Genetically engineered vaccines.
Genetically engineered vaccines
'Inherently unpredictable and possibly dangerous'
In recent years, genetically engineered vaccine strategies have been rushed into common use within such fields as medicine, veterinary medicine and fish farming. Some scientists contend that such vaccines are totally innocuous. But a recent and major research report by Professor Terje Traavik reduces the 'safe technology' to sheer naive optimism, and warns in conclusion that 'many live, genetically engineered vaccines are inherently unpredictable (and) possibly dangerous.' Martin Jalleh highlights the compelling findings of the report - which make the arguments for genetically engineered vaccines look frail and move Traavik to call on the scientific community to go beyond the 'Holy Grail' of medicine
MODERN molecular biology, recombinant DNA technology and genetic engineering have opened the road to a number of alternative strategies for vaccine production,' reveals Professor Terje Traavik of the Departments of Virology and Medical Microbiology, University of Tromso, GENK-Norwegian Institute of Gene Ecology, Tromso, Norway. He deems it necessary to add: '...from an ecological and environmental point of view many first generation live, genetically engineered vaccines are inherently unpredictable, possibly dangerous...' He emphasises that such vaccines 'should not be taken into widespread use until a number of putative problems have been clarified'.
He describes the risks and hazards as 'most certainly within the realm of possibility, and according to the Precautionary Principle they should be subject to preventive measures'. He points out, '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.'
According to Traavik, the report attempts to 'address the potential ecological and environmental risks posed by some types of genetically engineered (GE) or modified vaccines that are now being developed, and may soon be in widespread use'. (Most of the excerpts from Traavik's report quoted in this article and accompanying boxes refer to GE live virus vectors. Other quotations are either general in nature or refer specifically to naked DNA vaccines.)
Traavik's report prompts a rather pertinent question, which at the same time effectively brings to the fore the fact that genetically engineered vaccines are inherently unpredictable - does genetic engineering deserve the 'technology' label?
Unpredictable effects
According to Traavik, the word 'technology' is derived from the Greek term 'tekhne' which is connected to handicrafts or the arts. It is often associated with predictability, control, and reproducibility. He then goes on to say that 'the parts of genetic engineering that concern construction of vectors are truly technology.' On the other hand, and in contrast, he argues, present-time techniques for moving new genes into cells and organisms mean:
· No possibility of targeting the vector/transgene to specific sites within the recipient genomes. In practical terms, this means that modifications performed with identical ...
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Unpredictable effects
According to Traavik, the word 'technology' is derived from the Greek term 'tekhne' which is connected to handicrafts or the arts. It is often associated with predictability, control, and reproducibility. He then goes on to say that 'the parts of genetic engineering that concern construction of vectors are truly technology.' On the other hand, and in contrast, he argues, present-time techniques for moving new genes into cells and organisms mean:
· No possibility of targeting the vector/transgene to specific sites within the recipient genomes. In practical terms, this means that modifications performed with identical recipients and vector gene constructs under the same standardised conditions may result in highly different genetically modified organisms (GMOs) depending on where the transgenes become inserted.
· No control of changes in gene expression patterns for the inserted or the endogenous genes of the GMO.
· No control of whether the inserted transgene(s), or parts thereof, move within or from the recipient genome, or where transferred DNA sequences end up in the ecosystems.
Very few research reports concerning environmental or ecological effects of genetically engineered vaccines were published as late as January 1999. On the other hand, examples of scientists defending the total innocuousness of vaccines, without taking environmental and non-target effects into consideration, are numerous. Many seem totally religious in their belief, and prescribe strategies to convert the ignorant public and politicians,' Traavik observes.
'Furthermore, I suspect that the lack of holistic and ecological thinking with regard to vaccine risks is symptomatic of the real lack of touch between medicine and molecular biology on one side, and potential ecological and environmental effects of these activities on the other.
According to Traavik, genetically engineered self-replicating and/or self-expressing vaccines 'may turn out to be good equipment in science, but too dangerous for practical large-scale use'. It has also become evident to him that 'the various putative risk factors and hazards related to these vaccines ought to be adequately investigated before we and the ecosystems are massively exposed to them
He notes: 'With regard to development and commercialisation of genetically engineered nucleic acids, organisms and viruses, we often are neither able to define probability of unintended events nor the consequences of them.
Hence, the present state of ignorance makes scientifically based risk assessments impossible.' This, according to Traavik, calls for invoking the 'Precautionary Principle', the need for which, he believes, can hardly be overestimated, both for risk management and for generations of risk-associated research.
In the context of gene technology and use of GMOs, he says, the principle could be generally defined as follows: 'In order to obtain sustainable development, policies should be based on the Precautionary Principle
His findings on the strategies can be summed up as follows: 'Genetically modified viruses and genetically engineered virus-vector vaccines carry significant unpredictability and a number of inherently harmful potentials and hazards
He stresses that to the extent that any prior investigations of damaging effects had been undertaken, methods and approaches had been used that were only capable of disclosing short-term effects, whereas in ecological contexts it is the long-term impacts that are most important and most serious.
