Prevention Is the Best Medicine: Vaccines in the 21st Century

An ounce of prevention is worth a pound of cure. Benjamin Franklin’s words ring as true today as they did in 1736, and although he was referring to fire prevention, prevention is a central tenet of immunization programs.

The first evidence of vaccination is from the Chinese, who as early as 1000 CE were inoculating against smallpox by taking powdered smallpox scabs from people with the disease and blowing it up the nostrils of healthy people or rubbing it into superficial cuts in the skin.

In the 16th century, explorers reported on nomadic herders in Africa who were performing similar variolation techniques to protect their sheep from sheep pox. Although using smallpox to immunize humans and sheep pox to immunize sheep resulted in solid immunity in both populations, postinoculation mortality was high as a result of contracting the full virulent disease instead of an attenuated version. The modern age of vaccination has its origin with Edward Jenner, who in 1796 recognized that humans could be protected from smallpox using cowpox as the inoculant, which was significantly less dangerous.

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Following Jenner’s discovery, vaccine development intensified. Although more than 1900 veterinary vaccines against at least 60 diseases are registered worldwide today,^1-4 only a handful are considered core for companion animals and livestock. These vaccines are intended to protect our animals from infectious agents, be they viruses, bacteria, or parasites. However, new classes of vaccines against chronic diseases are under investigation. For example, a vaccine against canine melanoma (Oncept, Merial), introduced in the United States in 2010, was the first therapeutic vaccine for the treatment of cancer in either animals or humans.

Unlike traditional vaccines, which normally activate the immune system to protect against future disease, therapeutic vaccines activate the immune system to fight existing disease. There is even a vaccine to increase fertility in sheep that stimulates an immune response against the steroid androstenedione to decrease estrogen levels (Ovastim, Virbac; not available in the United States).

How Vaccines are Created

Another area under investigation is how vaccines are created. Traditional vaccines rely heavily on either attenuation or the killing of the whole pathogen to render it safe. With attenuated vaccines, a less virulent strain of the pathogen replicates in the host to promote an immune response, which sometimes leads to clinical signs of disease, especially in immunocompromised individuals. Inactivated (killed) vaccines cannot replicate inside an individual, so they do not cause clinical signs of disease, but some of these vaccines have been associated with sometimes severe immune-related adverse effects. To improve safety, recombinant technology is being used to create vaccines that are made from just the genes that code for those antigens that induce immunity. Similarly, specific genes related to virulence are being deleted from whole pathogens, making them less likely to cause disease but still capable of promoting an immune response. Genetic engineering is also being used to insert antigens from animal pathogens into plants, which then produce large amounts of the antigen to be used as a vaccine.⁵ (See Table^6-10 for a list of currently available vaccine types.)

Adjuvants

Adjuvants are used to boost immune responses and are a necessary component of inactivated vaccines. The use of adjuvants has its origins in the early days of vaccine exploration when Gaston Ramon developed an anti-tetanus vaccine in 1924 that combined the inactivated tetanus toxin with aluminum hydroxide after observing the varying effectiveness of different vaccine preparations in horses. Although aluminum-based vaccines have been around since that time, the exact mechanism behind how they work to boost immunity remains unclear. Aluminum-based adjuvants are safe in the majority of cases, but adverse reactions can occur, including fever, arthritis, uveitis, anorexia, soreness, lethargy, and injection-site sarcomas. Thus, investigations are ongoing to find safer and more effective adjuvants and to further expand the development of non-adjuvanted vaccines.

Veterinary medicine is actually ahead of human medicine in this area because any adjuvant destined for human use is tested first in animals. Adjuvants under development or in experimental and commercial vaccines beyond aluminum salts include oil emulsions, saponins, immune-stimulating complexes, liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. In addition, an adjuvant-free 3-year rabies vaccine for cats, which are particularly prone to injection-site sarcomas, was introduced to the market in 2014 (PureVax Feline Rabies 3 YR, Merial).

Alternative Delivery Methods

There is much interest in finding alternative vaccine delivery methods. A number of oral vaccines are commercially available, such as a coccidiosis vaccine for poultry that can be delivered through automatic waterers for mass vaccination (eg, Coccivac-B, MSD Animal Health) and a recombinant rabies vaccine administered to wildlife in sachets encased in fish meal bait (eg, Raboral V-RG, Merial). The aforementioned canine melanoma vaccine is administered transdermally by propelling the vaccine at high speeds through the skin via a proprietary device.

You most likely have administered an intranasal Bordetella vaccine to a cat or a dog; vaccines administered via this route are intended to mimic the course of natural infection. Similarly, ocular vaccines, such as a vaccine against Newcastle disease, are applied to the surface of the eye, which is a route of infection. Spray and topical vaccines, such as the ectoparasites vaccine for poultry, are used in mass-vaccination scenarios, but it is difficult to ensure that all animals are inoculated. Until vaccines delivered through alternative methods are proven as effective and safe as those given parenterally, the core vaccines, at least for companion animals, will be delivered via needle.

Vaccine Regulation

While the science of vaccines is evolving, encompassing new knowledge and technologies, the regulatory landscape is also changing based on these advances. For example, vaccines that target noninfectious disease (eg, cancer, fertility) fall under the more stringent authority of the FDA instead of the Department of Agriculture, which increases both time to approval and cost of development. Nevertheless, the value of vaccines for disease prevention is clear, and the pace of vaccine development will only increase as new illnesses come to light. As Bill Gates said, “Treatment without prevention is simply unsustainable.”

Meredith Rogers has a bachelor of science degree in animal health from the University of Connecticut and a master of science degree in microbiology and molecular genetics from Rutgers University. She has more than 19 years of experience creating content for a variety of health care audiences. She lives in Kingston, New Jersey, and shares her life with a horse, a dog, and a cat.

References:

• The Vetvac resource. Vetvac.org website. http://vetvac.org. Accessed September 4, 2017.
• Compendium of veterinary vaccines for transboundary diseases. Center for Food Security & Public Health website. www.cfsph.iastate.edu/Vaccines. Accessed September 4, 2017.
• Canine and feline vaccination guidelines. UC Davis Veterinary Medicine website. www.vetmed.ucdavis.edu/vmth/small_animal/internal_medicine/newsletters/vaccination_protocols.cfm. Revised April 2017. Accessed September 4, 2017.
• Core vaccination guidelines. American Association of Equine Practitioners website. https://aaep.org/guidelines/vaccination-guidelines/core-vaccination-guidelines. Accessed September 4, 2017.
• Scotti N, Rybicki EP. Virus-like particles produced in plants as potential vaccines. Expert Rev Vaccines. 2013;12(2):211-224. doi: 10.1586/erv.12.147.
• US Department of Health and Human Services. Types of vaccines. Vaccines.gov website. Reviewed July 26, 2017. Accessed September 20, 2017.
• Meeusen ENT, Walker J, Peters A, Pastoret PP, Jungerson G. Current status of veterinary vaccines. Clin Microbiol Rev. 2008;20(3):489-510. doi: 10.1128/CMR.00005-07.
• Coban C, Kobiyama K, Jounai N, Tozuka M, Ishii KJ. DNA vaccines: a simple sensing matter? Hum Vaccin Immunother. 2013;9(10):2216-2221. doi: 10.4161/hv.25893.
• Biologicals: DNA vaccines. World Health Organization website. www.who.int/biologicals/areas/vaccines/dna/en/. Accessed September 20, 2017.
• Nascimento IP, Leite LC. Recombinant vaccines and the development of new vaccines strategies. Braz J Med Biol. 2012;45(12):1102-1111.