What Everyone Needs to Know About Canine Vaccines and Vaccine Programs Presented by Dr Ron Schultz March 5, 2005 Notes taken by Gayle Watkins The three most important things you can give your puppy are: Training Love Vaccines Dr Schultz is not recommending we stop vaccinating puppies. In fact, he says there is no doubt about the importance of vaccines to the health of puppies, kittens and children. This seminar will talk about: (1) Which vaccines should be in a canine vaccination program and (2) How often should they be used? Dr S. began to wonder in the ‘70s why we were vaccinating so much. He saw that we were vaccinating people with only one series of say Measles-Mumps-Rubella vaccine and we never gave another. He also knew distemper (the disease not the vaccine) conferred life-long community so a good vaccine could/should also give life-long immunity. Yet, some diseases provide only short-term immunity, such as cholera. So, we need to know those diseases for which infected animals will be immune for life and those for which animals can be reinfected. The former become the foundation for an effective vaccine program. Vaccines have not changed in over 30 years. Thirty years ago, dogs were vaccinated once in their lives or for the first few years and that was it. Then parvo hit in the late 70s and vets’ views were changed. In response to the epidemic, they went overboard on vaccines. Some even went to weekly vaccines or vaccinated puppies too young. We need to find a balance. So, which diseases confer life-long immunity on dogs that are infected by them? Dogs that get one of these diseases will be immune for the rest of their lives. Distemper Parvo Rabies Adeno Immunity Primer Innate/Non-specific Immunity Acquired/Adaptive/Specific Immunity (90% of protection) - present from birth operates against any substance not enhanced by prior exposure affected by nutrition and age major mechanisms: skin, pH of gut, movement of gut, cilia in respiratory system, mouth secretions, bacteria in gut and on skin probiotics can help with innate immunity (10% or protection) - defense mechanisms tailored to individual pathogens enhanced by prior exposure and vaccines major mechanisms: thymus, bone marrow (primary lymphoid factors) cells move into spleen, lymph nodes, tonsils vaccines can help with acquired immunity Vaccines rarely enhance innate immunity. They are designed to enhance acquired immunity. Women have a stronger immune systems than men. Because of this, they have more autoimmune problems. So, autoimmune problems does not necessarily indicate a weak immune system, it may indicate one that is too strong. Supplements work on the innate system. Stress absolutely diminishes this system, too. Immune-boosting supplements – regulin, dipetptide. Available through vets. Infection is not equal to Disease Many dogs may be infected by a pathogen but few develop clinical disease because their immune systems function well and effectively overcome/kill the pathogen. Thus, infection is much more common than disease. Sterile immunity – animal cannot be infected Other immunity – infection occurs but limited or no disease Neuro-endocrine interaction with the immune system The immune system is not isolated from the rest of the body; all systems work together and effect each other. creating “the best” (i.e., most effective) vaccine causes the strongest reaction in the immune system but it will also trigger the strongest reaction in closely linked physiologic systems endocrine and neurologic are the systems most closely tied to immune system the cells of the immune system are the same as cells in the neurologic and the endocrine system. cytokines = neuropeptides = hormones all of these are the same cells but they effect these three different systems It’s all about balance – every time we stimulate the immune system, we affect something else. Therefore, there can be non-immune changes that arise from vaccines: behavior changes, coat change, hair color, other neurological changes Negative Genetic Responses to Vaccines Ideally vaccines are given to healthy dogs but dogs with minor illnesses can safely be vaccinated. Dogs with immune suppression are a greater problem and such dogs should be vaccinated with caution. There can be negative reactions to vaccines from apparently health dogs. 1. Responders and non-responders. a. The vast majority of dogs are responders—their immune systems can “see” and properly respond to antigens of major diseases. b. Some dogs are genetically predisposed to not respond to vaccines. Nonresponders do not respond to only one agent. Non-responders might not respond to parvo but they will respond to distemper, rabies, etc. c. There immune system doesn’t “see” the antigen. d. Every breed has a small number of non- or low-responders. e. Dobes and Rotties were high in non-responders when parvo hit in 1978. Now there is not a problem in these breeds because the non-responders died. f. Now Labs have more non-responders than other breeds. g. If you have a puppy that does not develop an immune response to two vaccines after 12 weeks of age, he is likely a non-responder. h. Non-responders should not be bred! This is a heritable trait. Only if breeders titer or if there is an outbreak of disease will we know which dogs are non-responders. 