A well-developed immune system is essential for healthy pigs. Even a so-called perfect immune system teamed with the “best vaccine” won’t protect all the pigs in the herd. There will always be susceptible pigs.
The key to any good herd vaccination program is when a large enough percentage of the animals develop immunity (usually 70-80%), so that the pathogen cannot spread easily in the herd. This protection is referred to as “herd immunity.” Vaccination results in a “shift to the right” of the non-vaccinated animals, so that most of the pigs (now vaccinated) are protected against the disease.
It is important to understand the essential components of the immune system and management for a proper immune response and good herd immunity.
Physical, chemical and microbial barriers to infection at body surfaces are the first line of defense against disease. These barriers include the epithelial cells of the skin, gastrointestinal, respiratory and reproductive tracts along with bactericidal fatty acids, normal bacterial and fungal flora, the mucous layer and the flow of mucous, low pH, bile and numerous enzymes. Defensins, antimicrobial peptides produced by epithelial cells, also form a chemical barrier to limit infection at epithelial surfaces and attack invading bacteria.
Stress and dehydration can have a large effect on natural immunity by decreasing natural secretions and making the skin and the mucosal linings of the respiratory, digestive and reproductive tracts more prone to infection.
Once microorganisms breech the various barriers, the innate immune system is the first responder to the pathogen invasion. This system consists of white blood cells (neutrophils, eosinophils, monocytes, natural killer [NK] cells and macrophages), complement (a protein that sticks to a number of pathogens to mark them for destruction by the white blood cells), and special immune system hormones called cytokines (interferon, inflammatory mediators) that play a key role in attracting immune cells to the site of infection and make all immune cells grow and mature.
This first responder occurs in two waves. The first wave that occurs in the first few hours features the arrival of neutrophils, non-specific killers of bacteria along with inflammatory cytokines that recruit other white blood cells and activate cells to increase killing and also turn on the adaptive immune response.
Interferon, the last component of this first response, sets up an immediate wall against virus infections. The second wave that occurs a day or two later is the NK cells that kill virally infected cells, but also produce cytokines to help the adaptive immune response.
The innate system looks for different kinds of pathogens using receptors that recognize shared parts of bacteria, fungi and viruses. The neutrophils and macrophages attack and kill many bacteria and fungi, often with the help of complement. The major innate defense against viruses is interferon, which is released by virus-infected cells and causes the infected cell to die and the surrounding cells to be virus-resistant.
Macrophages and NK cells also destroy virally infected cells. A special kind of macrophage called an antigen-presenting cell (APC) ingests the pathogens and breaks them into small pieces called antigens. These cells also produce cytokines that activate cells from the adaptive immune system.
Adjuvants in vaccines help these APC ingest the vaccine organisms and also help produce more cytokines. Adjuvants are chemical and/or biological substances added to vaccines to make them work better. These APC “loaded up” with these specific antigens move to the lymph nodes where they interact with the adaptive immune cells.
Innate and adaptive immunity have a hand and glove relationship. The innate immune response activates the adaptive immune system during swine vaccination or pathogen invasion. Without an innate immune response, there can be no adaptive response. This response doesn’t begin until 3-4 days after vaccination or infection. The pig is born with billions of T and B cells. Each cell has an antigen that it specifically “recognizes.”
However, the number of cells specific for any antigen is small (1 out of 10,000 cells). To get a good adaptive immune response, these T and B cells must recognize the antigen, and then be stimulated to grow multitudes of pathogen-specific cells. The APC cells initially interact with the T cells (Figure 1) and there is a dose effect. The more APC to interact with the T cells, the better the response and “memory” of the response.
The T helper cell is vital to activating this adaptive response, interacting with the APC, and then dividing and producing cytokines to make other T and B cells grow and mature (Figure 2). The adaptive system is specific for each pathogen, enhanced by vaccines and will be “remembered” (memory), so the animal’s resistance to disease will be increased.
There are two types of adaptive immunity: cell-mediated and humoral. Cell-mediated immunity involves immune cells acting directly against pathogen-infected cells. Humoral immunity involves specific immune proteins (antibodies) that are directed against pathogens. This system uses T cells, B cells, cytokines and antibodies to provide this long-term protection.
