David Shelburne

The History & Future of Vaccinations

Humans have always had a great fascination with the world around them and the scientific explanation for the phenomena that affects their lives. Disease and sickness have plagued man since his origin, and man has always sought a way to remedy the contracted ailment. As humans progressed and advanced their medical treatments for diseases, the idea arose, “What if we can not just treat the ailment, but prevent the contraction of the disease altogether?” This idea led to the discovery of vaccines, which revolutionized the medical healthcare system. Advancements in techniques and knowledge of viruses and pathogens have led to a plethora of new and more effective vaccines. With the advent of genetically modified organisms, scientists are now beginning to see a potential breakthrough in the production of vaccinations. Genetically modified organisms (GMOs) exhibit potential for revolutionizing and improving the current production methods of vaccines.

To provide some historical context of the history of vaccines we must begin with smallpox, which is one of the most notorious of all deadly diseases in the course of human history. During the 18^th century smallpox decimated populations [primarily infants and young children] and was as prevalent as cancer and heart disease are today (Scott 1999). Edward Jenner, a former military surgeon from Gloucestershire, England, treated numerous patients through variolation in order to decrease his patients’ susceptibility to smallpox (“Edward Jenner & Smallpox” 2002). Jenner had heard that milkmaids who contracted cowpox from the cows they milked were immune to smallpox (“Edward Jenner & Smallpox” 2002). Interested by this, Jenner began clinical studies on the smallpox patients he treated as the local doctor (Scott 1999).

According to the Jenner Museum, a milkmaid came to Dr. Jenner in May 1796 with a case of cowpox that she had contracted from her cow. Dr. Jenner decided to test out the truth of the folklore concerning the connection between cowpox and smallpox and conducted the first human clinical trial on the 8-year old son of his gardener. Jenner scratched the boy’s arm and rubbed contagious material from the milkmaid’s pox marks into the cut (“Edward Jenner & Smallpox” 2002). The boy developed a harmless case of cowpox, and was ultimately declared immune to smallpox (“Edward Jenner & Smallpox” 2002). Edward Jenner had just made one of the most important medical discoveries of all time. The word “vaccination” was coined by Jenner for the treatment against smallpox which was derived from the Latin word “vacca” which means “a cow” (Scott 1999). This form of prevention against smallpox was so successful and worked so well that the British government in 1840 banned any alternative prevention methods against smallpox (Scott 1999). The amazing thing is that Jenner made this discovery prior to knowing anything about viruses or how these vaccinations worked (Scott 1999). Edward Jenner, despite his lack of knowledge of how it worked, revolutionized the medical world to divert attention from the treatment of a malady to focus on the prevention of it altogether. Scientists years later would eventually discover how these vaccines work and why they are so effective.

Scientists now understand how Jenner’s methods worked and how a vaccine works in general. When the foreign particles from the pox mark were introduced into the body, the body commenced a primary immune response to attack the newly introduced viral particles (Purves et al. 1998). According to Purves, the body produces lymphocytes and antibodies to deal with a disease or the killed viral particles that are introduced. Lymphocytic T cells and B cells which are responsible for the humoral immune response act as memory cells for the antigen [vaccine] injected. Therefore, when a similar antigen enters the body, the T cells and B cells recognize it and immediately attack the antigen with lymphocytes and antibodies (Purves et al. 1998). The body then is able to attack this antigen or vaccine anytime that disease enters the body. A caveat of this approach is that it assumes that the person has a good immune system to defeat the weakened disease or killed viral particles that are introduced. This presents problems for immunodeficient people incapable of producing an effective immune response.

