Monday, March 04, 2013

Genetically engineered vaccines and their potential risks.

Environmental Effects of Genetically Engineered Vaccines?
Terje Traavik
University of Tromsö
Norwegian Institute of Gene Ecology, Tromsö, Norway

Some types of genetically engineered or modified vaccines that are now being developed pose potential ecological and environmental risks. Such vacines may soon be in widespread use. The risks and hazards are most certainly within the realm of possibility, and according to the Precautionary principle they should be subject to preventive measures. In practice, however, the risks are considered to be non-existent, since they have not been supported by experimental or epidemiological investigations. This, again, is a "Catch-22" situation, in the sense that such investigations have not been performed at all.

At the present, the definition of "safety" is very narrow in vaccinology. "Safety research" is occupied with prospects of unintended and unwanted side effects with regard to the targeted vaccinees themselves, or nontargeted individuals within the same species. This narrowing of conception and research strategies may leave potential hazards unapprised until they actually happen.

The main purpose of this paper is to raise awareness and catalyze discussions. If this in its turn may contribute to having resources available for public funding of independent research, the efforts of the author have been well rewarded.

Immunity and vaccination.
Vaccination is a form of prevention or prophylaxis of infectious disease and cancers. The reasons for giving priority to prevention and prophylaxis are stronger than ever, as development of resistance in microorganisms, viruses and cancer cells are reducing the therapeutic opportunities offered by chemotherapeutics and antibiotics.

Through their continual battle with microorganisms and viruses, vertebrates have evolved an elaborate set of protective measures collectively termed the immune system. Infection with a specific disease agent may initiate immunity to that agent, and an individual that is immune to a specific infectious agent will be left unharmed when infected by that agent again.

Vaccination intends to provide individuals with immunological protection before an infection actually takes place. However, the immune system is very complex, and immunity against different infectious agents is based on fine-tuned balances between the various types of cells, signal substances and antibodies that make up the total immune system. For some disease agents cellular immune reactions are more important, for others specific antibodies are essential for protection. Because vaccination against a threatening disease may take place many years before exposure to the disease-causing agent, immunological memory is a critical factor. A long-lived immune response that may be mobilized and augmented rapidly when called for is essential. Furthermore, local immunity on the epithelial surfaces that are the portals of entrance to the body for most infectious agents is very important.

Until recently, most traditional vaccines were of the "whole disease agent"-type: after varying degrees of purification, the whole bacterial cell or virus particle was used for immunization. Such vaccines might be killed, inactivated or "live".

By modern techniques, "killed" vaccines may be based on single proteins purified extensively to constitute safe preparations with seemingly no side effects. However, in general such vaccines have given short-lived general immune responses, and weak local immune responses. This may, however, be due to rather crude and inadequate delivery systems for such vaccines.

Live vaccine agents infect the vaccinees, but have had their disease provoking abilities attenuated. "Live" vaccines often give stronger mobilization of all effector parts of the immune system, and in many instances also good local immunity. The most prominent drawback of such vaccines is that they may revert to their full disease-causing potential.

Genetically engineered vaccines and their potential risks.
Synthetic and recombinant vaccines are produced under contained conditions. Only a polypeptide which may confer protective immunity to a given disease agent are brought out of the production unit and used as vaccine. Such vaccines carry the same advantages and disadvantages as traditional "killed" or "subunit" vaccines. It is conceivable that new vaccine delivery systems and basic knowledge about immune system interactions will make these vaccines more efficient in the near future. It is difficult to imagine such vaccines posing ecological and environmental risks.

