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FMD vaccines | Different types for the maximum protection

 




FMD vaccines | Different types for the maximum protection


FMD vaccine is one of the most veterinary aspects that must be considered to control this serious disease.


Foot and Mouth Disease (FMD) is a خ contagious disease affecting pigs, cattle, sheep, goats, buffalos, and other cloven-hoofed animals.


This disease has a serious economic impact in endemic countries, range from $6.5 to $21 billion annually.


So, prevention and vaccination against the disease are the keys.


Dr.provet decided to focus on the FMD vaccine in detail through this article.


This article will address:

  • Factors affecting the severity of FMD.
  • The predisposing factors of rapid re-emergence of FMD
  • Characters of the ideal FMD vaccines.
  • Traditional inactivated FMD vaccines.
  • Dose of inactivated FMD vaccines 
  • Disadvantages of traditional inactivated FMD vaccines.
  • Live attenuated vaccines.
  • Disadvantages of FMD attenuated vaccines.
  • DNA vaccines.
  • Advantages of DNA vaccines.
  • Disadvantages of DNA vaccine.
  • Peptide vaccines.
  • Live viral vector vaccine.
  • Virus-like particles (VLPs).
  • Marker vaccine development and DIVA capacity.
  • Aphthization.



The FMDV has 7 immunological serotypes (A, O, C, SATs 1-3, and Asia-1) that contain 60 topotypes, so presence of effective vaccines against the virus is a challenge.


It's necessary to maintain specific vaccines for each region according to the endemicity of the virus,

For example:

  • Africa has 4 endemic serotypes (SAT1-3, A, O, and C).

  • South America has 3 endemic serotypes(A, O, and C),

  • In Asia,  Asia 1, A, O, and C serotypes are endemic.


Factors affecting the severity of FMD


The severity of the disease differs according to:


  • Species susceptibility.

  • Genetic properties of the virus serotype.

  • Previous infection or vaccination.

  • Methods of inactivation of FMD virus



The predisposing factors of rapid re-emergence of FMD


Some factors contribute to the rapid re-emergence of FMD, including:


  • Multiple genetic serotypes and topotypes of the virus.

  • Broad species tropism.

  • High infectivity rate.

  • The activity and movement of both animals and humans.

  • Various modes of transmission.

  • Rapid replication rate.

  • Excretion of virus in large amounts.

  • Rapid environmental changes.

  • High growth in international trade.

  • Extraordinary transmissibility makes FMDV difficult to be controlled.





Characters of the ideal FMD vaccines 


The FMD vaccines should have specific properties to can perfectly control the disease by applying the perfect biosecurity steps.


These properties include:


  • Potent, safe, and non-pathogenic to the vaccinated animals.


  • Induce immune response in a single-shot vaccination especially in emergency vaccination.


  • Provide rapid onset of the immune response.


  • Give long-lasting, sterile immunity with no carrier states.


  • Require a low-cost budget.


  • Has DIVA capacity (allow easy differentiation between vaccinated and infected animals).


  • Neither need cold chain containment nor high biosecurity measures during manufacture.


  • Multivalent (protect against serotypes and sub serotypes).







Traditional inactivated FMD vaccines


They are monovalent, bivalent, or multivalent vaccines that protect the clinical signs of FMD, and they are closely related to the vaccine strain.


They can be aqueous-, oil-emulsion-,, or aluminum-based inactivated vaccines.


The concentration of this killed vaccine differs according to the antigen used, the purpose of its application, and the manufacturer.


For example, it can be concentrated to the equivalent of three times the 50% protective dose (PD50) giving moderate protection.


Also, it can be concentrated to 6 times PD50 giving a higher effect especially in emergency vaccination of the FMD free countries.


Methods of inactivation of FMD virus


The virus can be inactivated by using:

  • binary ethyleneimine.

  • pure ethyleneimine and other aziridines. 

  • Formaldehyde.

  • virion-associated endonuclease.

  • Nonchemical hydrostatic pressure (HP).



Dose of inactivated FMD vaccines 


The extremely concentrated vaccine protects animals within one week.


It's recommended to provide 2 primary injections with one-month intervals.


It should be followed by repeated injections every 4-6 months for animals up to two years old.


The additional boosters should be repeated yearly.




Disadvantages of traditional inactivated FMD vaccines


  • Expensive and need to be kept cold

 as FMDV is a heat-sensitive virus, so the vaccines can be lost due to little higher temperatures.


  • High-risk factor during manufacturing


Production of vaccine antigen requires huge quantities of the FMD virus to get 1000 - 5000 liter of culture fluid.


During this process, escaping of virus from manufacturing facilities before complete inactivation is a risk.


So it requires highly controlled laboratory biosafety.


