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From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD).

ABSTRACT: Hand, foot, and mouth disease (HFMD) recently emerged as a global public threat. The licensure of inactivated enterovirus A71 (EV-A71) vaccine was the first step in using a vaccine to control HFMD. New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage. The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines. The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes. The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a cross-protective antibody response.

SUBMITTER: He X

PROVIDER: S-EPMC7525078 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD).

He Xiangchuan X Zhang Miaomiao M Zhao Chen C Zheng Peiyong P Zhang Xiaoyan X Xu Jianqing J

Virologica Sinica 20200930 2

Hand, foot, and mouth disease (HFMD) recently emerged as a global public threat. The licensure of inactivated enterovirus A71 (EV-A71) vaccine was the first step in using a vaccine to control HFMD. New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage. The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines. The development of multivalent vaccines was attempted via the simple ...[more]

PMID: 32997323

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Project description:ObjectivesEnterovirus 71 (EV71) and coxsackievirus A16 (CA16) were responsible for 43.3% (235 123/543 243) and 24.8% (134 607/543 243) of all laboratory-confirmed hand, foot and mouth disease (HFMD) cases during 2010-2015 in China. Three monovalent EV71 vaccines have been licensed in China while bivalent EV71/CA16 vaccines are under development. A comparative cost-effectiveness analysis of bivalent EV71/CA16 versus monovalent EV71 vaccination would be useful for informing the additional value of bivalent HFMD vaccines in China.MethodsWe used a static model parameterized with the national HFMD surveillance data during 2010-2013, virological HFMD surveillance records from all 31 provinces in mainland China during 2010-2013 and caregiver survey data of costs and health quality of life during 2012-2013. We estimated the threshold vaccine cost (TVC), defined as the maximum additional cost that could be paid for a cost-effective bivalent EV71/CA16 vaccine over a monovalent EV71 vaccine, as the outcome. The base case analysis was performed from a societal perspective. Several sensitivity analyses were conducted by varying assumptions governing HFMD risk, costs, discounting and vaccine efficacy.ResultsIn the base case, choosing the bivalent EV71/CA16 over monovalent EV71 vaccination would be cost-effective only if the additional cost of the bivalent EV71/CA16 compared with the monovalent EV71 vaccine is less than €4.7 (95% CI 4.2-5.2). Compared with the TVC in the base case, TVC increased by up to €8.9 if all the test-negative cases were CA16-HFMD; decreased by €1.1 with an annual discount rate of 6% and exclusion of the productivity loss; and increased by €0.14 and €0.3 with every 1% increase in bivalent vaccine efficacy against CA16-HFMD and differential vaccine efficacy against EV71-HFMD, respectively.ConclusionsBivalent EV71/CA16 vaccines can be cost-effective compared with monovalent EV71 vaccines, if suitably priced. Our study provides further evidence for determining the optimal use of HFMD vaccines in routine paediatric vaccination programme in China.

Project description:Hand, foot and mouth disease (HFMD) is a common childhood infectious disease, caused by enteroviruses (EVs), which can present with typical or atypical lesions. The illness is self-limiting, but it can also have serious complications. Since 1997, HFMD infections have become endemic and have increased to epidemic proportions across the Asia Pacific region, including India. Coxsackievirus-A16 (CV-A16) outbreaks occurred in India from 2005 onwards, although the clinical symptoms were noticeably different during this period. Understanding the population dynamics of enteroviruses that cause HFMD is crucial in the post-polio era because one of the circulating strain may replace another as the dominant strain. The aim of this study is to describe the genetic features of the CV-A16 strains isolated from hand, foot and mouth disease (HFMD) patients in India. Reverse transcription PCR (RT-PCR) and cell-culture-based isolation of CV-A16 was done from the 55 clinical samples. The entire genome of the CV-A16 isolate was performed from the seven isolates. After the sequences were analysed, a phylogenetic tree was created using bioinformatics tools. The total genomic length obtained was 7411 base pairs (bp). Nucleotide similarity across various regions, including 5'UTR, P1, P2 and 3'UTR, ranged from 87.0-97.9 %, 77.0-95.4 %, 80.3-96.9 %, and 77.9-96.2 %, respectively. Correspondingly, similarities in the VP1 region's nucleotide and amino acid sequences were 91.4-96.4 % and 99.3-99.7 %, respectively. Phylogenetic analysis highlighted that CV-A16 strains identified in Pune, Maharashtra, were grouped within the same cluster. The analysed CV-A16 isolates in this study aligned with subgenotype B1c. These findings have far-reaching implications for the surveillance, prevention and management of HFMD and CV-A16. Monitoring the dynamics of CV-A16 strains, informed by the genetic characteristics identified here, will significantly impact strategies aimed at tackling HFMD and its associated public health challenges.

Project description:Introduction: Hand, foot, and mouth disease (HFMD) is a mild self-limited childhood infectious disease caused by a variety of enteroviruses (EVs). Aim: To investigate the molecular epidemiology of EVs associated with HFMD and their clinical presentation during the HFMD outbreak that occurred in the Jenin district, Palestine, from May to August 2024. Materials and Methods: Forty-four (44) throat and vesicular swabs were tested for enteroviral infections using two RT-PCR assays targeting both the 5'NTR and the VP1-2A regions of the enteroviral genome for the diagnosis and genotyping. Patients' demographic data and clinical history were used to create an epidemiological curve. EpiInfo free software was used to draw a cluster mapping. MEGA-X was used to construct a maximum likelihood (ML) tree. PopArt 1.7 software was used to construct neighbor-joining network. Results: The mean age of the study sample was 2.08 (0.25-12 years) with 95% (42/44) under five years old. The male/female ratio was 0.9. All cases presented with typical HFMD signs and symptoms with variable sites of signs. Of the 44 samples, 36 yield positive RT-PCR targeting the 5'NTR. Seven randomly selected positive RT-PCR-5'NTR samples were sequenced using Sanger sequencing for genotyping. It was shown that all were CV-A16 sub-genogroup B1c. Phylogenetic analysis of VP1-2A region sequences showed that all Palestinian CV-A16 isolates form a pure haplogroup of CV-A16 sub-genotype B1c. Furthermore, although haplotype network analysis showed high variation between the viral sequences, the haplotype analysis supported the ML phylogenetic tree in having them all in one haplogroup. Conclusion: CV-A16, sub-genotype B1c was the virus responsible for the HFMD outbreak in the Jenin district of Palestine in the summer of 2024. Phylogenetic and haplotype analysis showed that CV-A16 strains cluster closely with each other and very close to an Indian isolate (OR437338.1), indicating the monomorphic nature of this strain with low genetic variation and the probability of virus importation.

Dataset Information

From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD).

Publications

From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD).

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