'Long-term impacts in these contexts, and also in connection with the possible damaging effects of the dispersal of genetically engineered vaccines means not months or years, but at least ten to hundreds of years,' Traavik warns.
Genetically engineered vaccines
BELOW are some GE vaccines referred to by Professor Terje Traavik in his report, An Orphan in Science: Environmental Risks of Genetically Engineered
Vaccines:
Subunit vaccines: They represent technologies ranging from the chemical purification of components of the pathogen grown in vitro to the use of recombinant DNA techniques to produce a single viral or bacterial protein, such as Hepatitis B surface antigen for example. The disadvantage of such vaccines is that immune responses, especially T-lymphocyte activation, are too weak.
DNA vaccines: They employ genes encoding proteins of pathogens rather than using the proteins themselves, a live replicating vector, or an attenuated version of the pathogen itself. They consist of a bacterial plasmid with a strong viral promoter, the gene of interest, and a polyadenylation/transcriptional termination sequence. The plasmid is grown in bacteria (e. coli), purified, dissolved in a saline solution, and then simply injected into the host. In present versions only very small amounts of antigens are produced within the vaccinated individual.
Recombinant (DNA) vaccines: Made by isolation of DNA fragment(s) coding for the immunogen(s) of an infectious agent/cancer cell, followed by the insertion of the fragment(s) into vector DNA molecules (i.e. plasmids or viruses) which can replicate and conduct protein-expression within bacterial, yeast, insect or mammalian cells. The immunogen(s) may then be completely purified by modern separation techniques. The vaccines tend to give good antibody responses, but weak T-cell activation.
Naked DNA vaccines: They are engineered from general genetic shuttle vectors and constructed to break species barriers. They may persist much longer in the environment than commonly believed. 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 may be harmful effects due to random insertions of vaccine constructs into cellular genomes in target or non-target species.
Live vector vaccines: These are produced by the insertion of the DNA fragment(s) coding for an immunogen(s) intended for vaccination into the genome of a 'non-dangerous' virus or bacterium, the vector. The insertion is performed in such a way that the vector is still infectious 'live'.
RNA vaccines: This involves the use of in vitro synthesised RNA (a single-stranded relative of DNA). RNA are different from DNA vaccines in that there is no risk of chromosomal integration of foreign genetic material.
Edible vaccines: These are produced by making transgenic, edible crop plants as the production and delivery systems for subunit 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.
CONSIDERING the unpredictability of genetically engineered vaccines, Professor Terje Traavik has come up with a list of questions which he feels have to be answered in a satisfactory way before any vaccinia virus vectored GE vaccines are released:
*Can the virus engage in genetic recombination, or by other means achieve new genetic material? If so, will the hybrid offspring have changed their host preferences and virulence characteristics?
*Can other viruses that are present within the ecosystem influence the infection with the released virus or its offspring? Can insects or migrating birds or animals function as vectors for the released virus or its offspring, to disseminate viruses out of their intended release areas?
*For how long can the virus and its offspring survive outside host organisms under realistic environmental and climatic conditions?
*Is the virus and its offspring genetically stable over time?
*Can the virus or its offspring establish long-lasting, clinically mute, persistent or latent infections in naturally accessible host organisms?
*Can the virus or its offspring activate or aggravate naturally occurring latent or persistent virus infections?
The stark reality, he points out, is that most of these questions are unaccounted for, when they are related to vaccinia virus vectored GE vaccines (VV). 'Even when they have been answered by experimental investigations, ecological non-target effects cannot be excluded because even carefully designed model studies will not directly reflect the real ecosystem conditions, which in addition are dependent on local variable parameters.'
Warning signals
PROFESSOR Traavik provides growing evidence of the unpredictability of GE virus recombinants:
*During the human small pox eradication campaign, vaccinia virus vectored GE vaccines (VV) found a new host species and established themselves in a new reservoir, namely the buffalo.
*It is a general experience that inserts may change the virulence and host preferences of viruses.
· MRV (Malignant rabbit virus) seems to be a recombinant between SFV (Shope fibroma virus) and myxoma virus. It seems to have arisen by mixed infection in wild rabbits. MRV causes an invasive malignant disease and profound immunosuppression in adult rabbits, much more serious than the diseases caused by any of the parental viruses. MRV has received more than 90% of its DNA from one parent (myxoma virus) in a coupled recombination and transposition event. The MRV story exemplifies the unpredictability of virus recombinants with regard to biological characteristics and virulence.
· A recombinant field isolate of capripoxvirus has also been detected. The new virus was the result of recombination between a capripoxvirus vaccine strain and a naturally occurring virus strain.
Source - www.twnside.org.sg
