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GENETICALLY ENGINEERED & MODIFIED LIVE VIRUS VACCINES: PUBLIC HEALTH AND ANIMAL WELFARE CONCERNS

Michael W. Fox  BVetMed, PhD, DSc, MRCVS


As one who has followed developments in genetic engineering biotechnology for some years, I have become increasingly concerned over the use of modified live and genetically engineered (GE) vaccines in companion animals and farmed animals. Hundreds of thousands of cats have been injected with a non-adjuvanted recombinant rabies vaccine spliced with the canary pox virus used as a ‘vector’. According to Meeusen et al (2007) ‘Vectored vaccines are genetically modified organisms that have the genes responsible for encoding the desired antigens incorporated into the genetic code of a "carrier" organism. The vector is non-infectious to the recipient and transmits the desired immunizing DNA/gene to susceptible cell where the antigens are produced and presented to immune cells. The vector with the hybridized DNA is also called a chimera—having genes of two or more unrelated agents. The common vectors are capripox and canarypox viruses, adenoviruses and flaviviruses. These vaccines stimulate both antibody and cell mediated antibody and, coincidentally, immunize with one dose. A concern is that repeated vaccinations may result in immunity to the vector virus eliminating its ability to infect/transmit the desired genes to the immune system. Currently, several vectored vaccines are used in companion animals.

Some genetically engineered viral vaccines consist of chimera viruses that combine aspects of two infective viral genomes. One example is the live Flavivirus chimera vaccine against West Nile virus (WNV) in horses (PreveNile), registered in the United States in 2006. The structural genes of the attenuated yellow fever YF-17D backbone virus have been replaced with structural genes of the related WNV. Chimera avian influenza virus vaccines have been produced on a backbone of an existing, attenuated Newcastle disease virus vaccine strain to protection against wild-type influenza virus as well as against Newcastle disease virus.

 DNA vaccines are also being developed that consist of gene segments of infectious organisms. They are injected directly into cells for the production of the desired immunizing antigens. Intradermal injectors are used to deliver the DNA directly to the dendritic cells of the dermis. This system induces antibody and cell mediated immunity with a single injection and provides prolonged immunity. A DNA vaccine is being tested for feline leukemia virus. A DNA vaccine licensed with the USDA has been developed to protect horses against viremia caused by WNV. WNV infection, caused by a flavivirus belonging to the Japanese encephalitis virus complex, is enzootic in parts of Africa and Asia. It was first detected in 1999 in the US in an outbreak involving birds, horses, and humans in New York, subsequently spreading rapidly to many states.

 

 I was particularly concerned by research being conducted at Philadelphia’s Thomas Jefferson University, Jefferson Vaccine Center under the direction of a Dr. Matthias J. Schnell who co-authored a scientific paper entitled ‘Rabies virus-based vectors expressing human immunodeficiency’. The following is the Center’s own synopsis of the research and development that is underway at this institution:

Research interests of the laboratory are the development of novel vaccines and viral pathogenesis.

Vaccines: Our laboratory develops Rhabdovirus-based [Rabies] vectors as vaccines against other infectious diseases. We are particularly interested in using molecular adjuvants and other molecules to enhance antigen-specific immunity and manipulate and retarget immune cells.
Using different molecular approaches, we perform detailed studies of highly attenuated RVs expressing HIV-1 or SIV genes and analyze their immunogenicity in mice. Our most promising HIV vaccine candidates are currently being analyzed in a monkey model for AIDS.
Other approaches include using genetically modified RV G proteins or RV capsids to carry antigens of other pathogens as vaccines against Anthrax and Botulism.
We also seek to develop safer and more potent RV vaccines for wildlife and humans.

