Novel Approaches to Foot-and-Mouth Disease Vaccine Development

Abstract Objectives: Stability is vital for potency of food-and-mouth disease virus vaccine preparation. However, the assembly of inactivated foot-and-mouth disease virus is poor stable and prone to dissociate into 12s under mild acidic or heating conditions, especially emulsified with oil-adjuvant. Thus, it is crucial to explore a suitable medium and condition to improve the stability and efficiency of inactivated FMDV vaccine. Results: In this study, the basic solution buffer and a serious of potential stabilizers, such as carbohydrate, amino acid, antioxidant, salt and antioxidant were screened for evaluating stable effect on FMDV antigen with aid of high performance size exclusion chromatography (HPSEC). On this basis, orthogonal experiment was performed to optimize and finally confirm the formulation. Anti-aging test were carried out to asses the efficiency of formulation on vaccine stability and the results showed that the vaccine was more stabler either stored at 37℃or 4℃. Moreover, physicochemical monitoring revealed that formulation had no influence on the properties of vaccine. The combined results suggested that the novel solution buffer would lower degradation and prolong shelf life of vaccine. In a word, the novel buffer is beneficial to make FMD vaccine more stable and effective, reducing the dependence on cold delivery and storage. This study also provides insight into the processes of optimization and inactivated vaccine development.

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A Proposal for the Classification and Nomenclature of Hand, Foot and Mouth Disease-Related Enteroviruses

10.21203/rs.3.rs-34737/v1 ◽

2020 ◽

Author(s):

Yajuan Dong ◽

Zhenzhou Wan ◽

Shenwei Li ◽

Jian-Hua Wang ◽

Xia Jin ◽

...

Keyword(s):

Vaccine Development ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Epidemiological Surveillance ◽

Subtype B ◽

Current Classification ◽

Foot And Mouth ◽

The Mean ◽

Phylogenic Relationship

Abstract Background: Enterovirus has diverged into many types, some of which cause hand, foot and mouth disease (HFMD) in children. The predominant enterovirus types associated with HFMD are EVA71, CVA16, CVA6 and CVA10. Subtyping of these enteroviruses is crucial to HFMD surveillance. Because of lacking proper and uniform criteria and being based on partial VP1 sequences, however, current classification resulted in some confusing and conflicting results. Method: We reclassified EVA71, CVA16, CVA6 and CVA10 using a combined criteria of phylogenic relationship and genetic distance. Results: Using the combined criteria, we classified EVA71 into seven genotypes of A–G, CVA16 and CVA6 into three subtypes of A-C, and CVA10 into nine subtypes/sub-subtypes of A-G, H1 and H2, and identified eight unclassified subtypes that lack genomic sequences. The mean genetic divergence was 15.5-33.8% between subtypes, 12-15% between sub-subtypes, and less than 12% within subtypes/sub-subtypes. In addition, we identified two new EVA71 inter-subtype recombinants RF01_CG and RF02_CG and demonstrated that EVA71 subtypes D and F and CVA10 subtype B experienced inter-subtype recombination events during early evolution. Conclusions: The new nomenclature proposal provides a reasonable framework for proper classification of enteroviruses, which will be useful for epidemiological surveillance of HFMD, disease management, and vaccine development.

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Human enterovirus 71 and hand, foot and mouth disease

Epidemiology and Infection ◽

10.1017/s0950268809991555 ◽

2010 ◽

Vol 138 (8) ◽

pp. 1071-1089 ◽

Cited By ~ 178

Author(s):

S. S. Y. WONG ◽

C. C. Y. YIP ◽

S. K. P. LAU ◽

K. Y. YUEN

Keyword(s):

Vaccine Development ◽

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Asia Pacific ◽

Human Enterovirus ◽

Human Enterovirus 71 ◽

Asian Pacific Region ◽

Route Of Transmission ◽

Foot And Mouth

SUMMARYHand, foot and mouth disease (HFMD) is generally a benign febrile exanthematous childhood disease caused by human enteroviruses. The route of transmission is postulated to be faeco-oral in developing areas but attributed more to respiratory droplet in developed areas. Transmission is facilitated by the prolonged environmental survival of these viruses and their greater resistance to biocides. Serious outbreaks with neurological and cardiopulmonary complications caused by human enterovirus 71 (HEV-71) seem to be commoner in the Asian Pacific region than elsewhere in the world. This geographical predilection is unexplained but could be related to the frequency of intra- and inter-typic genetic recombinations of the virus, the host populations' genetic predisposition, environmental hygiene, and standard of healthcare. Vaccine development could be hampered by the general mildness of the illness and rapid genetic evolution of the virus. Antivirals are not readily available; the role of intravenous immunoglobulin in the treatment of serious complications should be investigated. Monitoring of this disease and its epidemiology in the densely populated Asia Pacific epicentre is important for the detection of emerging epidemics due to enteroviruses.

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Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

PLoS ONE ◽

10.1371/journal.pone.0055228 ◽

2013 ◽

Vol 8 (1) ◽

pp. e55228 ◽

Cited By ~ 19

Author(s):

Haixue Zheng ◽

Jianhong Guo ◽

Ye Jin ◽

Fan Yang ◽

Jijun He ◽

...

