IN order to decide the most effective time to vaccinate a foal we must firstly consider our current knowledge on the ontogeny of the foal’s immune system and the differences in its response to disease and vaccination.
The foal is born with the components of the immune system in place but it is immunologically naive and due to the epitheliochorial structure of the placenta is dependent on passivelyderived colostral immunity for specific antibody. The range of colostrally derived antibodies is dependent on the vaccination status of the mare and the range of antigens to which she has mounted an antibody response.
In order to provide effective protection against disease, vaccines should stimulate a response that mimics protective response to natural infection. We need to understand how the horse mounts a protective immune response to natural challenge by the particular organism in order to evaluate the efficacy of the vaccine in providing protection to the individual.
The immune system
Innate immune response
The innate immune system provides the body’s first line of unconditional defence. The response is immediate and non-specific so requires no previous exposure to the organism. It has no memory and is dependent on the immune system recognising the invading organism as non-host via broadly specific receptors that recognise pathogen associated molecular patterns.
The cell surface receptors in macrophages and dendritic cells are called Toll like Receptors (TLR). Cytokines are released in response to antigen binding at these sites. This results in inflammation at the site and can also trigger cell mediated and antibody mediated adaptive immune response. The innate system also produces antimicrobial peptides in response to pathogen invasion and recognition. Complement is involved in the innate response.
Adaptive immune response
This part of the immune system is targeted against specific organisms and requires previous exposure. The adaptive response involves B and T lymphocyte interactions following specific antigen recognition. The response is slow, taking 3-5 days for clones of cells to develop. Antibody response takes 10-14 days after primary exposure. Response is magnified by repeated exposure.
What is different about the newborn foal’s immune system?
Although all the components of the immune system are present in the newborn foal, the efficacy of the system is reduced when compared to the adult. Different components mature at different rates. Lymphocyte numbers are reduced, B-lymphocytes are only present at a third of adult levels and increase over the first few months. Cytotoxic lymphocyte response to organisms such as R.equi are not effective in three-weekold foals and does not become effective in all foals until about eight weeks. Neutrophils have reduced phagocytic ability that is enhanced by absorption of adequate quantities of colostrum.
Complement is present at 13% adult levels at birth, decreased levels of cytotoxic lymphocytes for the first 6-8 weeks. Young foals exhibit decreased expression of interferon gamma for the first few months.
Foals are able to produce antibody soon after birth; however, the type of antibody response is age dependent with IgGb only being detected after 63 days.
The importance of colostrum
Colostrum is produced under hormonal control during the last 2-3 weeks of pregnancy as a unique event. It involves selective transport of IgG to the mammary gland. Colostrum contains Blymphocytes, cytokines, complement, hormones and growth factors that enhance the foal’s innate immune system.
There is considerable individual variation in the quality and quantity of colostrum produced by individual mares. The concentration of total IgG does not reflect individual specific antibody levels (see Figure 1).
Colostrally derived antibodies have a relatively short half-life between 20-30 days, depending on the sub-class. Endogenous antibody production rises slowly over the first 5-10 months in response to challenge. This results in a trough in antibody levels between 6-12 weeks of age.
How the foal responds to natural infection
A foal responds to natural infection by a pathogen, for example influenza, at three levels.
- There is local immune response based on secretory IgG and IgA on the respiratory mucosal surface. If this is effective it prevents invasion of the respiratory mucosa.
- However, if the mucosa is breached, cytotoxic T cells in the underlying tissues and lymph nodes provide the next level of defence.
- If these defences fail to halt the invasion, serum antibody is important in neutralising the virus.
When can a foal respond to vaccination?
A foal is able to respond to vaccination soon after birth; however, there are several points to consider when assessing the ability to respond appropriately. It has been shown with particular reference to influenza that even a very low level of colostral antibody can interfere with the foal’s response to vaccination. In one trial, some individuals from well-vaccinated mares did not respond effectively till after seven months of age.
It has been shown that foals do not produce a full range of antibodies in response to challenge. IgGb response takes up 63 days to develop. The balance of the T helper response has a “hangover” from the mare’s recognition of pregnancy.
T helper cell responses
Cytokines are the hormonal messengers of the immune system. They are produced in the main by T cells, in particular CD4 T helper cells. The T helper cells are the major cytokine producers and can be subdivided into Th 1 and Th 2 type responses. The T cells have antigen specific, cell surface receptors.