Pathogenesis: We are interested in understanding the interaction of rabies with the infected host at the molecular level. The molecular mechanism of rabies virus pathogenesis is not well understood, and our research analyzes the different functions of the rhabdoviral proteins (e.g. rabies virus) and their interactions with host proteins and the immune system.
Current projects are directed toward understanding:
- RV virus neurotropism and neuroinvasiveness: The transport of RV within neurons and the interaction of the RV phosphoprotein and glycoprotein with host proteins (receptors and transporter molecules)
- Immune responses of wild-type RV and RV-based vectors in the infected host (innate and adaptive)

GE virus developers Dongming Zhou, Ann Cun, Yan Li, Zhiquan Xiang, and Hildegund C. J. Ertl of Philadelphia's Wistar Institute, posted on line on June 22, 2006, (ARTICLE doi:10.1016/j.ymthe.2006.03.027 ) a report entitled  A Chimpanzee-Origin Adenovirus Vector Expressing the Rabies Virus Glycoprotein as an Oral Vaccine against Inhalation Infection with Rabies Virus. Their summary read as follows:

Rabies has the highest fatality rate of all human viral infections and the virus could potentially be disseminated through aerosols. Currently licensed vaccines to rabies virus are highly effective but it is unknown if they would provide reliable protection to rabies virus transmitted through inhalation, which allows rapid access to the central nervous system upon entering olfactory nerve endings. Here we describe preclinical data with a novel vaccine to rabies virus based on a recombinant replication-defective chimpanzee-origin adenovirus vector expressing the glycoprotein of the Evelyn Rokitniki Abelseth strain of rabies virus. This vaccine, termed AdC68rab.gp, induces sustained central and
mucosal antibody responses to rabies virus after oral application and provides complete protection against rabies virus acquired through inhalation even if given at a moderate dose.

(These researchers used rodents, dogs, and primates in their research, and cultures of chicken fibroblasts).

This is a brief sample of the kind of vaccine research and development that is now going on world-wide. The use of recombinant replication-defective, vectored vaccines that express the proteins of rabies virus raises several issues, and comes close on the heels of using modified adenoviruses, herpesviruses and pox viruses as delivery systems for foreign antigens in livestock and poultry vaccines, and in bait to vaccinate and immuno-contracept wildlife. (For details see OIE/world Organization fro Animal Health, Manual of Diagnostic tests and Vaccines for Terrestrial Mammals, 2008. www.oieint.com/eng/normes/mmanual/A_00099.htm)
In the US Government’s Agriculture Fact Book 98, the Animal and Plant Health Inspection Service ‘regulates the licensing and production of genetically engineered vaccines and other veterinary biologics. These products range from diagnostic kits for feline leukemia virus to genetically engineered vaccines to prevent pseudorabies, a serious disease affecting swine. With the pseudorabies vaccines, tests kits have been developed to distinguish between infected animals and those vaccinated with genetically engineered vaccines. Since the first vaccine was licensed in 1979, a total of 79 genetically engineered biologics have been licensed; all but 20 are still being produced. More than a half-century ago, there were perhaps a half a dozen animal vaccines and other biologics available to farmers. Now there are 2,379 active product licenses for these animal vaccines and other biologics and 110 licensed manufacturers’.

 

TABLE 1
Currently marketed veterinary vaccines against viral diseases.
(From Meeusen et al 2007)

Target pathogen Target animal Brand name(s)a Distributor Characteristic(s)
PCV2 Pigs Porcilis-PCV2 Intervet Inactivated baculovirus expressed PCV2 ORF2 protein; adjuvanted
PCV2 Pigs Suvaxyn PCV2 Fort Dodge Inactivated PCV1-2 chimera; adjuvanted
Pseudorabies virus Pigs Suvaxyn Aujeszky