2. Adverse reactions, rare but serious. a. Dogs do get injection-site sarcomas but 10 times less than cats. Ferret rates are about the equivalent of cats. b. Seizures 3 days after 1st annual puppy shot is triggered by vaccine. Dogs that seize following vaccines are predisposed but it doesn’t have to be genetic. c. Dr S has no information that any vaccines predispose to mast cell tumors. d. However, strong, inflammatory responses in animals predisposed to cancer can cause neoplasia. Excessive inflammation can trigger cancers, especially in those predisposed. e. We have to keep in mind that the predisposed animal is genetically weak/flawed. f. Weimeraners – breed with the most adverse reactions 3. Auto-immune Problems a. Vaccines can trigger autoimmune disease in all species. This is well known and well established. b. Dr Bob Lewis studied systemic lupus by breeding dogs with SLE. The offspring did not have SLE but they had every other autoimmune disease. The genetic predisposition is for autoimmunity in general not a specific autoimmune disease. He thinks the mode of inheritance for this is polygenic. Vaccine Primer General Risk-Benefit— There is nothing in life that is risk-free. There is risk from vaccines but there is more risk from not vaccinating for these diseases. We must constantly balance the risk and benefit of vaccinating or not vaccinating our dogs. To do so, we must know and weigh: o Risk of dog getting infected o Risk of dog getting disease o Risk of adverse reaction to vaccine o Benefit from vaccine in preventing or decreasing the severity of disease Only use vaccines from major manufacturers – only use vaccines w/one of these labels. Greatest problems from owner vaccinated dogs. o Intervet o Merial Ltd o Pfizer Animal Hospital o Schering-Plough Animal Health o Ft Dodge His colleagues have said they believe over-vaccination is causing immunemediated disease. Vaccines have a higher impact or chance of impact on immune problems than other drugs. Should vaccines be given IM or SubQ? We’ve moved away from IM because it is more painful for dogs even though it is better for the immune system. Don’t switch from sub Q to IM since IM can cause nerve damage and pain. The most dangerous vaccines are bacterial. They act like an adjuvant, driving the immune response in a way that we don’t want to. They are more likely to trigger a generalized immune response. They are: o Bordatella o Lepto o Lyme With puppies, we are balancing a good, robust response that imprints the dog’s immune system with an appropriate response against the threat of disease. Once the immune systems is imprinted, that is how it will respond over the animal’s lifetime. If you screw it up, drive it the wrong way in a naïve animal, you can mess it up for life. Therefore, the most important decisions we make are how we vaccinate our puppies (and children). Combo viruses are fine but not with bacterial product included. Amount of vaccine is not related to size of animal. If you are worried about giving too much vaccine to a small dog, just reconstitute with less solution but use all of the vaccine. Do not split the vaccine between animals. Do not vaccinate pregnant bitches. Ever. Mercury – preservative in human vaccines but not in dogs Vitamin E and selenium deficiency will cause a poor vaccine response. A straight meat diet causes vitamin E/selenium deficiency. The second generation was even easier to put into an E/selenium deficiency so this nutritional effect was passed on genetically. Canine Vaccines Combination vaccines DHLPP – distemper, parvo, parainfluenza, hepatitis/canine adenovirus-1 (CAV1), lepto DHPP (5-way) – no lepto, only the viruses 7-way – 2 lepto serovars plus viruses 9-way – 4 lepto serovars plus viruses Dr S is in favor of combo vaccines: o must be the right combo o w/o bad agents (thus must be viral not bacterial vaccines) o he likes DHPP (distemper-hepatitis-parvo-parainfluenza) Rabies vaccine All non-infectious, killed All adjuvented products, thus has a high risk of adverse reactions Only the rabies vaccine is licensed for a specific period of time. All others are licensed but for no set period of time. So there is no “law” that requires revaccination of any vaccine other than rabies. Lepto vaccines 2-way includes L. canicola* and L. icterohaemorrhagic 4-way includes those two and