Keyword(s):

Vaccine Development ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Foot And Mouth ◽

Growth Properties

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Epidemic dynamics, interactions and predictability of enteroviruses associated with hand, foot and mouth disease in Japan

Journal of The Royal Society Interface ◽

10.1098/rsif.2018.0507 ◽

2018 ◽

Vol 15 (146) ◽

pp. 20180507 ◽

Cited By ~ 14

Author(s):

Saki Takahashi ◽

C. Jessica E. Metcalf ◽

Yuzo Arima ◽

Tsuguto Fujimoto ◽

Hiroyuki Shimizu ◽

...

Keyword(s):

Time Series ◽

Time Series Data ◽

Vaccine Development ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Asia Pacific ◽

Series Data ◽

Inhibitory Interaction ◽

Epidemic Dynamics ◽

Foot And Mouth

Outbreaks of hand, foot and mouth disease have been documented in Japan since 1963. This disease is primarily caused by the two closely related serotypes of Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16). Here, we analyse Japanese virologic and syndromic surveillance time-series data from 1982 to 2015. As in some other countries in the Asia Pacific region, EV-A71 in Japan has a 3 year cyclical component, whereas CV-A16 is predominantly annual. We observe empirical signatures of an inhibitory interaction between the serotypes; virologic lines of evidence suggest they may indeed interact immunologically. We fit the time series to mechanistic epidemiological models: as a first-order effect, we find the data consistent with single-serotype susceptible–infected–recovered dynamics. We then extend the modelling to incorporate an inhibitory interaction between serotypes. Our results suggest the existence of a transient cross-protection and possible asymmetry in its strength such that CV-A16 serves as a stronger forcing on EV-A71. Allowing for asymmetry yields accurate out-of-sample predictions and the directionality of this effect is consistent with the virologic literature. Confirmation of these hypothesized interactions would have important implications for understanding enterovirus epidemiology and informing vaccine development. Our results highlight the general implication that even subtle interactions could have qualitative impacts on epidemic dynamics and predictability.

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Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity

Journal of Virology ◽

10.1128/jvi.01102-15 ◽

2015 ◽

Vol 89 (20) ◽

pp. 10500-10511 ◽

Cited By ~ 35

Author(s):

Jingshan Ren ◽

Xiangxi Wang ◽

Ling Zhu ◽

Zhongyu Hu ◽

Qiang Gao ◽

...

Keyword(s):

High Resolution ◽

Insect Cells ◽

Vaccine Development ◽

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Vaccine Antigen ◽

Coxsackievirus A16 ◽

Structure Based Drug Design ◽

Foot And Mouth

ABSTRACTEnterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) that affect more than a million children in China each year and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, the development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess nonnative antigenicity, are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. Here, we remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant viruslike particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilize the native antigenic state that is different from the one used in a natural virus infection. As expected, the mature CVA16 virus is similar to EV71; however, structural and immunogenic comparisons highlight differences that may have implications for vaccine production.IMPORTANCEHand-foot-and-mouth disease is a serious public health threat to children in Asian-Pacific countries, resulting in millions of cases. EV71 and CVA16 are the two dominant causative agents of the disease that, while usually mild, can cause severe neurological complications, leading to hundreds of deaths. EV71 vaccines do not provide protection against CVA16. A CVA16 vaccine or bivalent EV71/CVA16 vaccine is therefore urgently needed. We report atomic structures for the mature CVA16 virus, a natural empty particle, and a recombinant CVA16 virus-like particle that does not contain the viral genome. All three particles have similar structures and identical antigenicity. The recombinant particles, produced in insect cells (a system suitable for making vaccine antigen), are stabilized by recruiting from the insect cells a small molecule that is different from that used by the virus in a normal infection. We present structural and immunogenic comparisons with EV71 to facilitate structure-based drug design and vaccine development.

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Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s1678-9946201860070 ◽

2018 ◽

Vol 60 (0) ◽

Cited By ~ 6

Author(s):

Yu-Kang Chang ◽

Kou-Huang Chen ◽

Kow-Tong Chen

Keyword(s):

Molecular Epidemiology ◽

Vaccine Development ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Enterovirus A71 ◽

Current Vaccine ◽

Foot And Mouth

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Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide

Journal of Virology ◽

10.1128/jvi.00401-08 ◽

2008 ◽

Vol 82 (14) ◽

pp. 7223-7230 ◽

Cited By ~ 71

Author(s):

Carolina Cubillos ◽

Beatriz G. de la Torre ◽

Annamaria Jakab ◽

Giorgia Clementi ◽

Eva Borrás ◽

...

Keyword(s):

Disease Virus ◽

Vaccine Development ◽

Immunoglobulin A ◽

Cell Epitope ◽

Clinical Signs ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Potential Marker ◽

Mouth Disease Virus ◽

Foot And Mouth

ABSTRACT The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptide-immunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

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