Th 1 type cytokines tend to have a pro-inflammatory response. Gamma interferon is the major Th 1cytokine, TNF and beta interferon are also secreted. Th 1 type responses are important in intracellular killing. Th 2 cytokines include interleukin -4, 5, 10 and 13. They are also involved in allergic type reactions and IgE. They have an anti-inflammatory response. It is thought that a balance between these two responses produces clearance of the invading organism without disease developing.
T helper response in the foal
Maintenance of pregnancy requires some degree of immunosupression. It is thought that placental factors influence the maternal immune system, down regulating Th 1 response, thought to be important in allograft rejection. This switches the maternal immune system to a Th 2 bias that inevitably has an influence on the foetal and neonatal immune system, favouring Th 2 type responses.
This is supported by evidence that neonatal foals are gamma interferon deficient. We almost exclusively see disease associated with the intracellular pathogens R.equi and Lawsonia intracellularis in foal and weanlings.
Types of vaccine
In order to overcome the differences in the ability of the foal’s immune system to produce a protective response to vaccination, the different types of vaccine should be considered.
Dead vaccines
Although these vaccines are considered safe, as the antigen does not multiply in the foal, a minimum of two doses is required and the adjuvant has a significant influence on the efficacy of the response and the balance between Th 1 and Th 2 response.
Alum tends to produce a Th 2 type biased response; in mice, ISCOMs have been shown to induce a balanced response.
Live vaccines
Live vaccines contain the antigen with attenuated pathogenicity. The organism will multiply in the host stimulating both cell mediated and antibody responses.
The immunity produced tends to be longer lasting. However, live vaccines are not considered safe in immunosuppressed individuals, this would include pregnant mares.
Virus vectored vaccines, in particular the Canary pox influenza vaccine, have been shown to circumvent the inhibitory effect of passively derived maternal antibody in the foal.
DNA vaccines
DNA vaccines contain DNA plasmids that synthesise the antigenic proteins in a way that mimics natural infection. This then stimulates cell mediated and antibody response.
However, this vaccine technology is still evolving and there is as yet no commercially available DNA vaccine for horses although West Nile Fever vaccine has been produced in the US, and the use of an experimental R. equi vaccine has been reported in foals.
When should we vaccinate our foals?
There are several things to consider when making recommendations about the age to start a vaccination programme in foals. These include:
- The ability of the foal’s immune system to mount an adequate response to the vaccine used.
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A significant inhibitory effect of maternally derived antibody on the foal’s response to the vaccine has been shown. In foals from vaccinated mares this inhibitory effect with regards to tetanus and influenza has been shown to persist for at least 26 weeks.
Foals vaccinated at three months failed to increase antibody levels to influenza and tetanus in response to two doses of vaccine, requiring a further 1-3 doses to mount antibody response comparable to those of yearlings given two doses of vaccine.
Antibody levels of the mare and efficacy of transfer of maternally derived immunity will influence degree and persistence of this effect.
As a consequence, foals from correctly vaccinated mares should not commence a primary vaccination course until at least six months of age. Foals from unvaccinated mares should be considered differently and will need protection particularly against tetanus from an earlier age. Commencing the primary course between 3-4 months of age is usually recommended.
- The evidence of risk of infection and timing of that risk should be considered. This will require knowledge of the management of the population being considered.
Usually on stud farms the risk of influenza is very low and the highest risk will be when yearlings go through the sales ring or into training, so producing a response to the primary vaccination course is more important than providing early protection.
Conversely, the risk of tetanus is likely to be significant so protection should be provided earlier; timing is dependent on vaccination status of the mare. It may be worth considering starting vaccination for the tetanus and influenza at different times.
Studies have shown a silent cycle of EHV1 infection in unvaccinated mares and foals; however, once vaccination of mares was instituted EHV1 and EHV4 continued to be identified from nasal swabs of vaccinated mares and their unweaned, unvaccinated foals.
It found evidence of infection in the first five weeks of life, confirming that vaccination of the mares failed to break the continued infection cycle of EHV1 and EHV4. However, vaccination with commercially available vaccines has been shown to reduce the level of virus shedding and incidence of abortion.
Conclusions
- Now you know why you should have paid more attention in immunology classes.
- There is still more we don’t know than we do about the development of the foal’s immune system!
- Remember foals are different.
- Assess individual risks:
- – maternal antibody status
- – location
- – movement
- – population
- Think about type of vaccine. We are in a time of changing vaccine technology and it is important to keep abreast with developments in this field and what is commercially available.
