What is the clinical evidence from this study?

Study design: Other. Population: Hand-foot-and-mouth disease (HFMD). Intervention: ChiEV-A71 VLPs vs. PBS. Primary outcome: Survival against lethal EV-A71 and CVA16 challenge (p=<0.05).

January 19, 2015Open Access

Novel recombinant chimeric virus-like particle is immunogenic and protective against both enterovirus 71 and coxsackievirus A16 in mice

Q: What are the key findings of this study?

Passive immunization with anti-ChiEV-A71 VLPs sera conferred 100% protection against lethal challenge of both EV-A71 and CVA16 infection in neonatal mice.

HZHui ZhaoShanxi Agricultural University HLHaoyang LiNanyang Technological University JHJianfeng HanLanzhou University of Technology

Key Result

Passive immunization with anti-ChiEV-A71 VLPs sera conferred 100% protection against lethal challenge of both EV-A71 and CVA16 infection in neonatal mice.

Structured PICO

Does immunization with ChiEV-A71 VLPs elicit protective immunity against EV-A71 and CVA16 in mice?

Population

BALB/c mice used to evaluate the immunogenicity and protective efficacy of a chimeric VLP vaccine against EV-A71 and CVA16.

Intervention

Immunization with ChiEV-A71 VLPs (chimeric EV-A71 virus-like particles)

Comparator

EV-A71 VLPs or PBS (control)

Outcome

Humoral and cellular immune responses (IgG titers, neutralizing antibodies, cytokines) and survival after lethal challenge with EV-A71 or CVA16

A novel chimeric virus-like particle vaccine (ChiEV-A71) elicited robust immune responses and provided full protection against both EV-A71 and CVA16 in mice, offering a potential bivalent HFMD vaccine platform.

Main Result

Absolute Event Rate: 100% vs 0%

p-value: p=<0.05

Limitations

The geometric mean of neutralizing antibody titers induced by ChiEV-A71 was only 1:16 against CVA16, indicating limited efficacy of a single epitope.
Epitopes responsible for eliciting neutralizing antibodies that can protect humans against CVA16 infection need to be further identified.
Potential for antibody-dependent enhancement (ADE) from cross-reactive non-neutralizing antibodies needs investigation.

Abstract

Hand-foot-and-mouth disease (HFMD) has been recognized as an important global public health issue, which is predominantly caused by enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16). There is no available vaccine against HFMD. An ideal HFMD vaccine should be bivalent against both EV-A71 and CVA16. Here, a novel strategy to produce bivalent HFMD vaccine based on chimeric EV-A71 virus-like particles (ChiEV-A71 VLPs) was proposed and illustrated. The neutralizing epitope SP70 within the capsid protein VP1 of EV-A71 was replaced with that of CVA16 in ChiEV-A71 VLPs. Structural modeling revealed that the replaced CVA16-SP70 epitope is well exposed on the surface of ChiEV-A71 VLPs. These VLPs produced in Saccharomyces cerevisiae exhibited similarity in both protein composition and morphology as naive EV-A71 VLPs. Immunization with ChiEV-A71 VLPs in mice elicited robust Th1/Th2 dependent immune responses against EV-A71 and CVA16. Furthermore, passive immunization with anti-ChiEV-A71 VLPs sera conferred full protection against lethal challenge of both EV-A71 and CVA16 infection in neonatal mice. These results suggested that this chimeric vaccine, ChiEV-A71 might have the potential to be further developed as a bivalent HFMD vaccine in the near future. Such chimeric enterovirus VLPs provide an alternative platform for bivalent HFMD vaccine development.

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