Fort Dodge gE- and thymidine kinase-deleted marker vaccine
Classical swine fever virus Pigs Porcilis Pesti Intervet Baculovirus recombinant E2 protein without emulsion
Classical swine fever virus Pigs Bayovac CSF E2 Bayer Leverkusen Baculovirus recombinant E2 protein without emulsion
BHV-1 Cattle Bovilis IBR Marker Intervet Live or inactivated gE-deleted marker vaccine
Equine influenza virus Horses PROTEQ-FLU (European Union), Recombitek (United States) Merial Canarypox virus-vectored vaccine
WNV Horses PreveNile Intervet Live flavivirus chimera vaccine
WNV Horses West Nile-Innovator DNA Fort Dodge DNA vaccine
WNV Horses RECOMBITEKEquine WNV Merial Canarypox virus-vectored vaccine
MDV (HTV) and IBDV Poultry Vaxxitek HVT+IBD Merial Live recombinant chimera virus expressing VP2 gene of IBD on HTV virus
Newcastle disease virus Poultry NA Dow AgroSciences HN recombinant produced in plant cell lines (registered but not on market)
Newcastle disease virus Poultry Vectormune FP-ND Biomune Fowlpox virus vectored
Avian influenza virus (H5N1) and NDV Poultry   Intervet Chimera virus on NDV backbone; field trials in 2007
Avian influenza virus Poultry Poulvac FluFend I AI H5N3 RG Fort Dodge Chimera H5N3 virus, inactivated in oil-based adjuvant
Avian influenza virus Poultry Trovac AI H5 Merial Fowlpox virus-vectored H5
Rabies virus Wildlife, canines Raboral Merial Vaccinia virus recombinant
Rabies virus Cats Purevax Feline Rabies Merial Canarypox virus-vectored vaccine
Rabies virus Cats PUREVAX Feline Rabies Merial Canarypox virus-vectored vaccine
Feline leukemia virus Cats EURIFEL FeLV Merial Canarypox virus-vectored vaccine
Canine parvovirusl Dogs RECOMBITEK Canine Parvo Merial Modified live virus
Canine coronavirus Dogs RECOMBITEK Corona MLV Merial Modified live virus
Canine distemper virus Dogs RECOMBITEK rDistemper Merial Canarypox virus-vectored vaccine (HA and F antigens)
Canine distemper virus Fur animals PUREVAXFerret Distemper Merial Canarypox virus-vectored vaccine
IHN virus Salmon Apex-IHN Novartis (Aqua Health) DNA vaccine

a Brand names may differ between countries. NA, not applicable.
NB. In June, 2009 the USDA/APHIS gave Intervet/Schering-Plough Animal Health a conditional license to sell a killed viral vaccine for use in dogs against the type A, subtype H3N8 canine influenza virus.

 

REVISITING VACCINATION NEEDS AND SAFETY
The first vaccine was Jenner’s cow pox (vaccinia) that gave protection to a related human virus, small pox (variola) when injected into the skin. This practice of dispensing a mild infection in the form of a vaccine, to give protection against a more virulent, natural strain is an ancient one. Maasai and other African herders would make small incisions on healthy cattle’s thighs and shoulders and then rub in a paste that included the secretions from sores of infected animals suffering from diseases like rinderpest, a virus closely related to measles and canine distemper viruses.
 Jenner’s discovery was a rare instance of cross-resistance, since subsequent vaccines did not have a less harmful related virus to use but instead were usually composed of killed organisms of the same natural infective virus or bacterium to induce an immune response. A few safe and effective vaccines were developed to give protection from tetanus and diphtheria using the inactivated toxins from these bacteria.
   More recently, weaker, so called attenuated, modified live virus (MLV) strains of the same species have been developed that ideally trigger specific antibodies and an immune system ‘memory’ to enable recipients to fight off infection. Immunocompromised individuals might get the disease from the actual MLV. Until recently, most vaccines were given by injection, a route that was actually abnormal and possibly problematic, especially when adjuvants like mercury and aluminum were included in the antigen cocktail. Safer, more natural routes are via ingestion or inhalation, this latter route being the focus of new vaccine research and development, especially for use in farmed animals in confined housing systems. But since natural infectious viruses tend to mutate, the strain used in the vaccine may not prove effective, or gives incomplete protection so that the recipient becomes a carrier or succumbs to the new infection.

