Introduction As the man was eradicating diseases that had been threatening his existence, new and more dangerous diseases were emerging. This led to an increased headache for doctors and other research experts in the field of medicine who were using any available methods to control the new diseases. While in the past it was easy to control diseases using the traditional methods, the diseases which have emerged are more resistant to some of those methods because they have undergone gene mutations. As a result, scientists have been forced to come up with new methods through which these diseases can be controlled. Among the methods which have emerged to protect man and other living things from these dangerous diseases, DNA vaccination has emerged as one of the best since it attacks the genes which cause these diseases. In this review, we shall go through the various methods and strategies which scientists have been using in optimizing and making the DNA vaccines as efficient as possible. These different strategies include the co-expression of stimulatory molecules, the use of either localization or secretory signals among other methods. The three optimization methods scientists have been using to optimize DNA vaccines are the use of regulatory elements, optimization of the codons, and addition of the kozak sequences. The DNA vaccine DNA is the gene-carrying component that carries the genetic information required in the functioning of all living organisms. Its main long-term role is the storage of genetic information. The DNA is made of two strands which are anti-parallel and attached to each strand are nitrogenous bases which translate into a particular amino acid. Each nitrogenous base is attached to a sugar (Calladine 2004). The nitrogenous sugar bases are arranged into a specific sequence of a particular amino acid which then forms a particular gene. When making DNA vaccines, genetic engineers modify or interfere with gene sequence in order to come up with a specific kind of amino acid that can function as a vaccine. A DNA vaccine is therefore described as the changed or the modified DNA sequence (Roat-Marone 2007). The DNA sequence which is created, codes for a specific antigenic protein of the pathogen. As a result, when DNA vaccines are inserted into cells of human beings, they are translated to form antigenic proteins and since these antigenic proteins are not recognizable by the body, the body creates an immune system towards it. The DNA vaccine helps the body in achieving immunity in this way. DNA vaccines are derived from bacteria that possess plasmid vectors which are usually used as the transferring agents from the vector to the body (Barrett& Stanberry 2009). Regulatory elements A gene is usually divided into two regions. One is the transcription region while the other is the regulatory region. The transcription region is the region that is usually transcribed into an RNA molecule. The regulatory region on the other hand is divided into two regions: the cis-regulatory region and the other which is the trans-regulatory element, (Thakurta 2006). When making DNA vaccines, scientists usually use the trans-regulatory elements which are the DNA sequences that encode the transcription factors. Studies have shown that the strength of a promoter (where gene transcription i