Using molecular approaches (recombinant DNA technology), it is possible to identify specific virulent genes of different pathogens.
The virulent gene can be deleted are modified by inducing multiple mutations through molecular technology. Using the pathogens with modified genes, it is possible to develop a safer vaccine than using conventional attenuation technologies.
For example, the degree of attenuation can be controlled by deleting or mutating the appropriate gene or groups of genes. By deleting an entire gene or portion of a gene, the chances of reversion to virulence is dramatically reduced.
The probability of reversion to virulence can further be reduced if two different genes separated by some space are deleted or mutated. Based on these factors, the newly engineered vaccines are much safer than the conventionally-produced live vaccines.
In addition to that these vaccines can also be used as “marker vaccines” (A marker vaccines is a vaccine that helps to differentiate infected and vaccinated subjects). By deleting an essential gene, one can develop replication of incompetent viruses which are extremely safe, as they cannot be transmitted in the environment.
A further advantage of live vaccines is that they can often be delivered via natural route of infection (mucosal route), thus inducing not only systemic immunity, but also mucosal immunity. By developing mucosal immunity, one can prevent the initiation of infection as well as preventing disease.
For example potential live vaccines using recombinant vaccinia viruses have been constructed for both hepatitis B and herpes simplex. These recombinant vaccinia viruses express cloned genes of the hepatitis B virus surface antigen (HBsAg) or the glycoprotein D from herpes simplex virus (HSV-gD).
Inoculation of rabbits with the recombinant vaccinia virus that expresses the HBsAg or HSV- gD elicits the production of high-titered antibodies. Immunization of mice with the vaccinia recombinant expressing HSV-gD gave complete protection on subsequent challenge with lethal doses of live herpes simplex virus.
Hybrid virus vaccines are stable and stimulate both cellular and humoral immunity. They are relatively cheap and simple to produce. Being live vaccines, smaller quantities are enough for immunization.
Potential disadvantages of genetically engineered vaccines
The use of vaccinia also carries the risk of adverse reactions associated with the vaccine and the virus may spread to susceptible contacts. At present, efforts are being made to attenuate vaccinia virus further and the possibility of using other recombinant vectors is being explored, such as attenuated poliovirus and adenovirus.