What Issues You Need to Consider Before You Vaccinate Your Dog or Cat

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From theory to practice

In the previous chapter, you learnt how mammals (including humans and pets) get immunized against a pathogenic microbe.

The primary immune response is the reaction of the adaptive immune system to a first exposure to a pathogen. It is slow and rather weak.

If the individual survives to the first infection, he will be able to react to the subsequent exposure to the same pathogen with the secondary immune response which is strong and quick: he is immunized.

The whole concept of vaccination is to induce a strong primary immune response, without causing sickness to the patient, by exposing the body to the pathogen.

Thus, vaccines contain the whole pathogen (attenuated or inactivated), fragments of it, or only parts of its DNA.

To design vaccines, scientists have to choose from some options:

• Type of vaccine: live, inactivated, recombinant
• Route of administration: injectable, nasal or oral and the injection site (for injectable vaccines)
• Excipients and especially whether an adjuvant is necessary
• The vaccination program that will result from the choices above but also from the outcomes of the clinical trials that will be conducted afterward.

Finally, keep in mind that a vaccine is an industrial product that has to comply with constraining states regulations and that should follow the development steps that guarantee its quality.

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The story starts in the 15^th century in China with a method called variolation. It consisted of inoculating via the nasal mucosa mildly virulent strains of smallpox.

This process was considered as a fairy tale in Europe. Nevertheless, in 1796, the English doctor Jenner decided to test it. He inoculated cowpox to some of his patients (Cowpox is close to smallpox. Cowpox is a serious disease for bovines, but causes only mild symptoms in humans).

Dr Jenner’s patients became then unaffected by any contamination with smallpox. They were “immunized” although the concept didn’t exist at that time.

Dr Jenner called the cowpox Variolae vaccinae. This is the origin of the term “vaccination”.

A century later, Louis Pasteur took the concept to a new level. He theorized the notion of attenuation for live vaccines and created the first vaccines against rabies and anthrax.

First inactivated (killed) vaccines were also designed at the very end of the 19^thcentury, by Pasteur and other teams from the US, Germany and the UK.

By the 1940’s, biologists understood that they could attenuate a virulent strain by making it replicate in cell cultures. Since then, they have been extensively using this method for producing most live vaccines.

The development of vaccine technologies has picked up pace over the last decades, thanks to a better understanding of the immune system. Scientists now seek to produce purified antigens via genetic engineering.

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Live attenuated vaccines

Live vaccines contain live bacteria or viruses whose virulence is dramatically reduced so that the patient can't get sick.

A pathogen's virulence is its ability to multiply within a host and cause damage:

• For a bacterium, it will be its ability to replicate quickly, to adhere to epithelia, to release toxins...
• For a virus, it means its ability to attack its host's cells, to multiply and to disseminate

Until recently, the attenuation was obtained by repeated culture. Nowadays, wild pathogens are genetically modified.

Live vaccines are more effective, because they are... alive. Only live vaccines can reproduce the dynamics of a real infection. They are especially recommended against viruses because they are much better for mobilizing cell-mediated immunity.

Because they are more effective, live vaccines generate a longer duration of immunity and require boosters less often.

However, they are more prone to causing adverse events. The pathogen may sometimes recover a part of its initial virulence within its host. The symptoms are usually mild. But it is therefore not recommended to use live vaccines on immunocompromised patients.

There is another drawback. Cold chain integrity should be maintained from the production until the administration to a patient. This means that live vaccines need to be stored in refrigerators and transported in refrigerated trucks.

Non-live vaccines

This category is made of all the other vaccines.

Because these vaccines are not alive, no replication is possible and the vaccination can't reproduce a real infection. They do not mobilize the immune system as much as a live vaccine does. And especially, cell-mediated immunity is less involved.

Non-live vaccines contain either complete inactivated (killed) pathogens or, fragments of the killed pathogen, or genetically engineered antigens or even toxins produced by the pathogen.

In every non-live vaccine pharmaceutical companies add adjuvants that increase inflammation at the injection site. Thus, the immune response is reinforced and more memory cells are created.

Generally, non-live vaccines need a booster every year. They induce less adverse effects, except at the injection site because of the pro-inflammatory effect of the adjuvants.

Inactivated or killed vaccines

They are made of full viruses (inactivated vaccines) or bacteria (killed vaccines) inactivated by heat or chemicals.

The structure of the pathogen remains intact and therefore presents all its original antigens to the immune system. But still, it can’t replicate a real infection.

Toxoid vaccines

These vaccines are not aimed at controlling the pathogenic germ but at limiting the damage from the toxins it produces.