Already we have seen MLV vaccines infect non-target recipients, like nursing infants via the milk of recently vaccinated mothers. Some virologists believe that the feline distemper or panleukopenia virus mutated and crossed over from cats, or from some unidentified wild carnivore, to become canine parvovirus when it infected dogs. There is now a strain of canine parvovirus (CPV) that can infect cats with a similar disease.  Vaccines can be contaminated by other virus strains, abortions and deaths being reported in pregnant bitches receiving a commercial canine parvovirus vaccine that was inadvertently contaminated with blue tongue virus of sheep.

In July 2009 the World health Organization reported several outbreaks of a mutated strain of poliomyelitis in children identified as causing paralysis and coming from children given the oral, modified live vaccine that they shed in their urine and feces and infected unvaccinated children.

IN-FIELD PROBLEMS WITH VACCINES
The interactions between administering and receiving vaccinations and existing viral infections in animal populations can be complex and have harmful outcomes. Wildlife biologist Dr Roger Burrows (personal communication, May 13, 2009) writes that   ‘Lions in Serengeti National Park (SNP), followed by those in the Masai Mara of Kenya, died like flies in 1994 from a new strain of canine distemper (CD). This followed a  period 1992-94 when domestic dogs of agropastoralist/farmers to the west, and Maasai pastoralists dogs to the east  of the SNP boundaries were being experimentally vaccinated against rabies during a vaccination trial .The same new strain of CD in the rabies vaccinated domestic dogs was subsequently found in the lions and was then found to have caused the death from CD of most of a captive colony of wild dogs ( Lycaon pictus) in Mkomzai Game Reserve in Tanzania in 2000-2001 - these wild dogs had been vaccinated against CD  (using an inactivated strain developed for North Sea Seals!).
Following this, in 2007 the same new CD strain was for the first time identified in free living African wild dogs in Maasai areas to the east of SNP where mass vaccinations of local domestic dogs were being carried out against CD, CPV and rabies. The outbreak confirmed in one large wild dog pack was associated with high mortality of this highly endangered canid species.’
When local breeds of domestic dogs around Serengeti National Park (SNP) and the Masai Mara of Kenya were vaccinated against rabies and then soon after succumb to a virulent outbreak of CD it would seem to indicate that the rabies vaccinations caused some immunosuppression and thus increased susceptibility to CD. Attenuated vaccines should not be given to stressed and immunocompromised animals or humans.
Giving multivalent vaccines such as attenuated CD and CPV together could also be problematic, where one could make the other revert to a more virulent form due to the kind of reaction by the recipient to the other vaccine. Sensitization may occur following vaccination, and subsequent vaccinations could cause an acute inflammatory reaction, the so called cytokine storm, which could be fatal.

VACCINE ADJUVANTS
The inflammatory response to vaccinations, for which adjuvants have been blamed, is associated with the development of injection-site fibrosarcomas in cats and also dogs.

While the move toward developing adjuvant-free vaccines in order to minimize harmful side-effects (such as vaccine hypersensitivities, and mercury exacerbating preexisting autoimmune disease), they are still widely used. They are thought to enhance the immune response for small protein and glycoprotein antigens that elicit a weak immune response alone, by direct stimulation of the immune innate response (inducing local inflammatory reactions and stimulating the nonspecific proliferation of lymphocytes).
Aluminum salt and water/oil emulsions adjuvants are used in food animal vaccines, but can lead to granulomas developing at injection sites Particulate or microsphere adjuvants are in limited veterinary usage in companion animal vaccines. They are made of biodegradable polymers that allow for a slow release of the antigen to the immune system.
Immunostimulatory complexes, (ISCOMS) are being developed and have been introduced into companion animal vaccines. They consist of a complex matrix of saponins, phospholipids and cholesterol incorporating the selected antigen. Their particulate structure enhances their interactions with antigen processing cells. ISCOMS tend to localize in lymph nodes draining the injection site prolonging the immune response, and can be administered at mucosal surfaces enhancing local antibody responses. Glycoside products called Quill A from the Chilean soap bark tree, and saponins are used in some companion animal vaccines. Being quite toxic these adjuvants require extensive purification to minimize toxicity.
VIRUSES EVOLVE AND MUTATE
Now that we have the new influenza viral strain that on its evolutionary journey in pigs and poultry has killed wild birds, humans, dogs, and cats, we should honor the nature of viruses. And most importantly, not fight them with vaccine cocktails of antibodies with or without adjuvants, which can make recipients extremely ill, and even die. The latest influenza viral strain A/H1N1 isolated in human patients in the US has a genetic sequencing indicating recombination of North American swine influenza, human influenza, avian influenza and Eurasian swine influenza virus.