L. grippotyphosa and L. Pomona * is the most important serovar for dogs. All four can kill dogs and infect humans Bordatella Kennel cough is not a vaccine-preventable disease It is offered alone or with canine parainfluenze (CPI) and CAV-2 Intranasal – always live and in combo w/ parainfluenza and adeno SubQ – no infectious killed Paraenteral Dr S prefers the intranasal. It does not need to be combined with adeno to be effective. If you need an immediate response, the internasal is better. Protects against other viruses. Fewer negative reactions. Dogs will sheds the Bordatella vaccine thru nasal secretions. It is a short-lived vaccine– you’ll be lucky to get 6-9 months of immunity out of it Lyme Vaccine Whole cell, non-infectious killed *OSP-A (recombinant) non-infectious killed Dr Schultz does not recommend using the Lyme disease but, if you do, use the * Giardia Non-infectious, killed Does not recommend Causes a large granuloma Modified Live Vaccine (MLV) or Live Attenuated Vaccine Distemper, parvo, adeno MLVs are the most effective, most efficacious vaccines Because they are more like actual disease than killed vaccines But they are less safe than killed vaccine o So we have to be sensible such as not giving smallpox or MMR to Aids patient o We must be cautious giving MLV to immune suppressed dogs For years, vaccine companies attenuated the agent thus creating the vaccine without understanding how the creation process worked. However, recombinant technology now enables us to understand why the agent is changed and why the change is stable. We are not rid of the diseases covered by MLVs so puppy vaccines are critical. A dog vaccinated as a puppy as lifetime immunity. Combo vaccine – body responds individually but there is some competition for certain cells and it may trigger the release of too much waste. o Bordatella is a hog. It takes over the immune sytem. o Keep bacteria out of viral vaccines. o Multiple virus vaccines have a much calmer response but distemper-parvo alone gives a cleaner response. Might even be better to have them together than individually. Due to maternal immune interference, we must vaccinate once after 12 weeks unless you have titered the puppy to ensure he has had an individual immune response rather than maternal. Titer will tell when individual rather than maternal immunity is present. o At 6 weeks, 50% of puppies will become immune from puppy vaccine o At 9 weeks, 75% will become immune o At 12 weeks, 99% will become immune Sterile immunity to parvo and distemper is 100% effective if the dog responded. You can’t even get them infected. Puppies that react adversely to an MLV vaccine are genetically flawed. They should not be bred. Do recombinant vaccines give long-term immunity? His studies show three-year duration for recombinant. If you have 3-year recombinant vaccine in your dog then he has life-time immunity for the following diseases: distemper, parvo and adeno. Backpassage—return to the actual virus. Distemper vaccine – back passage to the distemper virus in 7 passages but does not shed or return to virulence. Parvo does not back passage. Distemper Distemper vaccine is effective immediately so it can be given at or after exposure and still be effective. Distemper-measles—can be given to puppies as young as 4 weeks if there is an outbreak. Measles is effective against distemper. Can have local and generalized adverse response. Distemper immunity is not age related so dogs MUST be vaccinated. Older dogs are not inherently more immune than puppies. Will a dog get distemper from distemper vaccine? o If you make a puppy immuno-suppressed in the lab, the MLV distemper vaccine will cause distemper o It will cause distemper in the fox, ferret and black-footed ferret without immune suppression o Rockborn strain 1:10,000 puppies will get encephalitis o ______ strain 1:50,000 puppies will get encephalitis (sorry, I didn’t get this word) o But none from either strain will get full blown distemper Puppies vaccinated within the first two weeks of life will get distemper because puppies have no thermoregulatory ability and thus the immune system does not function. You can safely vaccinate the dam because she will not shed the disease from the vaccine. However, distemper is shed in the wild everywhere. Raccoons are “distemper factories.” Unvaccinated dogs with distemper titers got it from wildlife. Merrial has a recombinant distemper vector based on canary pox vector, which causes no disease in the dog so it is the safest vector for canine distemper that leads to an immune response. Recombitech – recombinant distemper Dr S’s made an experimental vaccine made of nucleic acid vaccine for distemper and parvo. Programs animal to produce antigens. The dogs cannot develop hypersensitivity from this vaccine. In a study looking at age-related immunity, nine of the ten vaccinated dogs were fully protected. One was not protected so he developed the disease but he lived. 