Toxins are extracted and then purified from the pathogen culture. They are then administered to the patient with some excipients. The immune response consists of the production of antibodies directed against the toxin’s antigens.

Polysaccharide and conjugate vaccines

These vaccines target the antigens of the capsule of encapsulated bacteria as, for instance, Streptococcus. These capsules are mainly made of polysaccharides.

The issue here is that polysaccharides send a weak signal to the immune system. They do not activate T-cells and especially helper T-cells. The overall immune response is weak. Frequent boosters are needed to maintain protection.

A conjugate vaccine is the combination of a polysaccharide vaccine and a protein carrier. The protein carrier is selected for its high immunogenic capability, especially with regards to T-cells.

Compared to polysaccharide vaccines, conjugate vaccines are a big step ahead in term of the strength of the immune response they generate and of the duration of protection.

Recombinant vaccines

Recombinant vaccines involve the selection of one or several antigens from the pathogen.

The gene(s) coding for this(ese) antigen(s) are then inserted into a vector, generally a virus. There are 2 options:

• The vector is injected into the patient
• Or the vector serves as antigens producer and the antigens are injected into the patient.

This is advanced technology. The challenge is to select the antigens that elicit a strong immune response and are very specific to the bacterium/virus they come from.

The recombinant vaccine strategy gives more control on the development and production of the vaccine. It can target several pathogens at a time and induces much less adverse events than attenuated live vaccines.

Although recombinant vaccines can also trigger T-cells immune response, they need strong adjuvants and multiple injections to ensure an adequate level of protection.

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In chapter 1, we've seen that the primary immune response requires the mobilization of Antigen Presenting Cells (APC: macrophages and dendritic cells) which generally patrol not far from the periphery of the body, close to the skin and the epithelia.

It makes sense since it is precisely where pathogens break into the body.

When choosing the route and/or the site of administration, vaccines designers seek to put the antigens in contact with the white cells of the immune system for as long as possible, in order to induce a strong immune response.

This is why vaccines are always administered in the peripheral regions of the organism: close to the skin, to the mucous membranes or in the peripheral muscles. Far away from large blood vessels which would dilute too quickly the antigens the vaccine brought in.

Intramuscular (IM)

This is the most frequent and the easiest way to inject a vaccine. The vaccine is injected in muscular tissues.

Subcutaneous (SC)

The injection site is located just under the skin.

It seems that this type of injection generates more adverse events on the site of injection.

Intradermal (ID)

The injection site is situated in the dermis, the layer of the skin just below the epidermis. Because the skin is thin, the injection needs to be very precise, which makes it a bit difficult.

Oral

This is the easiest route of administration. No needle needed!

Oral vaccines trigger the production of IgA antibodies, known for their protective effect against mucosal infections.

Nasal

Nasal vaccines follow the natural route of respiratory infections. Nasal vaccines elicit both the mucosal and the systemic immune systems.

They are easy to administer to human patients. Not so much to animals.

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Passive immunization is the transmission of active antibodies to a non-immune individual.

Passive immunization occurs when a mother transmits her antibodies to her fetus in the last third of her pregnancy in utero (IgG antibodies), or to her newborn through her milk (IgA antibodies).

This protection is very useful since newborns have a weak immune system and rely almost exclusively on the defenses provided by the mother. For instance, premature newborns have a higher risk of contracting an infection.

Passive immunization is also a therapeutic solution that helps patients in need of an urgent solution: either because of a current infection or an immunodeficiency. They will be injected with serum from an immune donor (human or animal) containing the specific antibodies for the pathogen. This is a short term medical measure.

For example, human patients bitten by an animal suspected to be rabid receive an injection with a serum containing antibodies specialized against rabies virus antigens.

Transmitting cell-mediated immunity would consist of injecting effector T-cells. It is not feasible. It would require closely matched donors (histocompatible).

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Vaccination failure

There are 3 main causes of vaccination failure: maternal antibodies, poor immunogenic vaccine, and poor responding patients.

Maternal antibodies

During pregnancy the mother transmits her antibodies to her fetus in utero. Later on, she keeps on giving some to her newborns via her milk.

These antibodies necessarily interfere with the vaccines administered to her puppy or kitten. Maternal antibodies destroy the vaccines' antigens and neutralize them before the puppy or kitten has got the time to build up its own immunity.

Maternal antibodies gradually disappear from the animal’s blood within a few months.

It would be best to vaccinate just at the moment when nearly all the maternal antibodies have vanished. But the speed at which they disappear varies a lot from a kitten or puppy to another.

The ideal time is therefore impossible to anticipate!

This why most vaccination programs for kittens and puppies recommend 3 injections 2-3 weeks apart and taking place within 6 to 16 weeks of age.