In the 19^th, 20^th, and 21^st centuries, scientists expanded on Jenner’s research and produced many different vaccination methods. Vaccines today typically are comprised of either infectious [live] or non-infections [killed] viral particles (Dimmock et al. 2001). Dimmock’s Vaccine: From Concept to Clinic says that the infectious particles, like the ones Jenner used, are similar to viral particles that undergo a process known as attenuation. Attenuated virulent strains [weakened viral strains] generate avirulent particles that only produce a mild case of the disease. Killed viral particles, however, do not cause a disease in the inoculated patient, but are disadvantageous since they are dead and are unable to multiply in the body. As a result, large or repeated doses of killed vaccines must be administered to create an effective immunization, which becomes very costly (Dimmock et al. 2001). Public concern of introducing a contagious avirulent strain has led to the creation of other vaccination methods to alleviate the fears of vaccines.

The two leading alternative methods to live attenuated or killed vaccinations are subunit vaccines and nucleic acid vaccines (Paoletti & McInnes 1999). Subunit vaccines are comprised of one or several antigens that have been purified from the infectious organism or through recombinant DNA (Paoletti & McInnes 1999). The antigens that scientists purify or create are known to be able to shield the body from the disease and are exploited through subunit vaccines (Paoletti & McInnes 1999). Hepatitis B is one such disease that needed an alternative and more efficient vaccination method (Weisse 1991). In the past, scientists used immune globulins to protect against hepatitis B, but it was not long lasting and only 75% effective (Weisse 1991). A subunit vaccine has recently been developed against hepatitis B through the discovery that envelope proteins of the virus produced serum antibodies that were capable of neutralizing the virus (Paoletti & McInnes 1999). As a result these antibodies could be used to protect against infection; however, these antibodies could only be obtained from infected patients so they could not be obtained in large quantities (Paoletti & McInnes 1999). Fortunately, scientists were able to use recombinant DNA technology and yeast to create the envelope protein and manufacture the serum antibodies in large quantities (Paoletti & McInnes 1999). One of the ultimate advantages of these subunit vaccines is that it is impossible for a virus to arise from these subunits of a live virus (Paoletti & McInnes 1999). This ideology is applied in another method of immunization known as nucleic acid vaccination.

The newest vaccination method using nucleic acids proves to be very promising and is being experimented for use against influenza, TB, malaria, HIV, hepatitis B, and HPV infections (Paoletti & McInnes 1999). According to Paoletti & McInnes, nucleic acid vaccines implement the genes that code for antigens that the immune response would attack. Scientists insert the cloned genes into plasmid vectors placed adjacent to a strong promoter region which are then subsequently introduced into the body. The DNA that is inserted will express these foreign antigens in the body which bring forth an appropriate immune response against the antigen. The wonderful thing about nucleic acid vaccines is that the development of the vaccine is simple and that they are the most efficient vaccine capable of producing a cytotoxic immune response. Issues that still challenge nucleic acid vaccines are the safety of injecting foreign DNA into a human as well as the inefficiency of the delivery of the DNA plasmids. To produce an effective immune response, large dosages of plasmids would be required (Paoletti & McInnes 1999).

The World Health Organization (WHO) has been the forerunner in trying to immunize the world against a handful of diseases and pathogens. In 1974, the WHO started the Expanded Program on Immunization, which sought to immunize the world against diseases like smallpox, tuberculosis, diphtheria, tetanus, poliomyelitis, measles, etc. (“The History of Vaccination” 2001). In 1980, with the success of smallpox vaccinations, the WHO announced that smallpox had been officially eradicated (“The History of Vaccination” 2001). The last case of smallpox occurred in 1977 in Ethiopia (Dimmock et al. 2001). This was the first major success for the WHO, and the organization expanded its scope to other diseases (Dimmock et al. 2001). The WHO then added vaccines for yellow fever, hepatitis B, and MMR (Measles, Mumps, and Rubella) to the worldwide coverage list. With the success of smallpox eradication, the WHO made the following goals: polio eradication by the year 2000; neonatal tetanus eradication by the year 1995; a 95% reduction in measles death by 1995; and a 90% reduction in measles cases by 1995 (“The History of Vaccination” 2001). The WHO has nearly succeeded with the eradication of polio and has largely reduced the number of deaths due to neonatal tetanus. Measles has nearly been wiped off of the North American continent, but still exists in other parts of the world (“The History of Vaccination” 2001). The World Health Organization and World Health Assembly have made great strides in their goal of worldwide viral control. As with everything else in the world, money is always a problem and getting vaccinations for the entire world is an economic strain. New methods need to be developed to decrease the cost and increase the production of vaccines in the world.