100% of the unvaccinated adult controls developed the disease with 50% mortality. 100% of the unvaccinated puppy controls developed the disease with 80% mortality. Dogs are at risk for distemper throughout their lives. Parvo 1978 arrival in dogs, swept around the world in 6 months. The virus is very stable and can survive on year in clay and sandy soil. Stable under UV, temp and humidity. Viruses love freezing temps. Don’t use killed parvo! It is coming off the market unless you buy an off-brand, which may continue to be sold. (Do not EVER by off-brand vaccines. Buy only those labeled by the original manufacturer.) All major manufacturers are removing it from the market. Oral vaccines won’t work with parvo. Dogs have strong age-related immunity to parvo. Unvaccinated pups or adult dogs—if a dog makes it to 6 months, parvo is unlikely to kill it since parvo immunity is strongly age related. In a study looking at the age-related immunity, none of the vaccinated dogs were infected. Two of the unvaccinated adult controls developed mild disease and some fecal shedding. All 57 of the unvaccinated puppy controls died. The risk of parvo is primarily during puppyhood. Parvo is shed 3-7 days post vaccination through fecal material, air and oral. Parvo is shed always so be very careful vaccinating dogs in kennel/house if you also have pups less than 2 weeks of age. Parvo causes cardiomyopathy, enteritis and kills young puppies. The benefit of this is that recently vaccinated puppies will shed parvo and revaccinate the adults in household. This happens constantly from wild and vaccine. Cardiomyopathy from parvo. It can happen: o only if you vaccinate an immunologically immune bitch 2 weeks from whelping up to 2 weeks after birth. o shed vaccine in under 2-week old puppies from a naïve dam Adeno defends against hepatits and canine adenovirus 1 and 2 Rabies Rabies vaccine can cause permanent dog-dog (or cat-cat) aggression so don’t do rabies during adolescence. Genetically-engineered MLV rabies is on its way. Does it harm dogs getting rabies every 3 years? Only in the rare dog who dies but for healthy dogs, 3-year rabies do no harm. USDA tests only rabies for minimal duration. Only the product is licensed, not the duration. If you have a dog with an immune disease, rabies can cause insult to its system. If the animal doesn’t need it, don’t give it. Killed or Inactivated Vaccine Lyme, lepto, bordatella, parvo, corona and rabies Jean Dodds—says to use killed but that is far more likely to cause autoimmune reaction/disease. Lyme In dogs, Lyme disease goes to the joints and kidneys. Lyme is an immunopathologic disease. If dogs are diseased, it is the way their body responds to the disease. Lyme is an immune-mediated disease. DOI OSPA 1 year Low efficacy High adverse reactions UWI Vet school does not use Lyme vaccine. Dr S’s recommendation is to treat the dog not the test He recommends C6 reaction test—active infection not vaccinated but 10% of vaccinated dogs will be false negative. Can now do an assay that confirms. IDEX will do a quantitative assay. This vaccine does not provide sterile immunity, it does not defend against infection but may protect against the disease. He doesn’t think he can support the vaccine in the field. Experimental challenge does show some benefit with a oneyear DOI. Two types of Lyme vaccine: 1. The whole cell Lyme vaccine adds other proteins into the body that can cause autoimmune reactions. Lyme is an immune-mediated disease. Whole cell vaccine may trigger generalized immune reaction that may cause kidney disease and other immune-mediated problems. 2. OSP-A neutralizes the Lyme bacteria in the tick so use this one if you vaccinate. Did not find that Lyme crosses the placenta. Frontline and K9 Advantix are probably better defense against Lyme than the vaccine. Western Blot is a good test. Used to validate in office test PCR—polymerase chain reaction Lepto Infection is common but disease is rare. Most infections are sub-clinical. Only 1:3,000 infected dogs become diseased. His vaccine recommendation depends upon geographic area because the lepto vaccine is the most reactogenic vaccine (the one with the highest rate of adverse reactions) 2 puppy shots and annual booster results in no long-term immunity. There is little cross-reactivity between serovars. No one can determine serovar based on serology. Serologic results tell you if dog has lepto but not the infecting serovar. Transmission Direct infected urine venereal crowding bite wounds Indirect contaminated water, soil, food, bedding Freezing and thawing kills bacteria and reduces the disease All mammal species are susceptible to infection with one or more