Introduction Course to Porcine Immunology

DEAD AND LIVE ATTENUATED VACCINES

Dead and/or live attenuated vaccines have been the basis of the control and eradication of a large majority of infectious diseases up until our days. 


From the work of Louis Pasteur until now, many different vaccines against viral and bacterial diseases have been developed using several techniques in order to attenuate the infectious agents and choose non-virulent colonies, or to produce the total inactivation so as to produce of dead vaccines. 

What is an attenuated vaccine?

Attenuated vaccines use one (or several) live infectious agents, which are homologous to the one producing the disease, but with its virulence attenuated. Thus the vaccine can induce a lasting immunity against the virulent homologous agent yet at the same time it does not produce any secondary lesion in the animal. 

Usually these kinds of vaccines are obtained from homologous strains which are naturally attenuated, or from virulent agents that are attenuated in a stable way following different techniques. 

The most frequently used attenuation technique consists of growing the agent in cell culture (viruses) or in media (bacteria) until it looses its virulence; the agent keeps its capability of replication but cannot produce the disease, yet at the same time it can induce immunity. 

ATTENUATED VACCINES

INACTIVATED VACCINES

Stimulation of CD 4+ and CD 8+ Mainly CD 4+
CYTOKINES (Interferon)  Less CYTOKINES
LESS ANTIGEN   MORE ANTIGEN
LESS STORAGE 
STABILITY 
MORE STORAGE
STABILITY
LESS SAFE SAFER 
ADJUVANTS NOT CRITICAL ADJUVANTS ARE CRITICAL

Cell in vitro culture

Most viruses are grown in stable cell cultures. These cells are usually adhered to the surface of the culture flask (although some of them are suspended in the culture medium), where they are later infected by the virus. This way, a large number of viral particles are produced. 

Virus culture in embryonated eggs 

Virus culture in embryonated eggs. Some viruses cannot be cultured in cell lines and replicate in bird eggs. 

 

What is an inactivated or dead vaccine?

MAIN VACCINES USED IN THE PORCINE SPECIES
Actinobacillus pleuropneumoniae
AUJESZKY´S DISEASE
GLÄSSER´S DISEASE
ENTEROTOXAEMIA
FOOT AND MOUTH DISEASE
PORCINE INFLUENZA
ERYSIPELAS
ATROPHIC RHINITIS
PARVOVIROSIS
CLASSICAL SWINE FEVER
PORCINE REPRODUCTIVE AND RESPIRATORY  SYNDROME (PRRS)
Mycoplasma hyopnemoniae
Pasteurella multocida
Serpulina

Dead or inactivated vaccines consist of complete but chemically or physically inactivated microorganisms. These vaccines when compared with attenuated vaccines which have, as their main advantages:  stability and safety as well as their easy conservation. However, they usually induce a smaller immune response, mainly related to CD 4+ lymphocytes and antibody production. 

The most widely used methods of inactivation are based on chemical or physical mechanisms that do not alter the immune response. Some of them are: formaldehyde and chelating agents (ethylene oxide, propiolactone, ethylenoimina, etc.). These substances produce cross linking in the nucleic acid chains, which inactivates the microorganism but not its proteins. Dead or inactivated vaccines are also produced from inactivated bacterial exotoxins, that, as in the case of tetanus, give very good results.

Microcarrier

Partial view of an industrial centrifugation unit for bacteria. This is used for the production of bacterial vaccines.  

Producción de vacunas bacterianas.

The surface for the bacteria culture can be increased using microcarriers. These are particles that allow the adherence and growth of million of cells. Thus, culture surface is  increased "n" times. 

 

What are adjuvants?

Scientists discovered at the beginning of the last century, that different salts bound to antigenic material induced an enhanced production of antibodies and the enhancement of the immunological memory of the animals that received those vaccines. These substances, known as adjuvants, act by improving antigen presentation, sequestering vaccine antigens and later liberating them in a slow and prolonged way. At the same time, they induce a slight inflammation favoring chemoattraction of  antigen presenting cells.

The most widely used adjuvants are aluminum salts (aluminum hydroxide or aluminum phosphate). When inoculated they produce a small granulome that allows the delayed liberation of the antigen (long lasting antigenic stimulation) and the attraction of antigen-presenting cells. This increases the immune response. Aluminum hydroxide is still used in the porcine species, especially with highly immunogenic antigens (for example: parvovirus vaccine). Other adjuvants (incomplete Freund adjuvant) are a mixture of the antigen and water and mineral oils; the complete adjuvant also has dead Mycobacterium tuberculosis. The effect of these adjuvants is similar, i.e; they induce inflammation and the attraction of the presenting cells. They are also used in the porcine species, especially with antigens with a low immunogenic capability (for example: foot and mouth disease virus  and porcine influenza) 

More recently other types of adjuvants are being used, as Carbomer and saponines, (Quil A). This last one is not frequently used, because of its destructive character. Those substances known as immune stimulating complexes or ISCOMs have good enhancing characteristics, without presenting secondary effects, but their commercial use is limited. Lastly, the association of vaccine antigens, adjuvants and  some cytokines (as IL 2 or interferon) are gradually being studied more and will probably be used  more often in the future.  

MAIN ADJUVANTS USED IN PORCINE VACCINES
ALUMINUN HYDROXIDE
MINERAL OILS

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