Live attenuated viruses come with some disadvantages, but a growing number of alternatives exist.
Throughout the history of vaccine development, from the 1800s until today, the vast majority of vaccines have used inactivated or attenuated forms of viruses to trigger immune responses in the body. Effective as these traditional vaccines often are, they come with certain risks, especially for people with poorly functioning immune systems. Thus, the vaccine sector has increasingly focused on innovative technologies in recent years.
Here is a brief comparison of the advantages and disadvantages of traditional vaccine forms, against newer techniques for generated immunity to viral infections.
Live attenuated vaccines
The primary purpose of any vaccine is to train the immune system to respond to a particular infection. Live attenuated forms of viruses are the closest safe alternative to an actual viral invasion, and thus provide highly effective “practice runs” for the body’s immune responses, by triggering strong responses from cells and antibodies, often conferring lifetime immunity as a result.
Even so, attenuated viruses are not without risks. Like all living things, attenuated viruses have the potential to mutate unexpectedly into truly virulent forms. Although this type of mutation is extremely rare, and can often be prevented by preparations in the laboratory, it remains within the realm of possibility.
In addition, even attenuated forms of viruses can pose serious risks to people with damaged or weakened immune systems, such as those infected with HIV. Plus, live attenuated viruses need to be refrigerated in order to remain effective. This makes them impractical for areas with limited refrigeration infrastructure, such as developing countries.
Although live attenuated vaccines for many viruses are relatively easy to create in the lab, a growing array of alternatives now exist on the market.
Unlike live attenuated vaccines, which are created by “disarming” the virus in question, inactivated vaccines are produced by actually killing the infectious organism, which can still trigger immune responses even while no longer alive. This approach circumvents many of the most common issues with live attenuated viruses, including the risk of harmful mutation and the need for refrigeration.
However, inactivated viruses typically stimulate a weaker response from the immune system than live attenuated viruses do. This means multiple doses are often required in order to confer lifelong immunity, and additional booster shots may be needed at intervals throughout the remainder of a patient’s life.
The low cost of producing inactivated viruses, and the ease of distributing them to clinics around the world, make them attractive candidates for clinical stage development.
Certain viruses are simply too risky to distribute, even in attenuated or inactivated forms. In these cases, virus-like particles (VLPs) provide a safe alternative. VLP vaccines contain assemblages of proteins that closely imitate the surface structures (epitopes) of specific viruses. These particles trigger similar immune responses to those elicited by the virus, preparing the immune system to recognize and respond to the invader if it is ever encountered.
In fact, in certain cases, VLPs may actually provide stronger and longer-lasting protection against viruses than traditional vaccines can confer. Research has revealed that this is likely to be the case for influenza (flu) vaccines, and may be true of other viruses as well. VLP production can also take place in a fraction of the time needed to generate viruses for conventional vaccines, offering a distinct advantage in cases where containment time is of the essence.
For all these reasons, VLPs are gaining popularity as targets for clinical-stage drug development; and many more are expected to appear on the market within the coming years.
One of the most cutting-edge frontiers in vaccine research is that of nucleic acid vaccines, generated from the DNA of a virus. The truly dangerous part of many infectious viruses is the DNA they inject into host cells; and researchers have discovered that certain cells can be trained to respond directly to that DNA, without encountering the dangerous organism as a whole.
In light of this fact, several labs have created vaccines that introduce viral DNA to the body’s cells, triggering them to produce antigens that signal the immune system to fight the virus; effectively turning the patient’s body into its own automated vaccine factory. As an added bonus, this naked DNA carries none of the risks of an attenuated virus, since it lacks the biological structure necessary to create an infection.
While many nucleic acid vaccines are still in the experimental stage, a few have already entered clinical trials, and several others are currently ramping up to that stage.
A further experimental innovation in nucleic acid vaccines comes in the form of recombinant vector vaccines, which use attenuated viruses (known as “vectors”) to introduce DNA to the body. The DNA these viruses deliver is not the full genome they carry in their infectious form, but an artificially engineered (recombinant) DNA strain designed to trigger the release of antigens that stimulate an immune response.
Since the attenuated vector viruses closely imitate the process of infection, they tend to stimulate stronger and longer-lasting immune responses than those elicited by nucleic acids on their own. And since they carry little or none of the DNA of an infectious virus, they come with extremely low risk of harmful mutation or infection.
Recombinant vaccines are currently in development for HIV, measles and rabies; and many more will soon be entering the development stage.
As alternatives to attenuated and inactivated viral vaccines continue to proliferate, forward-thinking pharma developers and contract manufacturing organizations (CMOs) will receive numerous opportunities to create and profit from emerging clinical-stage niches. Partnerships between developers and CMOs will prove increasingly crucial as this sector grows in breadth and complexity.
In addition to being a writer and speaker, Raymond E Peck is the Founder and CEO of VxP Pharma Services and VxP Biologics, both based in Indianapolis Indiana.