Understandably, one can comprehend how public concern might arise over rubbing a live disease into the forearm of a child. Even in more advanced forms there has always been a concern of possible infection through immunization (Dimmock et al. 2001). Vaccinations are often blamed for any coincidental illnesses that are contracted at the same time as the immunization or are harshly judged for the finite risk of side effects (Dimmock et al. 2001). The risk concerns skyrocket when babies and infants are the target age for a large portion of immunizations. Highly-protective parents are hesitant to insert a live or even killed virus into their healthy new baby. One problem is that since the immunizations work so effectively, the diseases that the newborns are immunized against are so rare that parents see these immunizations as unnecessary. Is the risk of contracting the disease through the vaccination larger than the risk of contracting the disease in general? For example, when polio was prevalent, children had a 1:100 risk of getting paralytic poliomyelitis and only a risk of 1:1,000,000 of contracting poliomyelitis through vaccination, but a multitude of parents were concerned about being the one unlucky person in 1,000,000 people (Dimmock et al. 2001). The inability of the public to acknowledge acceptable risks could lead one to think they are irrational. However, in 2002 a child would be much more likely to contract poliomyelitis through the vaccination. So, society needs to be aware of the risk concerns presented by vaccines and the disease and be able to weight the two risk factors side by side. Public misconception and lack of knowledge has always been a problem with anything related to the scientific field, and vaccine industries must find a way to soothe the concerns of the public (Dimmock et al. 2001). Genetically modified organisms may be one such field that will be able to pacify the concerns of the public and make vaccines more readily accepted.

The booming research being conducted with genetically modified organisms proves to be a promising method of solving the economic problems as well as other problems associated with vaccinations. The organisms that are most focused on for genetic modifications are plants due to reduced cost and lack of a direct relationship to humans (Giddings et al. 2000). Genetic modification can either produce transgenic organism which are genetically modified with foreign DNA or non-transgenic organisms which are genetically modified through alteration of their own DNA to over-express a certain protein for example. Since the plants would be producing vaccines by expressing the protein of a foreign virus, only transgenic organisms would be used for edible vaccines. Some methods, which produce transgenic organisms, are Agrobacterium tumefaciens mediated gene transfer, particle bombardment with a gene gun, and electroporation (Giddings et al. 2000). Ultimately the goal of any of these methods is to create genetically altered organisms that have newly inserted DNA which codes for the organism to produce a specific vaccine for the disease you are trying to immunize against (Giddings et al. 2000). There are plenty of problems associated with the organisms that are chosen to create a certain vaccine as well as the whole debate over whether genetically modified organisms should be created at all (Giddings et al. 2000). Greenpeace and other earth-saving associations see genetically modified organisms as very dangerous and are working hard to prevent the creation of these organisms (Langridge 2000). Despite the protests and controversy surrounding genetically modified organisms, research has continued, and vaccines are being created for a wide variety of diseases (Langridge 2000).

Current research has created many new vaccines for a wide variety of diseases through a wide variety of plant hosts. ProdiGene, a pharmaceutical company in Texas, has developed and tested an edible corn vaccine to protect pigs from transmissible gastroenteritis virus (TGEV). The company has conducted trials and has discovered that the vaccine is effective and capable of protecting the pigs against TGEV (Giddings et al. 2000). Other research has been focused on hepatitis B, which seems to be one of the main goals of the entire vaccine research program. Charles Arntzen of Texas A&M University successfully created the first edible potato vaccine for hepatitis B (Langridge 2000). The potato expresses the antigen for hepatitis B known as the hepatitis B surface antigen (HbsAg) (Giddings et al. 2000). Studies with mice have shown that the potato vaccine has produced a humoral immune response [B cells] when introduced orally (Giddings et al. 2000). This is a huge success for vaccinations and for accomplishing the goals of the World Health Organization.