Lepto serovars Primary reservoir bacteria is animals—rats, cattle, beaver Dr. S. can tell the difference between vaccine and infection o Highly endemic 1/100-500 o Endemic 1/1,000-5,000 o Southwest 1/10,000-100,000 DOI from the vaccine is less than 3 months No lepto vaccines should be given before 12 weeks, must have two doses to be effective Give 2-4 weeks apart until15 weeks Boost at 6 months, 1 year and every 6-9 months after Even with that program, efficacy is very bad Cornell’s study (Barr & McDonough) is about to be published that many dogs have no titer after 6 months Corona a vaccine in search of a disease. This vaccine does not show any ability or benefit in the prevention of disease. Giardia This vaccine does not show any ability or benefit in the prevention of disease. Vaccine Protocols New Vaccine Guidelines approved by the American Animal Hospital Association 1. Core – distemper (CDV), parvo (CPV), hepatitis (CAV-2), rabies All dogs should have these four vaccines 2. Optional/non-core – lepto, Lyme, CPI, bordatella, parainfluenza 3. Not recommended – giardia, corona. Not recommended because limited or no disease or mild, self-limiting, easily treated, vaccine has not shown any effectiveness Core Vaccines (CDV, CPV, CAV-2) These diseases are still present in the wild canid population so even if they are reduced in pets, all dogs still need them. AAHA Guidelines o Administer initial puppy series ending at not less than 12 weeks of age. o Boost again 1 year after the puppy vaccine. o Adult revaccination not more than frequently than every three years. Why vaccinate less with core vaccines than we have in the past? o Because the minimum duration of immunity (DOI) for CDV, CPV and CAV-2 is 7-10 years o Because vaccinating more often than every three years adds NO benefit. o Because the risk of adverse reactions, no matter how low, from the administration of a medical product that is not required is an unacceptable medical practice. Vulnerable Period The period during which maternal immunity is down but is still high enough to inhibit immunity from vaccination. Period of vulnerability o 2 weeks with parvo o none with recombinant distemper o < 1 week with regular distemper Dr Schultz’s personal vaccination schedule Vaccinate once and titer. Vaccinate at 8 weeks and titer at 10 weeks His litters – distemper at 6 weeks; parvo at 9 weeks Nothing but Distemper/Parvo for the 1st vaccine then use 5-way combo later at 12 weeks Distemper/Parvo most important and he wants them vaccinated as early as possible while still properly priming their immune systems Rabies – earliest at 12-16 weeks, holding off till 6 months is fine. Optionally, boost 1 year from the vaccine date then every 3 years. o Small percent of dogs do not develop immunity from the first one. o If you don’t have to do the 1 year, then titer instead to ensure the vaccine “took.” o When vaccine is tested during research studies, dogs are not boosted at a year. o Safest protocol may be priming with one vaccine and then 3-4 weeks later doing a second rabies vaccine. Recommendation 1. 6-8 weeks 2. 9-11 weeks 3. 12-14 weeks 4. titer 2 weeks later to verify immunity Do not vaccinate before 6 weeks. In an outbreak, you can go to 5 weeks for parvo. Titer instead. In a real crisis, you can use recombinant distemper at 2 weeks. Nomograph can tell when exactly to vaccinate. Nomographs Nomographs – tells when the puppies should be vaccinated, when maternal antibodies fall low enough for vaccines to work. Cornell used to do but Schultz can do. Cost is $70. Puppies that have not been vaccinated are immunologically naïve. The only specific immunity is from the dam. o 5% comes across the placenta o 95% comes from the three days of colostrums. During this 72 hours the immunity from the colostrum becomes systemic in the puppy. However, it is the dam’s immunity. Puppy must start making its own immunity. Passive immunity disappears. ½ of maternal antibodies disappears every 12 days. Nomographs look at the decay of distemper/parvo immunity in the puppy. Take serum 2 weeks before whelping and post-whelping. Bitch concentrates IgAA in milk at 9 days before whelping so draw serum before then. Bitch distemper/parvo titer 640 320 160 80 40 20 10 5 Birth 12 days 24 days 36 days 48 days 60 days 72 days 84 days Titer has to be below 8-10 to immunize. Little variance among puppies in a litter if they all got colostrum although size has some impact. Smaller pups catabolize faster than larger pups. Serological Testing or Antibody Titers Disease CDV CPV CAV Lepto Rabies Parainfluenza Giardia Lyme Virus neutralization at titer level (sterile immunity) ≥ 80 ≥ 80 ≥ 50 ≥ 100 ≥ 50 No titer correlation although the presence of antibody shows animal has some immune memory Even if titer is low, as long as it is positive, do not