As a veterinarian I am concerned over the widespread dissemination of MLV and GE virus strains through the mass vaccinations of humans, livestock and poultry, and in-house companion animals. Some GE vaccines have been widely used is several countries in bait to stop rabies in foxes, jackals, and other wild carnivores. These vaccines all contain live viruses, supposedly weakened strains recombined, like the pox virus used as an infective carrier, sliced with an attenuated strand of rabies virus DNA. It’s like the Cauliflower mosaic virus that is used as a carrier of engineered genes in GE crops expressing herbicide tolerance and insecticidal proteins (Bt in corn). But there is one big difference.  The aim of vaccination is to trigger an antibody immune response to the antigens in the vaccine. A poor response could lead to actual disease from the vaccine or vaccine failure, just as an over-reaction could mean death to the recipient. Virologists recognize that a gap of at least 3-4 weeks is desirable between giving one vaccine and then a different one, because if not so spaced the immune response to the second vaccine may be inadequate and not produce sufficient specific antibodies to give immunity. If there is a dormant/latent viral infection already present in the recipient, vaccination against another pathogen could impair the immune system leading to the latent viral infection taking hold. This may be the case in cats, for example, who can come down with feline leukemia or herpes virus infections after receiving a feline distemper or rabies vaccine. A similar process might have been going on in the wildlife and village dogs outlined above by Dr. Burrows.

VACCINOSES-ADVERSE VACCINE REACTIONS
This is the roulette of vaccine-based preventive medicine. It has become an industry that we are learning to censor because of the increasing incidence of adverse vaccine reactions, so called vaccinosis, in human and companion animal recipients. Selling annual vaccinations along with manufactured, highly processed pet foods has become the bread and butter of conventional small animal veterinary practice. Yet this combination, as in the consumer populace eating junk and convenience foods and being hypervaccinated in childhood, is the cause of a host of iatrogenic health problems, compounded by genetic susceptibility in certain pure-breeds.

 Veterinarian Dr. Jean Dodds has linked the following health problems in dogs to vaccinations that can harm some breeds more than others and appear more randomly in the ‘mixed breed’ segment of the population: fever, stiffness, sore joints and abdominal tenderness, neurological disorders, polyneuropathy, transient seizures, and encephalitis, increased susceptibility to infections, collapse with autoimmune hemolytic anemia, immune mediated thrombocytopenia, immune-mediated hemolytic anemia, autoimmune thyroiditis, necrotizing vasculitis, joint disease, polyarthritis, and hypertrophic osteodystrophy.

