What we currently know about vaccine safety in the veterinary industry, and a look at some of the technological advances that tackle the issue.

Heightened awareness about vaccine efficacy and safety issues, along with the hesitancy created by vocal “anti-vaxxers”, have escalated thanks to SARS-CoV-2 and the COVID-19 disease it causes. A subset of the global population still believes that cats and dogs can become infected with SARS-CoV-2 coronavirus mutants and/or can transmit it to others. While vaccines are not innocuous products, recent notable advances in technology offer improved efficacy and safety for both human and veterinary medicine. The following
text summarizes the current information and availability of these newer technologies.

THE CORONAVIRUS FAMILY

Coronaviruses belong to a large family of related viruses that can infect and cause diseases of the respiratory and gastrointestinal tracts in all mammals and birds. The human strains were first identified in the 1960s and cause common colds, which can lead to bronchitis
and pneumonia. While these are zoonotic microbes that can jump between species and are transmitted between animals and people, an intermediate host is required, such as the horseshoe bat, pangolin (scaly anteater), dromedary camel, and civet cat. These viruses do
not replicate readily in dogs, pigs, chickens or ducks, but do grow readily in wild, zoo and domestic cats, hamsters, ferrets and mink.

CORONAVIRUSES AND COMPANION ANIMALS

No current evidence has found that companion animals can be infected with SARS-CoV-2, although a few positive cat and dog cases have been identified in households where a person infected with COVID-19 resides. There is no evidence that pet cats and dogs can infect other animals or humans. No vaccines are currently available for the respiratory coronavirus infection of dogs.

VACCINE HESITANCY AMID COVID -19

Worldwide infection of SARS-CoV-2 and its disease, COVID-19, has focused healthcare professionals and society on the need for safe and effective vaccines. Even
with the few reports of clot formation arising from the AstraZenica and Janssen J & J vaccines, investigations by the WHO, CDC and others indicated a very low adverse
reaction rate (about 640 per 11.5 million doses given), which falls well within the expected level of vaccinosis events. In the case of the J & J vaccine, clot formation, when it occurred, was linked to people with a congenital Platelet Factor 4 deficiency or other comorbidities.

The rapid development and mass production of effective mRNA, adenovirus vectored, and novel DNA vaccines against these mutating coronaviruses has been remarkable. Once the percentage of vaccinated people reaches 80% or more, the remaining population should be protected by what is known as “herd health immunity” — a concept which applies to all vaccinated species. Further, achieving herd health protection should eventually control the
development and emergence of newly infective coronavirus variants. However, even some fully vaccinated people can still develop breakthrough COVID-19 infections, albeit usually in a relatively mild and self-limiting form.

Novel vaccines to address the recent Omicron SARS-CoV-2 variant with its 37 mutations of the spike protein should be available this spring. The estimated duration of protection from the current SARS vaccines is about five to seven months, with boosters recommended for adults and especially those over 65 years of age.

Vaccinating dogs with commercial enteric canine coronavirus vaccines cannot provide cross-protection against SARS- CoV-2 and the COVID-19 human disease, as the enteric and respiratory canine coronaviruses are different.

BACKGROUND ON VACCINE SAFETY ISSUES

Over 50 years ago, Professor Ron Schultz and I were among the few people cautioning against over-vaccinating pets. We were called irresponsible in public because others were unwilling to consider the idea that vaccines might not always be needed or safe. Since then, an understanding of the efficacy and safety issues pertaining to vaccines has become
more widespread. Please remember that there really is no such thing as “up to date” or “due” vaccinations. Even today, only about 40% of veterinarians are estimated as following the current WSAVA (World Small Animal Veterinary Association), AVMA (American Veterinary Medical Association), AAHA (American Animal Hospital Association), CVMA (Canadian Veterinary Medical Association) and BVA (British Veterinary Association) vaccine policy guidelines.

While modern vaccine technology has clearly afforded effective protection of companion animals against serious infectious diseases, this advancement brings increased risk of adverse reactions (vaccinosis). Enlightened veterinarians can now offer separated vaccine components, rather than give them all together, since the published data show more adverse reactions when multiple vaccines are administered at the same time.

Millions of people, pets and livestock are vaccinated annually, and documented adverse events are relatively rare, estimated at about three to five events per 100 vaccines given. They occur in animals and people that are genetically predisposed, and can be acute, sub-acute, and delayed for up to 30 to 45 days. New data links these reactions to the integrity and function of the gut microbiome. A few reactions are serious, chronically debilitating, and can even be fatal, so we need to balance the benefit: risk equation. As Dr. Schultz has stated, “Be wise and immunize, but immunize wisely!”

CURRENT AND NEW APPROACHES TO VACCINE SAFETY

Vaccine adjuvants

These compounds act to accelerate, prolong, or enhance antigen-specific immune responses. They are added into vaccines to enhance their immunogenicity, but they also
increase the risk of autoimmune and inflammatory adverse events following vaccination. In fact, killed inactivated vaccines containing adjuvants make up about 15% of the veterinary biologicals used, but have been associated with 85% of post-vaccination reactions. On the other hand, while adjuvants have been used safely in human and veterinary medicine for decades, there is increasing worldwide concern about the safety of incorporating thimerosal (mercury) and aluminum salts into vaccines for humans, pets and livestock. The adverse reactions that cause Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) produce polygenic autoimmunity, especially of the connective tissue, following human papillomavirus and influenza virus vaccinations.