  • little or no cross-protection against various strains


The vaccine must antigenically match the wild-type FMDV responsible for the outbreak and provide good cross-protection against different strains.


So, it needs to include several different serotypes, which may stress the animal’s immune system.



  • Difficult to differentiate between infected and vaccinated animals


The false-positive resulted animals are due to the presence of the residual protein of traditional inactivated FMD vaccines.


So.the differentiation between the infected animals and vaccinated animals is difficult.



  • little effect on the carrier animals


Using the traditional inactivated FMD vaccines cannot provide full protection against persistent infection as it can't prevent primary infection.


It can only protect from generalization, and so more than half of the vaccinated animals may become carriers.



As a result of these disadvantages, the researchers do their best to get alternative vaccines to overcome the limitations of the traditional inactivated FMD vaccines, including:


  • Peptide vaccines.

  • DNA vaccines.

  • Live vector vaccines.

  • Novel attenuated vaccines.

  • DIVA capability and marker vaccines are very necessary for the easy differentiation of infected animals from vaccinated animals.


All of them has no risk to the vaccinated animals except for:

  • DNA vaccine: it can be recombined with other genomes.

  • attenuated vaccines: it can be potentially reverted to the virulent state.





  • Live attenuated vaccines


It's FMD virus that is subject to attenuation through one of the following means:


  • passing through cultured cells (conventional means).


  • utilizing molecular virology techniques to deoptimize or delete some genes (novel means).


The new attenuated FMD vaccines are more stable and have a low risk of reverting to virulence.


Disadvantages of FMD attenuated vaccines


This vaccine still has some limitations such as:


  • It's not safe for all animal species as the virus may be attenuated for one animal species but remain virulent for others.


  • There's a narrow margin between loss of virulence and loss of immunogenicity.





  • DNA vaccines 


It's a type of FMD vaccine that is usually a plasmid containing the target sequence of a microbial gene under the control of a promoter for gene expression and induction of an immune response.


Advantages of DNA vaccines


The DNA vaccine has some good features, including:


  • It can simulate both T and B cells.


  • It's not stressful to the immune system of the vaccinated animal.


  • safe vaccine because of the lack of infectious agents.


  • Easy to be manufactured and produced.

  • stable and do not require a cold-chain facility.


  • include marker genes with DIVA capability.


Disadvantages of DNA vaccine 


  • It requires multiple doses with large amounts of DNA to support its action.


  • Antibodies induced by DNA vaccines can target the host DNA.


  • It's used to produce target protein antigens, but not lipopolysaccharide antigens.


  • Peptide vaccines 


This type of FMD vaccine consists of a single linear peptide corresponding to the FMDV capsid proteins or containing T-cell and/or B-cell epitopes. 


Most peptide vaccines depend on carrier proteins that support the potency and safety of the vaccines such as ovalbumin or bacterial toxoid, conjugated with the peptide.


Complex mixtures of peptides with several antigenic variants are more immunogenic than single peptides.


Advantages of FMD peptide vaccine


The peptide vaccine has many advantages, including:

  • low-cost production.

  • Safe and stable vaccine.

  • No need for using infectious FMDV during its manufacture.


  • Live viral vector vaccine


It's the type of FMD vaccine that is characterized by:

  • It can perfectly express foreign genes.

  • No integration in the host genome.

  • It has a limited host range.

  • Contain insertion site for foreign genes.

  • Safe and non-pathogenic for the vaccinated animals.

  • Cost-effective to produce.




using viral vectors to transport immunogenic viral structural proteins is the main principle of this type of FMD vaccine to stimulate cell-mediated and humoral immune response through their expression in vector-infected cells.


  • Virus-like particles (VLPs)


This type of FMD vaccine includes only FMDV capsid proteins and lacks an infectious genome.


Several expression systems, including eukaryotic and prokaryotic systems, have been used for delivering virus-like particles (VLPs). 


  • Marker vaccine development and DIVA capacity


Using this vaccine is very important to control outbreaks and screen vaccinated animals to identify carriers.


It helps in distinguishing the vaccinated animals from infected animals by purification of viral antigens that eliminates NPs.



  • Aphthization

It's a simple method used to stimulate the immune response in susceptible animals.


It can be carried out by rubbing a rough instrument in the mouth of a diseased animal than in the mouth of the susceptible animals.


Advantages of Aphthization 

This simple method leads to:

  • Mild disease with a short incubation period.

  •  High level of immunity against the local strains of the virus.

  • Reduce the veterinary effort to control the disease.


Finally, Improving FMD vaccines and applying the perfect biosecurity is the key to ideally control FMD in both endemic and free countries.



Written by: Dr. Mai Foda




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