 While acknowledging other environmental factors, Dr. Dodds contends that the increase in allergic and immunological diseases in dogs is linked to the introduction of MLV vaccines more than 20 years ago. Cats generally fare better, injection-site fibrosarcomas, occasionally reported also in dogs, being the major adverse vaccine reaction that is usually fatal. What role vaccines play in the genesis of various other cancers in animals and humans remains to be determined.
A team at Purdue University School of Veterinary Medicine conducted several studies to determine if vaccines can cause changes in the immune system of dogs that might lead to life-threatening immune-mediated diseases such as lupus and glomerulonephrosis. The vaccinated, but not the non-vaccinated, dogs in the Purdue studies developed autoantibodies to many of their own biochemicals, including fibronectin, laminin, DNA, albumin, cytochrome C, transferring, cardiolipin and collagen.
Autoantibodies to cardiolipin are frequently found in genetically susceptible patients with systemic lupus erythematosus, and also in individuals with other autoimmune diseases. The presence of elevated anti-cardiolipin antibodies is significantly associated with cardiomyopathy.
The Purdue finding that vaccinated dogs were developing autoantibodies to their own collagen that provides struc­tural stability to joints helps explain the high incidence of torn crutiate ligaments in dogs, and the UK Canine Health Concern's 1997 study of 4,000 dogs that showed a high number of dogs developing mobility problems shortly after they were vaccinated ( see Catherine O’Driscoll’s 1997 book, What Vets Don't Tell You About Vaccines).
The World Small Animal Veterinary Association WSAVA) guidelines include the statement that “dogs that have responded to vaccination with MLV core vaccines (parvovirus, distemper virus and adenovirus) maintain immunity (immunological memory) for many years in the absence of any repeat vaccination”. The 2007 WSAVA guidelines specifically warn that core vaccines should not be given any more frequently than every three years after the 12 month booster injection following the puppy/kitten series. The American animal Hospital Association's Canine Vaccine Task Force in 2003 noted that MLV vaccines are likely to provide lifelong immunity, stating “when MLV vaccines are used to immunize a dog, memory cells develop and likely persist for the life of the animal”.

The U.S Department of Agriculture and the American Veterinary Medical Association (AVMA)   are addressing the problem of vaccine product labeling that make “false and misleading” claims. Notably the AVMA has urged that recommendations for revaccination should be removed from vaccine labels where the statement lacks a scientific basis. It is also to be noted that manufacturers do not always list all ingredients in their products, claiming proprietary interest.
Humans and other animals with inherited faulty B and/or T cell immunodeficiencies should not receive live-virus vaccines due to the risk of severe or fatal infection. B and T cell immunodeficiencies are also associated with food allergies, inhalant allergies, eczema, dermatitis, neurological deterioration and heart disease.
 Dog breeds vary in the titers they develop following vaccination, a low titer not necessarily meaning poor immunity because of other components of immune defense mechanisms that blood titers do not measure, including mucosal immunity, cell-mediated immunity, and immune memory ells. The innate immune system modulates the quality and quantity of long-term T and B cell memory and protective immune response to pathogens.
Patients on NSAIDs and other anti-inflammatory drugs may not produce a good antibody response to vaccinations, while prior sensitization of dogs with an allergen such as pollen can lead to hypersensitivity associated with excess amounts of IgE antibodies and subsequent chronic inflammation of the skin, conjunctivitis and rhinitis.
Long-term over-activation of the immune system, as through hyperimmunization with repeated annual ‘booster’ vaccinations, may be a major cause of cancer. Smith and Missailidis (2004) have proposed that inflammation could prevent the body from recognizing a foreign substance and may therefore serve as a hiding place for invaders. Cancers are like wounds that never heal and are surrounded by inflammation. This is generally thought to be the body's reaction to try to fight the cancer, but this may not the case. The inflammation is not the body trying to fight the infection. It is actually the virus or bacteria deliberately causing inflammation in order to hide from the immune system. That dogs surpass humans in the incidence of certain cancers raises the probability of hyperimmunization with MLVs which is a widespread practice in the US, the UK, Australia and many other countries.

THE BEHAVIOR AND ECOLOGY OF VIRUSES
Even seemingly harmless viruses like the coxsackievirus can become virulent in selenium-deficient human hosts. Stress and malnutrition go hand in hand, impairing the immune system’s ability to respond effectively against viral infections---and even against weaker strains in vaccines that then convey no immunity. Given this extreme variability of viruses that proliferate more as population densities increase, especially down on the CAFOs---confined and crowded animal feeding operations for pig, poultry and cattle industry “farms”, we should not be adding to the genetic diversity of the viral community by introducing live GE vaccines. The same reservations hold true for the ‘philanthropic’ vaccination programs in the urban slums and impoverished rural communities where humans, rats, rabid dogs, and Ebola virus- and AIDS virus-carrying monkeys are part of the inter-species matrix for viral proliferation and evolution.  We must look to safer and in the long term less costly solutions by addressing the ecology and behavior of infectious viruses.

