Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

Q: What is the clinical evidence from this study?

Study design: Review. Population: Hand, foot, and mouth disease (HFMD). Intervention: Antigenic peptide-based vaccines and neutralizing monoclonal antibodies vs. Inactivated monovalent EV-A71 vaccines.

Mohd Ishtiaq Anasir; Chit Laa Poh

doi:10.3390/ijms20061256

March 13, 2019International Journal of Molecular SciencesOpen Access

Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

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Key result

Peptide and virus-like particle vaccines show promising multivalent enterovirus protection.

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Why the study?

Inactivated EV-A71 vaccines do not protect against CV-A16 and other HFMD etiological agents, necessitating exploration of antigenic peptide-based vaccines and neutralizing monoclonal antibodies.

Do antigenic peptide-based vaccines and neutralizing monoclonal antibodies provide broader multivalent protection against HFMD causative viruses compared to monovalent inactivated EV-A71 vaccines?

Key Points

To review available evidence on antigenic peptides and neutralizing antibodies across enteroviruses causing hand, foot, and mouth disease, and to outline strategies for designing multivalent vaccines and therapeutic antibodies.
Narrative review synthesizing structural biology, epitope mapping, and preclinical and clinical vaccine developments across Enterovirus A serotypes (EV-A71, CV-A16, CV-A6, and CV-A10).
Analysis of licensed monovalent inactivated vaccines, epitope candidates within structural viral proteins, and emerging multivalent platforms including virus-like particles and synthetic peptides.
Licensed monovalent inactivated EV-A71 vaccines show high serotype-specific efficacy (Sinovac at 94.8%, CAMS at 97.4%, and Vigoo at 90.0%), but fail to elicit sufficient cross-neutralizing antibodies against CV-A16, CV-A6, or CV-A10.
Key linear neutralizing epitopes mapped to the external capsid protein VP1, including synthetic peptides SP55 (amino acids 163–177) and SP70 (amino acids 208–222), with SP70 eliciting high titers of neutralizing IgG1 antibodies against EV-A71.

Structured PICO

Do antigenic peptide-based vaccines and neutralizing monoclonal antibodies provide broader multivalent protection against HFMD causative viruses compared to monovalent inactivated EV-A71 vaccines?

P

Population

Preclinical animal models (primarily neonatal and adult mice, rabbits) and in vitro cell lines (rhabdomyosarcoma and Vero cells) used to study Enterovirus A species (EV-A71, CV-A16, CV-A6, CV-A10) causing hand, foot, and mouth disease (HFMD)

I

Intervention

Antigenic peptide-based vaccines (including synthetic peptides SP55, SP70, PEP71, VP4N20, tandem multi-linear neutralizing epitopes [mTLNE], and chimeric virus-like particles [EV-A71 VLP, HBcAg-VLP]) and neutralizing monoclonal antibodies

C

Comparator

Licensed formaldehyde-inactivated monovalent EV-A71 vaccines

O

Outcome

Induction of cross-neutralizing antibodies and passive/active protection against lethal viral challenges of EV-A71, CV-A16, CV-A6, and CV-A10surrogate

This review highlights structural epitopes and virus-like particle platforms to guide the rational design of multivalent peptide-based vaccines and humanized monoclonal antibodies against the multiple enteroviruses causing hand, foot, and mouth disease.

Limitations

Linear peptides used in isolation are often weakly immunogenic.
Licensed inactivated EV-A71 vaccines fail to elicit cross-neutralizing antibodies against other HFMD causative agents such as CV-A16, CV-A6, and CV-A10.
Most neutralizing monoclonal antibodies identified so far are derived from mice and require humanization prior to clinical use to avoid immune rejection.
Linear peptides used in isolation are often weakly immunogenic
Large-scale production of multiple single VLPs for a tetravalent vaccine is costly and time-inefficient
Chemical treatments (e.g., formalin) can alter native surface-exposed epitopes of CV-A16
Most identified neutralizing monoclonal antibodies are murine-derived and require humanization before clinical application in humans

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Implication

May guide multivalent HFMD vaccine design; leaves open clinical validation of peptide/VLP platforms.

Abstract

Hand, foot, and mouth disease (HFMD) commonly produces herpangina, but fatal neurological complications have been observed in children. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) are the predominant viruses causing HFMD worldwide. With rising concern about HFMD outbreaks, there is a need for an effective vaccine against EV-A71 and CV-A16. Although an inactivated vaccine has been developed against EV-A71 in China, the inability of the inactivated vaccine to confer protection against CV-A16 infection and other HFMD etiological agents, such as CV-A6 and CV-A10, necessitates the exploration of other vaccine platforms. Thus, the antigenic peptide-based vaccines are promising platforms to develop safe and efficacious multivalent vaccines, while the monoclonal antibodies are viable therapeutic and prophylactic agents against HFMD etiological agents. This article reviews the available information related to the antigenic peptides of the etiological agents of HFMD and their neutralizing antibodies that can provide a basis for the design of future therapies against HFMD etiological agents.

Discussion

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Cite This Study

Anasir et al. (2019) conducted a review in Hand, foot, and mouth disease (HFMD). Antigenic peptide-based vaccines and neutralizing monoclonal antibodies vs. Inactivated monovalent EV-A71 vaccines was evaluated. Antigenic peptide-based vaccines and virus-like particle platforms displaying linear epitopes like SP70 and PEP71 offer promising multivalent protection against EV-A71, CV-A16, CV-A6, and CV-A10.

synapsesocial.com/papers/6a78a685e29fd788c9f81b48 https://doi.org/10.3390/ijms20061256

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Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

Figures

Key Points

Structured PICO

Limitations

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Implication

Abstract

Discussion

Cite This Study

Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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