NOVEL IMMUNIZATION STRATEGIES TO CONTAIN THE EVOLUTION AND SPREAD OF INFECTIOUS DISEASES GLOBALLY

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We are in the age of pandemics, infectious diseases with a global reach. The novel coronavirus disease 2019 (COVID-19) is one typical reminder of what infectious diseases can do to humans and the economy. Since the emergence of COVID-19, a lot have happened wrongly, especially in the disruption of economies and untold number of morbidity and mortality associated with COVID-19 around the globe. The infectiousness and global spread of COVID-19, coupled to the morbidity and mortality of the disease has made many pharmaceutical companies and governments of some developed nations to race to develop a vaccine to contain the unabated spread and morbidity/mortality associated with COVID-19. It is believed that if a vaccine is developed on time, the spread of COVID-19 as well as the morbidity and mortality associated with the viral disease can be sustainably contained. This is why it is important to elucidate the advantages and significance of some new immunization strategies.

Most immunization preparations are produced from whole microorganisms or toxoids/toxins produced from these microorganisms. However, there are several other methods for producing antigens suitable for immunization. Immunization (also known as vaccination) is defined as the inoculation of a host (human or animal) with inactive or weakened (i.e., attenuated) pathogens or pathogen products (such as toxins) to stimulate protective immunity in the recipients. Alternative immunization strategies using bioengineered molecules (such as synthetic peptides and others) eliminate the exposure of the vaccine-recipient hosts to microorganisms and, in some cases, even to protein antigen. Application of these strategies is providing safer vaccines targeted to individual pathogen antigens; and in the end, this new immunization approaches becomes more specific and targets the invading pathogen in the recipient.

These new immunization strategies include:

  1. Recombinant vector vaccine
  2. DNA vaccines  
  3. Recombinant-antigen vaccines (in which recombinant DNA proteins are used as immunogens)

Synthetic and Genetically Engineered Immunizing Agents: The simplest alternative approach to vaccine development is the use of synthetic peptides. To make a vaccine, a peptide can be synthesized that corresponds to a known antigen on an infectious agent or pathogen. For example, the structure of the protein antigen responsible for immunity to foot- and-mouth virus, an important animal pathogen, is known. A synthetic peptide of 20 amino acids constituting an important antigenic determinant of the protein has been made and attached to suitable carrier molecules. This synthetic vaccine evokes an excellent neutralizing antibody response to foot-and-mouth virus. However, as a general method, this approach has one major problem: The entire sequence, representing the complete antigenic profile of the protein, must be known to make an effective vaccine. The entire genomic sequences of a large number of pathogens are now known, however, providing the information necessary to identity the antigenic profile of each.

High-throughput molecular biology techniques can be used to make vaccines using information derived from genomics of pathogens. For example, genes that encode antigens from virtually any virus can be cloned into the vaccinia virus genome and expressed. Inoculation with the genetically engineered vaccinia virus can then be used to induce immunity to the product of the cloned gene. Such a preparation is known as a RECOMBINANT VECTOR VACCINE. [Immunity is defined as the ability of an organism (including humans and animals) to resist an infection, especially infections or diseases caused by infectious disease agents or pathogens]. This method, upon which a recombinant vector vaccine is produced, depends on the identification and cloning of the gene that encodes the antigen and also on the ability of the vaccinia virus to express the cloned gene as an antigenic protein.

An effective recombinant vaccinia-rabies vaccine has been developed for use in animals. Another new immunization strategy involves the use of recombinant DNA proteins as immunogens. [Immunogens are molecules that are capable of eliciting an immunological response in a human or animal host] In the use of recombinant DNA proteins as immunogens, first, a pathogen gene must be cloned in a suitable microbial host that expresses the protein encoded by the cloned gene. The pathogen protein can then harvested and used as a vaccine; such a vaccine is called a recombinant-antigen vaccine. For example, the current hepatitis B virus (HBV) vaccine is a major hepatitis surface protein antigen (HbsAg) expressed by yeast cells. A vaccine that is effective against human papillomavirus (HPV) – the causative agent of perineal warts or cervical cancer in females, is also recombinant vaccine made in yeast cells.

DNA VACCINES

A new method for immunization is based on the expression of cloned genes in host cells. Bacterial plasmids containing cloned DNA are injected intramuscularly into a host animal. After several weeks, the host responds with TC cells, TH1 cells, and antibodies directed to the protein encoded by the cloned DNA. Taken up by the host cells, the DNA is transcribed and translated to produce immunogenic proteins, triggering a conventional immune system response. These plasmids are called DNA vaccines. DNA vaccine strategies may provide considerable advantages over conventional immunizations. These advantages are as follows:

  1. Firstly, because only a single foreign pathogen gene is normally cloned and injected, there is no chance of an infection as there might be with attenuated vaccine.
  2. Secondly, genes for individual antigens such as a tumour-specific antigen, or even a single antigenic determinant, can be cloned, targeting the immune response to a particular cell component.
  3. The response can also be targeted directly to antigen presenting cells (APCs) by including a major histocompatibility complex (MHC) class II promoter in the gene construct.

The promoter assures selective expression in dendritic cells, B cells, and macrophages, the only cells capable of using the MHC II protein. The expressed and processed antigen can then be presented on both MHC I and MHC II proteins. Thus, a single bioengineered plasmid can encode an antigen and elicit a complete immune response, including immune T cells and antibodies. In at least one case, an experimental DNA vaccine consisting of an engineered MHC-peptide complex protected mice from infection with a cancer-producing papillomavirus.

Further reading

Madigan M.T., Martinko J.M., Dunlap P.V and Clark D.P (2009). Brock Biology of Microorganisms, 12th edition. Pearson Benjamin Cummings Inc, USA.

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