The kinds of viral research going on today, including applications in biowarfare, are primarily driven to develop new vaccines to market in the name of ‘preventive’ human and veterinary medicine. The risks of genetically engineering new vaccines are considerable. Pair the release of such GE vaccines into the environment with the recent reporting of the rabies virus rapidly evolving in Arizona and other parts of the US. It is cross-infecting bats, foxes, and skunks, and health authorities are rightly concerned that the virus could soon jump into the human population, like the Hanta virus, and West Nile virus. Adding attenuated live vaccines into such a pathogenic milieu is counter-intuitive.

 Using the proteins expressed from the rabies virus DNA, albeit replication-defective, and splicing it on to a highly attenuated avian influenza virus for manufacture and use by the poultry industry world wide is patently absurd in terms of potential risks and ultimate costs. Widespread vaccinations against one infectious strain may open the door for the proliferation of a different pathogenic virus, as in the viral epidemic-vaccine associated outbreaks of canine distemper and rabies in Maasai dogs and lions, wild dogs, and other endangered carnivore species. This is now being compounded by the spread of canine parvovirus into their communities.

MORE VACCINES TO COME
The development of vaccines and biowarfare agents that can be dispensed as aerosols or nose-drops, (in part justified in order to reduce adverse reactions to adjuvants in injected vaccines that can cause cancer and other diseases), has obvious military value. But such aerosol vaccines, like those of pig brains in mid-west slaughter houses that caused neurological disease in several workers, include foreign proteins that could trigger neurological and auto-immune diseases, allergic reactions and anaphylactic shock.
DNA vaccines that purportedly need no cold-chain preservation, are normally bacterial plasmids into which are spliced a promoter active in mammals, such as the cytomegalovirus promoter. This drives the coding sequence for an antigen. The plasmid is taken up by the mammalian cells and reaches the nucleus of some of those cells. There it is transcribed into RNA, which is translocated to the cytoplasm and translated into antigen protein. DNA vaccines induce a full spectrum of immune responses. These include antibodies, cytotoxic T lymphocytes, and T helper cells. Concerns have been expressed over the induction of autoimmunity and anti-DNA antibodies, which were observed in rabbits immunized with plasmids bearing a HIV reverse transcriptase gene.
Chan (2006), following up on the earler concerns expressed by T. Travik  writes: ‘Despite major therapeutic advances, infectious diseases remain highly problematic. Recent advancements in technology in producing DNA-based vaccines, together with the growing knowledge of the immune system, have provided new insights into the identification of the epitopes needed to target the development of highly targeted vaccines. Genetically modified (GM) viruses and genetically engineered virus-vector vaccines possess significant unpredictability and a number of inherent harmful potential hazards. For all these vaccines, safety assessment concerning unintended and unwanted side effects with regard to targeted vaccinees has always been the main focus. Important questions concerning effects on nontargeted individuals within the same species or other species remain unknown. Horizontal transfer of genes, though lacking supportive experimental or epidemiological investigations, is well established. New hybrid virus progenies resulting from genetic recombination between genetically engineered vaccine viruses and their naturally occurring relatives may possess totally unpredictable characteristics with regard to host preferences and disease-causing potentials. Furthermore, when genetically modified or engineered virus particles break down in the environment, their nuclei acids are released. Appropriate risk management is the key to minimizing any potential risks to humans and environment resulting from the use of these GM vaccines. There is inadequate knowledge to define either the probability of unintended events or the consequences of genetic modifications.’
Many health professionals believe that the benefits of vaccinations far outweigh their risks, and some would like to legislatively mandate their dispensation. The middle ground as I see it is to address the misuse of vaccinations, their over-use, as well as fully determine their safety and effectiveness (as with Lyme disease, Bordetella and Leptospirosis vaccines in dogs, and the use of multivalent MLV and GE/MLV vaccines in both dogs and cats); and place priority on prevention.