The advantages of these edible vaccines greatly outweigh the disadvantages of creating these edible vaccines from GMOs. Production method costs should be a lot cheaper using GMOs in that current vaccine production usually requires developing vaccines in yeast or animal cells (Giddings et al. 2000). Once they obtain the vaccine, they still have to undergo costly purification methods to prepare the vaccine for human use (Giddings et al. 2000). One of the great advantages of using edible vaccines is that the vaccine can be eaten and does not need to be injected with a hypodermic needle (Langridge 2000). Hypodermic needles are not only costly and have certain disposal routines, but also are a vector for the transmission of other infectious diseases in the third world countries that would benefit most from edible vaccines (Langridge 2000). Another very obvious advantage of not using needles is that there is no pain involved with the introduction of the vaccine (Langridge 2000). Vaccine research has shifted from potatoes and other plants to focus on bananas (Langridge 2000). Bananas are advantageous in that they do not need to be cooked and grow readily in third world countries that greatly need these cheaper vaccines (Langridge 2000). Research is ongoing and unless organizations like Greenpeace halt the production of genetically modified organisms, the world will more than likely be using edible vaccines in the very near future after the extensive clinical trials that will be needed to get them approved.

From Edward Jenner rubbing material from a pox mark into a cut on a little boy’s arm to having plants produce specific vaccines for us through the alteration of a plant’s genetic material, society has come a long way with vaccines. Vaccines create a safer world for everyone, and organizations like the World Health Organization are attempting to make the world virus-free. Edible vaccines are preparing to revolutionize vaccines once again and make them even more effective and plentiful. From Edward Jenner to edible vaccines is—to quote Neil Armstrong—“one giant leap for mankind.” Scientists will continue to improve vaccines and make them more effective as well as widen the number of diseases they are capable of immunizing against. With the success of our scientists and with the backing of the World Health Organization, we are capable of living in safe environment free of harmful and devastating diseases.

Bibliography

Dimmock, N.J. et al. Introduction to Modern Virology. Fifth Edition. Blackwell Publishing. Williston, Vermont. 2001.

“Edward Jenner & Smallpox.” The Jenner Museum. 04 December 2002. <http://www.jennermuseum.com/sv/smallpox2.shtml>.

Giddings, G. et al. “Transgenic Plants As Factories For Biopharmaceuticals.” Nature Biotechnology. Vol. 16. November 2000. 29 September 2002.

Langridge, William H. R. “Edible Vaccines.” 20 September 2000. ScientificAmerican.com. 24 September 2002. <http://www.sciam.com/print_version.cfm?articleID=000A9962-D220-1C739B81809EC588EF21>.

Paoletti, L. C. & McInnes, P. M. Vaccines: From Concept to Clinic. CRC Press. Boca Raton, Florida. 1999.

Purves, W. K. et al. Life: The Science of Biology. Fifth Edition. Sinauer Associaties, Inc. Sunderland, Massachusetts. 1998.

Scott, Patrick. “Edward Jenner and the Discovery of Vaccination.” 28 July 1999. Department of Rare Books and Special Collections. University of South Carolina. 04 December 2002. <http://www.sc.edu/library/spcoll/nathist/jenner.html>.

“The History of Vaccination.” 2001. World Health Organization, Geneva. 04 December 2002. <http://www.who.int/vaccines-diseases/history/history.shtml>.

Weisse, Allen B., M.D. Medical Odysseys: The Different and Sometimes Unexpected Pathways to Twentieth-Century Medical Discoveries. Rutgers University Press. New Brunswick, New Jersey. 1991.