhoid conjugate vaccine (TCV) provides longer-lasting protection, requires fewer doses, and is suitable for children aged >2 years. In addition, TCV is preferred at most ages owing to its improved immunological properties as it overcomes the limitation of Vi polysaccharide vaccines. Here, we assessed the safety, tolerability, and immunogenicity of a TCV, Vi-CRM197, termed EuTCV, in an open-label clinical phase I study in healthy Filipino adults. This study was conducted in 75 healthy adults aged 18-45 years who were randomized in a 1:1:1 ratio based on the vaccines administered: EuTCV (Test), Typbar-TCV® (WHO prequalified vaccine) and Typhim Vi® (Vi polysaccharide vaccine). The study vaccines were administered at a dose of 25 µg of Vi-CRM197 conjugate by intramuscular injection as a single dose to each of the 25 participants/group, and their immunogenicity and overall safety were assessed for 42 days post-vaccination. All study participants (n = 25/group) completed the trial without dropouts. There were no deaths, SAEs, or events leading to premature withdrawal from the study. Anti-Vi IgG antibody titer (geometric mean titer) of EuTCV group on day 42 was 65.325 [95% CI (36.860, 115.771)], which was significantly higher than that of the WHO prequalified TCV [24.795, 95% CI (16.164, 38.033) p = 0.0055] and the Vi polysaccharide vaccine [7.998, 95% CI (3.800, 16.835) p < 0.0001]. Moreover, the seroconversion rate of EuTCV and Typbar-TCV® was 100%, but that of Typhim Vi® was only 84%. The IgG1-3 subclass titers and serum bactericidal assay results in the EuTCV group showed higher and better bactericidal capacity than the other groups. EuTCV was well tolerated and exhibited an acceptable safety profile in the study population. The Vi-CRM197 conjugate dose of 25 μg may be considered effective in terms of efficacy and safety. ClinicalTrials.gov registration number: NCT03956524.

项与 Vi-CRM197 conjugated vaccine(Biological E) 相关的新闻（医药）

2023-08-21

·PRNewswire

IVI and the Madagascar Institute for Vaccine Research launch typhoid conjugate vaccine campaign for infants and children

ANTANANARIVO, Madagascar, Aug. 21, 2023 /PRNewswire/ -- The International Vaccine Institute (IVI), an international organization with a mission to discover, develop, and deliver safe, effective, and affordable vaccines for global health, and the Madagascar Institute for Vaccine Research (MIVR) at the University of Antanararivo held a ceremony today to launch a mass vaccination campaign against typhoid in the Arivonimamo and Antananarivo-Atsimondrano districts of Madagascar. Continue Reading Prof. Raphael Rakotozandrindrainy, Head of the Madagascar Institute for Vaccine Research and Site Principal Investigator for the TyMA project, receives the first vaccine during the launch ceremony for the TyMA typhoid conjugate vaccine campaign in Antananarivo on August 21, 2023. Credit: Aerie Em/IVI This campaign is a component of the Typhoid Conjugate Vaccine Introduction in Madagascar (TyMA) project, which seeks to evaluate the real-world effectiveness of Vi-CRM197 (trade name TYPHIBEV, manufactured by Biologicals E Limited), a typhoid conjugate vaccine (TCV) pre-qualified by the World Health Organization, in a high-burden setting as a step toward integrating the vaccine into routine vaccination programs in Madagascar. The campaign aims to provide a single dose of Vi-CRM197 to approximately 60,000 children between 9 months and 16 years of age. Dr. Florian Marks, Deputy Director General at IVI and Principal Investigator of the TyMA project, said: "We are thrilled to launch this vaccination campaign to protect children against typhoid with our long-time collaborators at the University of Antanararivo, a pivotal step in our work with the Government of Madagascar to introduce typhoid conjugate vaccine into the national immunization program. IVI's multinational typhoid fever surveillance studies have shown high rates of typhoid in pre-school children in sub-Saharan Africa, including Madagascar, and we strongly believe preventive vaccination will have a significant impact in reducing this burden, especially with the rise of antimicrobial resistance." Prof. Raphael Rakotozandrindrainy, Head of MIVR, University of Antananarivo, and Site Principal Investigator, said: "This typhoid conjugate vaccine campaign is the culmination of a 12-year research collaboration between IVI and MIVR to understand the burden of typhoid fever in Madagascar and bolster clinical surveillance. The campaign will not only protect nearly 60,000 children in Arivonimamo and Antananarivo-Atsimondrano districts but help build an evidence-based case to register TCV in Madagascar. We are grateful for the support of the Ministry of Health in the effort to introduce TCV and look forward to the day all Malagasy infants and children are protected against typhoid." The TyMA TCV campaign follows more than a decade of typhoid fever surveillance in Madagascar and other sub-Saharan African countries through IVI's Typhoid Fever Surveillance in Africa (TSAP) and Severe Typhoid in Africa (SETA) programs, which yielded unprecedented data on the burden of disease in the region. In 2019, Prof. Young-Chul Sung of Pohang University of Science and Technology made a personal donation to IVI through the Korea Support Committee for IVI earmarked to fund vaccination projects in low-income countries. This donation funds the TyMA project, and Prof. Sung attended the campaign launch in Antananarivo. Prof. Young-Chul Sung said, "It has always been my intention that my contribution to IVI would advance efforts to protect children around the world from vaccine-preventable infectious diseases. I am truly honored to attend today's ceremony and witness years of scientific research and collaboration come together to launch a vaccination campaign that will impact the lives of an entire generation of children in Madagascar. I congratulate colleagues at IVI and the University of Antananarivo on reaching this milestone." In addition to generating safety and effectiveness data of Vi-CRM197 specific to a defined population and setting, the TyMA study aims to assess the impact of vaccination on antibiotic use (AMU) and consumption between vaccinated and unvaccinated individuals. With AMU driving the development and spread of bacterial infections resistant to antimicrobial treatments—or, antimicrobial resistance (AMR), this study posits that disease prevention through vaccination may be a safe and effective measure to reduce AMU and AMR. Photo - SOURCE International Vaccine Institute