The T and B cells are specialized white blood cells responsible for adaptive immunity. The T cells provide cell-mediated immunity. They get their name because they develop in the thymus, a specialized immune organ needed for T cell growth. The T cells are divided into two groups — T helper (TH) and T cytotoxic (Tc) cells. The T helper cells’ major job, when they “recognize” or see their specific antigen, is to produce cytokines to help the other T and B cells grow and divide, and to grow and divide themselves to produce more cells to fight future infections.
The T cytotoxic cell (cytotoxic means “cell killer”) is a specialized T cell that is helped to grow and divide by the T helper, but whose job is to destroy pathogen-infected cells. These antigen-specific cells find and destroy infected cells without hurting the cytotoxic T cell, leaving the cytotoxic T cell to kill more infected cells.
The B cells grow and divide with the aid of cytokines from the T helper cell (Figure 2 ). Their job is to produce specific antibodies against pathogens; some are produced and secreted into respiratory, reproductive and digestive tracts, and some are secreted in milk. The antibody on the surface of the respiratory, reproductive and digestive tracts helps protect the pig by sticking to the pathogens even before the animal’s cells get infected. The antibody in the bloodstream will also provide specific protection, even if the animal gets infected.
The mucosal immune system provides the first immune defense barrier for more than 90% of potential pathogens. The gut mucosal immune system alone contains more than a trillion lymphocytes and has a greater concentration of antibodies than other tissues in the body. It protects against harmful pathogens, but also tolerizes (induces tolerance) the immune system to dietary antigens and normal microbial flora.
The mucosal immune system is not well developed in the newborn pig and gradually develops over the first six weeks of life. This system includes not only immune cells, but the epithelial cells of the mucosa that help with antigen recognition and immune modulation. The epithelial cells are coated with a mucous-glycocalyx layer that helps protects the cells, while at the same time the epithelial cells of the mucosa are continually in contact with commensal and pathogenic organisms.
In the mucosal lymphoid tissues, mature T-cells and B-cells that have been stimulated by antigen and induced to switch to produce IgA will leave the submucosal lymphoid tissue and reenter the bloodstream. These lymphocytes will exit the bloodstream and locate near mucosal surfaces. The B cells will differentiate into plasma cells that will secrete IgA. Many of these cells will return to the same mucosal surface from which they originated, but others will be found at different mucosal surfaces throughout the body. This homing of lymphocytes to other mucosal sites throughout the body is referred to as the “common immune system.”
Immunity in the Young Pig
Prior to farrowing, many antibodies are concentrated in the first milk as colostrum to be transferred to the piglet. Immune cells (mainly macrophages and some T cells) are also transferred in colostrum. Because the piglet has an immature immune system, the immunity of 14- to 21-day-old piglets hinges on this passive immunity provided by colostrum.
Passive immunity provides short-term protection for piglets. Length of protection depends on the level of sow antibodies absorbed by the piglet, and how fast the antibodies are broken down in the piglet over time. Half of the antibodies will be gone at 8-16 days of age and totally gone by 30-60 days. Because this rate of disappearance varies by type of antibody and piglet, the length of disease protection from passive antibody can also vary greatly (Figure 3).
There is a window of disease susceptibility when passive immunity wanes and before protective immunity is reached. Passive antibody can actually interfere with this process. This is particularly true in the young pig given a live-virus vaccine, like for porcine reproductive and respiratory syndrome (PRRS) virus. Passive antibodies prevent the virus from growing and inducing active piglet immunity.
Most vaccines administered to young piglets are killed bacterial vaccines that have adjuvants. These killed products have two advantages in stimulating active immunity, even in the presence of passive immunity. First, they don’t have to grow to induce active immunity. Second, the adjuvants aid in the development of active immunity by stimulating the APC, and also by protecting the bacterial antigens from passive antibody.
At weaning, the pig can mount active immune responses. The weaning period is characterized by diet change, low feed intake, poor growth and development, diarrhea and increased risk for disease from enteric pathogens. Unfortunately, the maternal milk factors that control the immune response and provide specific antibody in the piglet are no longer available at weaning and the balance between tolerance and active immunity is disturbed. The magnitude and severity of this weaning crisis at the gut mucosa is dependent on how much the immune system was expanded during the preweaning period.