During this large period of time, it is possible to avoid maternal antibodies while giving a good level a protection to younger pets.

Poor vaccine immunogenicity

Vaccines manufacturing standards are high nowadays. Vaccines are a large market for pharmaceutical companies and vaccines are made in large facilities that strictly follow legal manufacturing requirements. In addition, once produced, vaccines are tested.

There may be some issues though. Live attenuated vaccines require to be kept at low temperature. Rarely, there are some unnoticed accidents during storage or transportation that inactivate totally or partially this living material.

Some inactivated/killed vaccines have naturally a poor immunogenicity and sometimes fail to initiate a proper immune response.

Poor animal response

Young and aging pets have a weaker immune system. They may respond poorly to immunization attempts.

A study (Kennedy et al. 2007) showed that smaller breeds have a better and more durable antibody response than larger ones. They should respond better to vaccination.

As immune response is genetically determined, there should be some differences from one breed to another or from one individual to another.

Serological testing

You may find some tests that measure the quantity of antibodies circulating in the blood (or serum) for some pathogens.

It is a way to assess if an animal is still immunized after a vaccination. It tells if the vaccination was successful or if the animal is still immunized. It avoids unnecessary boosters.

It is not perfect, though.

If the test is positive (i.e. there are enough antibodies circulating in the blood), it’s OK. Everything’s fine. The animal is immunized. It is not necessary to administer a booster.

However, a negative test doesn’t mean that the animal is not immunized and because:

• There may still be numerous memory B-cells that can transform very quickly in antibodies releasing plasma cells
• Cell-mediated immunity is not measured with antibodies titers

These tests are more expensive than the vaccination itself. It questions their usefulness.

However, this is good medical practice: it is now recommended by academic experts that you shouldn't vaccinate your pet more than what is strictly necessary.

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How to vaccinate young puppies or kittens

Without the maternal antibodies, a newborn would be vulnerable to many infections.

In the first weeks of life, puppies' and kittens' immune system is far from being mature:

• Effector B-cells take more time to differentiate and proliferate
• Less antibodies and memory cells are produced
• Plasma cells produce short-lived antibodies

It makes vaccinating a puppy or a kitten a bit tricky. On one hand, the immature immune system does not react strongly. On the other hand, the maternal antibodies neutralize a part of the vaccine antigens.

This is why vaccinating a puppy or a kitten requires several injections. It gives the immune system more exposure to the pathogen’s antigens.

Usually, kittens' and puppies' vaccination programs include 3 injections 2-3 weeks apart, starting at 6-8 weeks of age.

How to vaccinate adult dogs or cats

After the initial series of vaccinations as a puppy or a kitten, a dog or a cat should be vaccinated at 1 year of age (sometimes you may be advised to do it at 6 months).

Afterward, dogs or cats should be vaccinated every 3 years with live vaccines.

Non-live vaccines are less effective. Usually a yearly booster is recommended.

Vaccination against rabies is often required by law. You should refer to the regulation in your state or country and stick to it.

How to vaccinate aging dogs or cats

As for all organs, the immune system gradually weakens over time. This deterioration accelerates at the end of life.

There is an overall and marked decrease in the number of all types of lymphocytes. Antibodies are fewer and develop a lower affinity for antigens. The immune system loses part of its reactivity against new infections. Furthermore, it fails to maintain immunization in the long run.

As a result, aging pets become more susceptible to infections and need boosters more often.

The issue is that this preventative measure is often overlooked. Vaccination schedule should be recalled at each geriatrics visit to the vet.

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In a shelter, a kennel or a cattery, infections can spread rapidly. Animals come in frequently. Some of them may have a poor health status or carry infectious diseases.

Shelter managers need to prevent the onset of epidemics in their facilities. They have to ensure that any pet joining the group doesn't carry any serious infective pathogen.

Whenever a new pet enters a shelter, its immunization record is checked. If the vaccination record is not up-to-date, it will get the missing vaccines.

In the case of puppies or kittens the WSAVA recommendations are reinforced due to the higher risk of being infected. Young pets should get their first injection at 4-6 weeks and then every 2 weeks until the age of 20 weeks.

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The duration of immunity is the time span during which a pet is protected by a vaccination.

For many years, owners were advised to vaccinate their pet every year.

Nowadays, experts consider it was a bit too much. It was due to the lack of long lasting clinical trials.

Recent experiments (Schultz 2006) indicate that dogs or cats vaccinated with live vaccines are immunized for at least 3 years.

Inactivated vaccines induce a weaker immune response. In this case, boosters are required on a yearly basis and sometimes more frequently.