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Vaccines by Recombinant DNA Technology
A biological preparation, which evokes an immune response when administered into the body, is termed as vaccines. This usually consists of parts of pathogen in its weakened state or its products. This triggers an immune response from the body to the particular disease without actually causing the disease.

Catering to the needs of large number of diseases, numerous vaccines for a variety of diseases has been developed and still continues to do so.

Recombinant vaccines:
Biotechnology sector has also played its part in developing vaccines against certain diseases. Such vaccine which makes use of recombinant DNA technology is known as recombinant vaccines. It is also known as subunit vaccines.

Recombinant vaccines can be broadly grouped into two kinds:

(i) Recombinant protein vaccines: This is based on production of recombinant DNA which is expressed to release the specific protein used in vaccine preparation

(ii) DNA vaccines: Here the gene encoding for immunogenic protein is isolated and used to produce recombinant DNA which acts as vaccine to be injected into the individual.

Steps involved:
Production of recombinant vaccines involves the following steps:

(i) First and foremost, it is important that the protein which is crucial to the growth and development of the causative organism be identified.

(ii) The corresponding gene is then isolated applying various techniques. Further to this, an extensive study of the gene explains the gene expression pattern involved in the production of corresponding protein.

(iii) This gene is then integrated into a suitable expression vector to produce a recombinant DNA.

(iv) This rDNA is used as vaccines or is introduce into another host organism to produce immunogenic proteins which acts as vaccines.

Recombinant protein vaccines:
A pathogen upon infection produces proteins, vital for its functions, which elicit an immune response from the infected body. The gene encoding such a protein is isolated from the causative organism and used to develop a recombinant DNA. This DNA is expressed in another host organism, like genetically engineered microbes; animal cells; plant cells; insect larvae etc, resulting in the release of the appropriate proteins which are then isolated and purified. These when injected into the body, causes immunogenic response to be active against the corresponding disease providing immunity against future attack of the pathogen.
Based on the proteins involved in evoking immune response recombinant protein vaccines are of two types:

Whole protein vaccines: The whole immunogenic protein is produced in another host organism which is isolated and purified to act as vaccines.

Polypeptide vaccines: It is known that in the immunogenic protein produced, the actual immunogenic property is limited to one or two polypeptides forming the protein. The other parts of the protein may be successful in evoking an immune response but do not actually cause the disease. For eg: in the case of cholera caused by Vibrio cholerae, consists of three polypeptide chains like A1, A2, and B. The A polypeptides are toxic while B is non-toxic. Thus while producing vaccines, the polypeptide B is produced by rDNA technology and used for vaccination.

DNA vaccines:
It refers to the recombinant vaccines in which the DNA is used as a vaccine. The gene responsible for the immunogenic protein is identified, isolated and cloned with corresponding expression vector. Upon introduction into the individuals to be immunized, it produces a recombinant DNA. This DNA when expressed triggers an immune response and the person becomes successfully vaccinated. The mode of delivery of DNA vaccines include: direct injection into muscle; use of vectors like adenovirus, retrovirus etc; invitro transfer of the gene into autologous cells and reimplantation of the same and particle gun delivery of the DNA.
In certain cases, the responsible gene is integrated into live vectors which are introduced into individuals as vaccines. This is known as live recombinant vaccines. Eg: vaccinia virus. Live vaccinia virus vaccine (VV vaccine) with genes corresponding to several diseases, when introduced into the body elicit an immune response but does not actually cause the diseases.


(i) Since it does not involve actual pathogen, recombinant vaccines is considered to be safe than the conventional vaccines.
(ii) It induces both humoral and cellular immune response resulting in effective vaccination.

Risks involved:
(i) High cost of production.
(ii) Have to be stored at low temperature since heat destabilizes protein. Hence storage and transportation is tedious.
(iii) Individuals with immunodeficiency may elicit poor immune response.

Oral vaccines: a novel approach
The latest hot spot in the field of vaccine research is the development of vaccine which can be taken orally. Immunogenic protein of certain pathogens is found to be active when administered orally. The gene corresponding to such proteins is isolated and a gene construct is produced. This is introduced and expressed in a plant genome which results in production of such immunogenic proteins in the parts of the plant where it is expressed. These when fed into animals or mainly humans, the person becomes vaccinated against certain pathogen. Such vaccines are also known as edible vaccines. An exciting invention is production of ‘melt in the mouth’ vaccines that can be administered by placing them under your tongue which delivers it into the blood stream. The most important example is the production of flu vaccine by Bacillus which melts in the mouth. The tremendous benefit of such vaccines is the comfort of administration, low cost and ease of storage.
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All recombinant vaccines fall into three fundamental classes namely, live genetically modified, recombinant inactivated, and genetic vaccines.

Live genetically modified vaccines can be bacteria or viruses, generally with two or more genes inactivated or deleted. They can also be vaccines carrying a foreign gene from a different disease agent, referred to as vaccine vectors. These vaccines are developed to attenuate the infectious agent. An additional recent technique of creating a live genetically modified vaccine is to utilize an infectious clone of the disease causing agent. An infectious clone is produced by isolating the complete genome of the disease agent in the lab. This isolated or cloned genome can be purposefully and specifically altered in the lab and then utilized to re-create the live genetically modified organism.

Recombinant inactivated vaccines are the subunit vaccines consisting of only a part of the entire organism. Subunit vaccines can be synthetic peptides produced in the lab. It can also be whole proteins extracted from the disease agent or the one that is expressed from the cloned genes. Numerous systems can be utilized to express a recombinant protein and the expression systems can be cell free or use entire cells. The expression systems that use entire cells includes prokaryotic such as Escherichia coli (bacteria based) and eukaryotic such as yeast, mammalian, avian or insect based systems. An additional type of recombinant subunit vaccines, referred to as virus-like particles or VLPs, can be generated when one or more cloned genes that characterize the structural proteins of a virus are expressed at the same time and self-assemble to form VLPs.

Genetic or DNA vaccines are generally plasmids, which contain a foreign gene from an infectious agent and a promoter to initiate its expression in the target animal. These plasmids can be maintained in bacteria such as E. coli .The plasmids are purified from the bacteria and the DNA is injected directly into the animal by intramuscular means or into the skin. The cells of the animal take up the naked DNA, and as a result the immune response is induced to the protein that is expressed from the foreign gene.
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