Unfortunately, the point where the production system determines the weaning age, and when the immune system is ready for weaning don’t coincide, so managing the immune system for optimal disease prevention when weaning early will continue to be a challenge.
Developing the gilt and providing a good activation of the immune system are keys for introduction into the sow herd. The gilt’s immune system develops quickly, responds well to pathogen exposure and vaccination at 3-4 months of age.
Gilts need to be vaccinated against known herd pathogens. Since most vaccines are killed bacterial vaccines, gilts need to receive the proper vaccination regime, including a primary dose, followed a few weeks later with a booster dose for a good, active immune response.
Exposing gilts to cull sows before breeding provides good exposure and development of an active immune response against herd pathogens. Because of their prior vaccination and exposure history, sows can be given boosters semiannually to maintain active immune protection.
Feeding the Immune System
The immune system does not get a free ride when it comes to nutrition. It requires energy, protein, vitamins and trace minerals. Activating the innate and adaptive immune systems is an energy-dependent process. Just as it takes a minimum amount of energy for normal maintenance of the pig’s bodily functions, energy is needed to mount an immune response. A major reason for the development of high-health pig systems is to redirect this energy that the immune system would use for growth and lean deposition.
The goal of early weaning is to remove the piglet from the sow before passive immunity disappears and the pig becomes infected with pathogens from the sow that will activate the immune system and cause disease.
All-in, all-out management lessens pathogen spread between groups. Confinement housing reduces exposure to environmental pathogens.
Conventionally reared pigs weaned at 21-28 days of age and raised in continuous-flow and/or outside lots are exposed to pathogens from the sow, environment and other pigs. These pigs’ immune systems respond to these pathogens, diverting energy from lean growth, and decreasing rate of gain and feed efficiency.
The major driver for immune system activation is to prevent disease that greatly affects economic return caused by death loss, decreased feed efficiency and average daily gain.
Immunosuppression of PRRS and PCV2
Porcine reproductive and respiratory syndrome (PRRS) virus and porcine circovirus type 2 (PCV2) both modulate the immune response. Much of the impact of PRRS and PCV2 on the swine industry is due to their ability to adapt to the immune system’s ability to control other pathogens.
The consequences of PRRS infection are highly dependent on pig age. PRRS virus lasts longer and grows higher in piglets, affecting the innate immune system and, in particular, the macrophage. The resulting PRRS immunosuppression produces more secondary infections in young pigs. Finishers and sows have a much lower level of infection from PRRS virus.
PCV2 also affects the innate immune system, targeting monocytes, macrophages and dendritic cells (DC), which have critical roles in preventing bacterial infections and the development of the adaptive immune response. Unlike PRRS vaccination that has variable efficacy, PCV2 vaccination, whether in the pregnant sow or the young pig, is efficacious in reducing the severity of PCV2-associated diseases.
In planning a swine vaccine program, assess the disease risks at the production sites. Blanket vaccination programs are often suggested for many pathogens that may or may not be a threat. Review the antigens that are being used to make sure they make sense for the operation.
Secondly, consider the effect of maternal immunity and the age of the pig. The relationship is linear — the younger the pig, the poorer the response, and the older the pig, the better the response. However, the inverse relationship is true for protection afforded by maternal immunity — the younger the pig, the better protection due to high levels of maternal antibody, and the older the pig, the more susceptible to disease due to the decreasing maternal antibody.
Minimizing exposure of piglets to pathogens using all-in, all-out systems and good biosecurity can provide enhanced protection and give an extended window before vaccination is necessary. However, in management systems where continuous flow and lower biosecurity are practiced, a more aggressive vaccination program may be warranted.
When should booster vaccinations be given? In all animals following vaccination, there is expansion in the populations of antigen-specific T and B cells. However, to have a complete and mature immune response, this lymphocyte expansion must not only stop, but also an active process of cell death (apoptosis) must occur. This waning process allows culling of T or B cells that may be poor responders or even cause autoimmunity to be removed.