More on heavy metals and vaccinosis

Aluminum and mercury salts have been found in the brains of autistic persons, and in vaccine adjuvants that cross the blood-brain barrier after injection, and then persist life-long. There is an urgent need to remove these heavy metals from neonatal and infant vaccines, as these young individuals receive about 17 times more aluminum from vaccines than allowed if doses were adjusted for body weight. Experts now urge that aluminum and mercury not be given in vaccines until after brain maturation (i.e. six to seven months of age, but preferably 12 months). Safer alternatives are available and include calcium phosphate and zinc.

Non-adjuvanted vaccines

PureVax (cats) and RecombitTek (dogs) vaccines are non-adjuvanted, although to date there is no licensed non-adjuvanted canine rabies vaccine. Importantly, leptospirosis vaccines are the second most likely to cause adverse hypersensitivity reactions after rabies vaccines; the brand listed above has the only non-adjuvanted canine leptospirosis vaccine.

Half-dose vaccine products

Studies published in the early to mid-2000s showed that, for both cats and dogs, vaccine reactions occurred more often in small animals and when multivalent combination vaccine
antigens were given together. This author studied small breed adult dogs weighing less than 12 pounds, between the ages of three and nine years, with the pet caregivers’ informed consent. The dogs were healthy, had received no vaccines for at least three years, and were given a half-dose of a two-way canine distemper virus (CDV) and canine parvovirus (CPV) vaccine. Serum antibody titers were measured at one and six months
later and compared to pre-vaccine levels. Results showed that the half-dose vaccine provided sustained protective serum antibody titers for all dogs studied.

The ultra-hybrid FVRCP cat vaccine

This ultra-hybrid vaccine for cats contains the three-way FVRCP (Feline Rhinotracheitis-Calici-Panleukopenia), which is a combination of modified live and killed virus products. It contains two feline calicivirus strains and induces a cross-neutralizing antibody response against multiple FCV isolates obtained from diverse locales across the US. It can be given to kittens eight weeks of age or older, although the duration of immunity has not been determined.

Subunit vaccines

Subunit vaccines contain a purified antigen (proteins, polysaccharides or peptides) instead of whole viruses or bacteria. While intuitively this could be safer, as the components only contain recombinant proteins or synthetic peptides, they can actually be less effective. Subunit vaccines usually do not induce side effects at injection sites and are useful for those with a compromised immune system.

The disadvantages of subunit vaccines involve their reduced immunogenicity compared to live attenuated or killed inactivated vaccines. They typically require adjuvants to
improve immunogenicity, and multiple booster doses are often needed to provide long-term immunity. As these subunit antigens do not infect the cells, the immune response may only be antibody-mediated, and not cell-mediated, to create long-term immune memory. Also, it can be difficult to isolate the specific antigen(s) that will elicit the necessary immune response. Further, a subunit vaccine may lack the pathogen-associated molecular patterns common to a class of pathogen. These associated molecular structures are used by immune cells for danger recognition, and without them, the immune response is less functional.

Kennel cough and canine influenza vaccines

Oral and intranasal Bordetella vaccines release interferon, which impairs the growth of other respiratory viruses (parainfluenza, adenovirus-2, influenza), whereas an injectable
Bordetella vaccine does not release interferon. Intranasal vaccines can cause hypersensitivity reactions, so the newer oral versions are safer and easier to use. But the kennel cough vaccines are not 100% effective. Similarly, canine influenza vaccines (against the highly contagious H3N2 and H3N8 strains) may not be needed as these viruses typically produce short-lived mild clinical signs, like fever and cough. However, when canine influenza is present in dogs harboring Streptococcus spp. in their lungs, 2% to 3% can become seriously infected and die.

VACCINATION, EXPOSURE, AND PROTECTION

CDV (canine distemper virus) vaccinates are immediately protected, if exposed simultaneously to the native virus. MLV CDV does not shed appreciably, but despite the safety moratorium on including the highly infectious Rockborn strain of CDV in today’s MLV vaccines, some still contain traces of it to induce a stronger immune response.

CPV (canine parvovirus) vaccinates are protected from natural exposure after 48 to 72 hours, and so exposed pups can get sick during that interim. MLV CPV sheds from vaccinated dogs three to 14 days post-vaccine, which provides an exposure risk to the unvaccinated or immune-compromised. Shed vaccine CPV is not seen on the Idexx SNAP test, but is present for two weeks on the fecal CPV PCR test, potentially leading to a misdiagnosis of native CPV infection.

The latest advances and technologies outlined in this article have gone a long way toward improving vaccine safety while maintaining adequate protection against infectious diseases.

References:

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Res2(2), 74-77.

Dodds, WJ, Herman, K (2019). Heavy metals in vaccines. J Am Hol Vet Med Assoc 57:
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Dodds, WJ. (2018) Vaccine issues and the World Small Animal Veterinary Association
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Dodds, WJ. (2016) Rabies virus protection issues and therapy. Glob Vaccines Immunol
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Dodds, WJ. Larson, LJ, Christine, KL, Schultz, RD. (2020) Duration of immunity
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Ivanovski I, Ivanovski A, Nikolić D, Ivanovski P. (2019) Aluminum in brain tissue in
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Watad A, Bragazzi NL, McGonagle D, Adawi M, et al. (2019). Autoimmune/
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