Effective prevention must include understanding the ecology and behavior of viruses and other pathogens---immunology must include epidemiology and population densities and dynamics, as distinct from vaccinology, the research and development of vaccines that may wrongly prioritize vaccinations in the medical paradigm of disease prevention. The widespread dissemination of live GE viruses is a very costly, high-risk, low health priority that if not prohibited or controlled internationally could amount to a biomeolecular assault on the life community of planet Earth. It could, through viral mutations and non-target host transformations, lead to the devastation of human civilization, and to animal populations wild and domestic.

 Once again the military-industrial complex is in the process of unleashing the products of biotechnology, medical and agricultural, into the environment. A super-swine flu-modified virus spliced into a future GE vaccine could recombine in an AIDS-infected person to make the HIV virus transmissible though a single sneeze.

SAFETY AND CONSEQUENCES
Even if such government endorsed, pharmaceutical company funded, and ‘philanthropically’ supported institutions like the Jefferson Vaccine Center and Wistar Institute pass with flying colors on biosecurity, the actual biosafety of their new vaccines can only be really determined after they are released. The bioethics and biological consequences of these innovations have never been satisfactorily answered from a purely objective and scientific rather than profit-driven perspective. The same must be said with regard to the creation of vaccine-producing plants, like the potato with Hepatitis B oral vaccine that cooking will not destroy, and of genetically engineered and cloned farmed animals producing monoclonal antibodies in their milk and blood for use in ‘the war on cancer’ and other anthropogenic diseases. Developers of GE vaccines are gambling with life for primarily pecuniary ends especially when the use of such vaccines is the primary if not sole response to potential pandemics and to the challenges of public health and disease prevention.

 The misanthropy behind commercial vaccinology is more of consequence than design. Or so I wish to believe. The new generation of live GE vaccines being developed, tested and marketed could amount to a chaos-sustaining genetic pollution that will predictably be far worse than radioactive ‘waste’, because it will be impossible to ever recall or contain. There are enough DNA damaging pollutants in our food, water and air which need to be cleaned up as it is. Indirectly profiting from the health problems these are causing with ever more pharmaceutical and other conventional, often iatrogenic, medical treatments is ethically questionable. Infections to a large extent are anthropogenic, and so disease control has always been best achieved through such common sense reduction of exposure risk, good hygiene, mechanical barriers/quarantine, and assuring good nutrition and healthy (especially non-crowded) environments.

 Above all, natural ecosystems must receive emergency CPR---conservation, preservation and restoration. Unhealthy, human-infested and degraded ecosystems are ideal environments for viruses to spill over from healthy carrier hosts, like bats who have brought us from their desecrated forests, the Hendra, Nipah and Ebola viruses that killed people and, respectively, horses, pigs and neighboring chimpanzees and gorillas. The Simian immunodeficiency virus spilled over into humans as HIV-1. Anthropozootic diseases (from the people to the wildlife) include polio, measles, influenza and tuberculosis. Vaccinations are neither the end-all of preventive medicine nor its proper foundation, but used with caution they may play a useful role in integrated (animal-human-environment) medicine and health care maintenance. The behavior of viruses would seem to make them an indicator species for us to monitor and understand for our own good rather than reflexively seek to eradicate, since they reflect dysfunctional ecosystems and animal and human communities and populations.

The author acknowledges with appreciation the helpful critique of Dr. W. Jean Dodds in the completion of this article.

 

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World Small Animal Veterinary Association Dog and Cat Vaccination Guidelines: http://www.wsava.org/PDF/Misc/VGG_09_2007.pdf

“The only safe vaccine is one that is never used.----No vaccine can be proven safe before it is given to children.”---statements by the late James A. Shannon, while serving as Director of the US National Institutes of Health.

 

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