This whole process from vaccination to achieving mature immune response takes at least 17-21 days. The fully developed, mature primary response can then be boosted to get a true anamnestic or secondary response. Often, swine vaccine primary and booster doses are administered at two-week intervals. In young pigs, this is done to provide an opportunity to make sure that the pigs develop a primary response in the face of maternal immunity. The adjuvants that are used with most commercial vaccines provide superior immune development over older generation adjuvants. Therefore, in most instances, if primary vaccination occurs after 3 weeks of age, booster vaccination beyond three weeks and even longer will be efficacious. The dogma that revaccination must occur within two weeks of the primary vaccination is not true, and the anamnestic response will be better with more time.
The use of autogenous vaccines is a common practice in swine medicine, important to control PRRS virus and swine influenza virus (SIV). They were used extensively for PCV2 control before commercial PCV2 vaccines were available. For PRRS virus and SIV, their greatest value has been in differentiating the field strains from commercial vaccine strains. This science-based application of autogenous vaccines is tremendously important for preventive swine health.
But the cost savings from using autogenous vaccines should not be the major factor in selecting an autogenous vaccine over a commercial vaccine. Always let science, not the economic bottom line, guide whether an autogenous vaccine is used.
There are many reasons why vaccinated animals contract disease. Four major reasons for these failures include: 1) vaccine administered in the face of maternal immunity; 2) vaccine administered after infection; 3) improper handling of vaccines and/or administration equipment; and 4) immunosuppression at the time of vaccination.
A major challenge in developing an active immune response in young pigs has been interference from maternal immunity. Vaccine timing administrated by the parenteral route (not through the digestive tract) involves estimating when the level of maternal antibody is low enough for an active immune response to progress sufficiently to provide vaccine immunity.
Maternal antibody half-life in pigs is 11 to 20 days. The prime window for vaccination can be anywhere from a few weeks to three months, varying by animal and the level of maternal antibody and the vaccine antigen. (Figure 4 on page 19). This presents a major challenge to getting an adequate vaccine response. Antibody levels often decay to a level still high enough to block responses to vaccine, but not high enough to resist a field infection; this creates a window of opportunity for infecting organisms.
The host requires several days after vaccination before an effective immune response will develop. If the animal encounters an infectious agent prior to or near the time of vaccination, the vaccine may not have time to induce immunity. The animal may come down with clinical disease resulting in an apparent vaccination failure. In this situation, disease symptoms will appear shortly after vaccination and may be mistakenly attributed to vaccine virus. Modified-live vaccine viruses consisting of attenuated virus may be capable of producing disease in immunosuppressed animals.
Improperly handled and administered vaccines may fail to induce the expected immune response in normal, healthy animals. Modified- live bacterial and viral vaccines are only effective if the agent in the vaccine is viable and able to replicate in the vaccinated animal.
Observing proper storage conditions and methods of administration are very important for maintaining vaccine viability. Failure to store the vaccine at refrigerator temperatures or exposure to light may inactivate the vaccine. Even when stored under appropriate conditions, the vaccine loses viability over time. Therefore, vaccines that are past their expiration dates should not be used. The use of chemical disinfectants on syringes and needles can inactivate modified-live vaccines if there is any residual disinfectant. The use of an improper diluent or the mixing of vaccines in a single syringe may also inactivate modified- live vaccines. Vaccines should not be mixed with other vaccines to create a single vaccine for injection.
Immunosuppression due to a variety of factors, including stress, malnutrition, concurrent infection or immaturity, may also lead to vaccination failure. If immunosuppression occurs at the time of vaccination, the vaccine may fail to induce an adequate immune response. If the immunosuppression occurs sometime after vaccination, then disease may occur due to reduced immunity in spite of an adequate response to the original vaccine.
Vaccines are not Cure-Alls
Vaccines aren’t a substitute for management, proper nutrition, adequate facilities or biosecurity. Vaccine programs are designed to provide herd immunity, not individual pig immunity. Maintaining a healthy pig means having a healthy immune system. Overcrowding animals and inducing stress will disable the immune system. The immune system needs energy and is highly susceptible to poor nutrition, including vitamin and mineral
Increasing pathogen loads by continuous-flow systems and poor cleaning and maintenance will overwhelm the ability of the immune system to protect against pathogens. Increased pig densities have allowed pathogens like PRRS and PCV2 to flourish. Our ability to fine-tune and enhance the pig’s immune system and increase animal productivity will only improve over time with proper management.