Introduction:
In 1969, Enterovirus-A71 was first identified in the United States, which causes hand, foot, and mouth disease in infants and children worldwide.
The Enteroviruses are universally present and are transmitted from one person to another through direct contact. These viruses reside in the upper respiratory or gastrointestinal tract.
Prototypes of Enterovirus:
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Poliovirus: It causes mild illness, aseptic meningitis, or paralytic poliomyelitis.
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Non-polio Viruses: They can cause a wide variety of diseases in all age groups but occur mostly in children.
A high prevalence of this virus is seen in developing countries from the consumption of contaminated drinking water. The detection of Enterovirus-A71 can be done with the help of specimens from the nose, throat, feces, or cerebrospinal fluid (rarely) of the individual. However, to determine the type of Enterovirus, specific testing needs to be done. This specialized test involves molecular sequencing on genetic material from the nose, throat, or feces of the infected person.
What Is Enterovirus-A71?
Enterovirus-A71 is a neurological disease that can lead to severe complications and can often be fatal. In order to control this virus, vaccination is the most effective solution.
Currently, the three inactivated whole Enterovirus-A71 are being used. This vaccine is licensed by China National Medical Products Administration (CNMPA). Other vaccines under development include:
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Virus-like particles.
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Recombinant virus protein 1 (capsid protein).
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Live attenuated vaccines.
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Synthetic peptide vaccines.
Enterovirus-71 is commonly seen in young children and can lead to
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Neurological complications.
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Myocarditis (inflammation of the heart muscle).
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Hemorrhage.
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Death in severe cases.
Hence, to avoid these complications and overcome this deadly virus, widely acceptable protective vaccines and antivirals should be developed.
What Are the Symptoms of Enterovirus-A71?
Enterovirus-71 causes a mild illness that subsides on its own, such as hand, foot, and mouth disease, or it may show no symptoms at all. However, it can sometimes lead to severe neurologic disorders, such as meningitis, encephalitis (swelling of the brain and spinal cord), or acute flaccid myelitis (AFM).
What Is a Novel Vaccine Against Enterovirus-A71?
Enterovirus-71 belongs to the Enterovirus genus and Picornaviridae family.
Enterovirus -71 can be divided into three genotypes:
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Genotype A.
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Genotype B: Subgenotype B1 to B5.
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Genotype C: Subgenotype C1 to C5.
C4 is further divided into C4 a and C4 b.
In the Asia-Pacific region, subgenotypes B3, B4, C1, and C2 were circulated during the period of 1999 and 2016. C1 and C2 are spreading in Europe. In China, the most common genotype circulating is C4, while B4 and B5 are standard in other regions.
No U.S. FDA (food and drug administration) approved vaccine, or antiviral agent is available in the market right now that can fight against Enterovirus-A71.
However, the China National Medical Products Administration (NMPA) has approved three inactivated, whole-virus vaccines that are commercially available.
This vaccine has undergone clinical trials on a large scale and has proved to be effective against the Enterovirus-A71 associated with hand, foot, and mouth disease showing efficacy of up to 90 %. The vaccine was effective 100 % in patients below the age of five years for severe cases and 80 % for mild cases. Vaccination is the best measure that can be taken against the Enterovirus-71.
Whole Enterovirus-A71 Vaccine:
1.Inactivated Whole Enterovirus Vaccine-A71: The whole virus is inactivated. It is the safest and most convenient way to produce viral vaccines. This vaccine was licensed in China in 2015, but the U.S. FDA did not approve it. It is known as the three inactivated Enterovirus-A71 vaccine because it was developed by three different institutions, namely:
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Sinovac Biotech.
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Beijing Vigoo.
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Chineses Academy of Medical Science.
Proper screening and evaluation were carried out for vaccine production, and those strains were selected that induced cross-protecting antibodies. The efficacy of inactivated Enterovirus-A71 vaccines has been confirmed. The efficacy of the vaccine was 90 % against Enterovirus associated with hand, face, and mouth disease and 100 % against Enterovirus-A71 associated with hand, face, and mouth disease with neurological problems.
2. Live Attenuated Vaccines: The pathogenic molecular mechanism and the virulence determinants of the Enterovirus-A71 have not been completely understood. However, some virulence determinants have been identified, which have helped in the development of live attenuated vaccines. These vaccines are cost-effective and provide long-lasting immunity.
3. Virus-like Particle-Based Vaccines: The virus-like particle can show positive results in the future as it resembles the original virus in appearance and antigenicity. The virus-like protein shows innate and adaptive immunity. They do not contain the viral genome and cannot replicate in the host, making it a safer option.
Certain virus-like particle-based vaccines have been licensed, such as:
- Cervarix and Gardasil-9 for Human Papillomavirus.
- Recombivax HB and Engerix-B for Hepatitis B virus.
4. Recombinant Viral Protein1 Vaccines: Neutralization epitopes (antigenic determinants) are present in Enterovirus-A71 capsid protein. Various expression strategies, such as Escherichia coli (E. coli), Baculovirus, and HIV gag-based virus-like protein carriers, were used to express recombinant viral protein 1. The purified recombinant viral protein 1 protected mice from Enterovirus-71 infection; however, the protection was lower than that of inactivated Enterovirus vaccine.
Han et al. showed the modified Enterovirus-71 polyprotein P1 in Pichia pastoris as a potential vaccine candidate. P1 protein-induced continuous, high cross-neutralization antibodies for different Enterovirus-A71 subtypes in rabbits. Vaccination of pregnant mice cross-protected neonatal mice against different subtypes of Enterovirus-A71. With high immunogenicity and cross-protection against different Enterovirus-A71 subtypes, the P. pastoris expressed P1 protein makes a future Enterovirus-71 vaccine candidate.
5.Synthetic Peptide Vaccines: Synthetic peptides are safe and can be developed with high efficacy. This can be achieved by focussing on mapping the epitopes in Enterovirus-A71 capsid proteins. Various groups used a fusion protein strategy to express Enterovirus-A71 epitopes. The fusion protein produced an immune response and protected suckling mice from a heavy dose of Enterovirus-A71 infection.
Conclusion:
Enterovirus-A71 is the causative agent of hand, face, and mouth disease and can further cause other neurological complications and even death in children worldwide. The most effective way to combat this disease is through immunization. Persistent efforts are being made worldwide to produce novel vaccines to overcome this disease. Recent studies show a promising future in the development of a successful vaccine against Enterovirus-A71, which can be used worldwide.