Genetically modified viruses and genetically engineered virus-vector vaccines carry significant unpredictability and a number of inherent harmful potentials and hazards. The immunological advantages of such vaccines are related to the fact that the viruses are "live" and infect the vaccinated individuals. It has, however, been demonstrated that minor genetic changes in, or differences between, viruses can result in dramatic changes in host spectrum and disease-causing potentials. For all these vaccines, important questions concerning effects on other species than the targeted one are left unanswered so far. The opportunity of a genetically engineered vaccine virus to engage in genetic recombinations with naturally occurring relatives is another unpredictable option. The new, hybrid virus progenies resulting from such events may have totally unpredictable characteristics with regard to host preferences and disease-causing potentials. Furthermore, when genetically modified or engineered virus particles are broken down in the environment, their nucleic acids will be released, representing the same unpredictable risk potentials as the DNA and RNA vaccines discussed below.

Much basic work is needed before recombinant bacterial vectors may be taken into practical use. For instance, it was recently demonstrated that genetically engineered bacteria might transfer their new gene efficiently to indigenous bacteria in the mammalian gut. This potential risk has not been investigated for bacteria that are now being genetically engineered as oral vaccines.

Naked DNA vaccines are engineered from general genetic shuttle vectors. They are constructed to break species barriers. Naked DNA may persist much longer in the environment than dogmas held just a short time ago. Consequently, upon release or escape to the wrong place at the wrong time, horizontal gene transfer with unpredictable long- and short-term biological and ecological effects is a real hazard with such vaccines. There is also growing concern about harmful effects due to random insertions of vaccine constructs into cellular genomes in target or non-target species.

RNA vaccines may have a far way to go before any of them find practical use. Although easy degradation is a serious problem with RNA work in the lab, RNA may be surprisingly resistant under natural conditions. At the present time recombination between related RNA molecules has become a real concern. RNA recombination is far more common than dogmatic views held until recently.

Genetically engineered plants produce "edible vaccines". Little is known about the consequences of releasing such plants into the environment, but there are examples of transgenic plants that seriously alter their biological environment. A number of unpredicted and unwanted incidents have already taken place with genetically engineered plants.
Some environmental pollutants (xenobiotics, i.e. PCBs, dioxins, heavy metals) may interact with genetically engineered vaccines, adding to their unpredictability and the inability to perform meaningful risk assessments

Final remarks
Changes in attitudes among scientists, medical doctors as well as politicians are badly needed. Recent experiences ought to call for humility with regard to environmental effects of science and technology. In many cases, "experts" were proven wrong after damage had been done. To the extent that any prior investigations of damaging effects had been undertaken, methods used were inadequate and only capable to reveal short-term effects, whereas the long-term impacts were the most important and serious.

There is a most striking lack of holistic and ecological thinking with regard to vaccine risks. This seems to be symptomatic for the real lack of touch between research in medicine and molecular biology on one hand, and potential ecological and environment effects of these activities on the other.

In order to make reliable risk assessments, perform sensible risk management with regard to genetic engineering in general, and genetically engineered vaccines in particular, much pertinent knowledge is lacking. The prerequisite for obtaining such knowledge is science and scientists dedicated to relevant projects and research areas. It must be the responsibility of the national governments and international authorities to make funding available for such research. On one hand, this is obviously not the responsibility of producers and manufacturers. On the other hand, risk-associated research must be publicly funded in order to keep it totally independent, which is an absolute necessity for such activities.

Vaccinology is the "Holy Grail" of medicine. Nevertheless, there are other ways of preventing infectious diseases in humans and animals, and these should not be ignored. Many of the most burdening infectious agents of mankind and its domesticated animals are caused by pathogens that have reservoirs and are circulating among wildlife animals. By increasing our knowledge about these reservoirs, their occurrence, the transmission routes within and out of the indigenous ecosystems, we might be able to break transmission chains, or keep our activities out of dangerous ecosystems. There is a void in knowledge about the ecological interactions of many important pathogens. This field is to some extent subdued by the confidence in vaccines, and hence it is a scientific orphan.

Selected reading.
A number of relevant references are given in:
Traavik, T. An Orphan in Science: Environmental risks of Genetically Engineered Vaccines. Research Report for DN 199-6. Directorate of Nature Management, Trondheim, Norway, 1999.

1 comment:

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