give a booster shot. The animal has immunological memory even if it does not have sterile immunity. Before drawing titers, the animal does not need to be fasted. Titer two weeks after vaccine. Boosting a bitch that has a titer, doesn’t work (i.e., it will not increase the immunity she passes on to her pups) unless you are using a recombinant vaccine. If she doesn’t have a titer, boost. If you have sterile immunity, the vaccine can’t replicate so it won’t have any effect. Recombinants can boost. o Parvo will not boost unless titer is < 100. Distemper, only use recombinant. Duration of Immunity Studies Methods Used to Determine DOI for Core Vaccines 1. Challenge—directly challenge the dog with the virulent agent 2. Serology— a. titering shows an excellent relationship between antibodies and protection for the core vaccines. b. This is not the case for all vaccines. For some diseases, titers do not correlate with protective immunity. c. As long as you have any titer, you have immunologic memory. Titers are valid as show by the fact that it is one of the primary methods that vaccine companies use to validate their vaccines. Experimental DOI Studies Study #1 Number of dogs: 19 Breeds/sex: Multiple breeds and sexes Longest period: 11 years from puppy series and 1 year booster Method used to demonstrate protection: serology and challenge Product: A Route of Vaccination: IM Outcomes: 100% survival. All animals were completely protected for life. Vaccine created sterile immunity Study #2 Number of dogs: 82 Breeds/sex: beagles, males Longest period: 9.5 years from puppy series only Method used to demonstrate protection: serology and challenge Route of Vaccination: SubQ Outcomes: 100% survival. None of the dogs were antibody negative. Eight dogs were below the cut-off for sterile immunity but all survived. Study #3 Number of dogs: 37 Breeds/sex: hounds, males and females Longest period: 5 years from puppy series only Method used to demonstrate protection: serology Route of Vaccination: SubQ Outcomes: 100% survival. Study #4 Number of dogs: 7 Breeds/sex: mutiple, males and females Longest period: 14 years from puppy shot at 12 weeks Method used to demonstrate protection: serology Product: D Route of Vaccination: SubQ Outcomes: All dogs have sterile immunity. Study #5 Number of dogs: 79 Breeds/sex: beagles, males Longest period: 9 years from puppy shot Method used to demonstrate protection: serology and challenge Product: B & E Route of Vaccination: SubQ Outcomes: Seven had less than sterile immunity but all were protected. Study #6 ½ dogs vaccinated annually and ½ were given only puppy vaccines and a booster 5 years later. There was no difference with titer or challenge. Manufacturer’s Studies In 2004, manufacturers’ came out w/studies showing 3-4 years duration of immunity (DOI). This confirms Schultz’s results and supports 7-9 years DOI Pfizer – used serological evidence to support DOI (NOTE: i.e., the manufacturers use titers to test their product so we can assume that titers are a good measure of effectiveness.) Schering-Plough – gave guarantee of 3 years Final conclusion: these studies demonstrated that if a dog has four years of immunity, then he has lifetime immunity. Seniors – no need to immunize for Distemper/Parvo since they maintain lifetime immunity from puppy series. Summary Every puppy/dog needs: o At least one dose after 12 weeks of CPV, CDV, CAV o Rabies after 12 weeks Optimal protocol– after 12 weeks for most robust response BUT if they are at risk and susceptible then vaccinate. Designing a Safe and Effective Vaccination Program for your Dog Given by Dr Ronald Schultz August 12, 2001 Notes taken by Gayle Watkins Dr Schultz’s background was in infectious diseases. He was at Cornell but now at U of WI. The Immune System 1) Innate (non-specific) immunity – passive things that help protect dog a) Defenses that include i) Barriers ii) Secretions iii) Chemicals iv) Motility v) Bacterial Competition b) Innate defenses include i) skin—pH, desiccation ii) acid in gut iii) microbial flora iv) GI track (peristalsis, vomiting) v) alveolar macrophages, lung cells vi) lysozyme in secretions in mouth vii) spermine in sperm (bactericidal) viii) cilia (lining of trachea) ix) cough reflex c) All are non-specific d) They keep things out of the body e) Innate immunity protects against 90% of potential hazards f) Hygiene, good health, good nutrition, reduced stress all contribute to innate immunity g) Antibiotic treatments are an assault on this system i) Lactobacillus/probiotics might help restore the flora, does help some and doesn’t really hurt 2) Specific Immunity (Adaptive) – present primarily in mammals a) The higher an animal is in the food chain, the more sophisticated its immune system is. b) There is an intimate relationship between the body’s systems i) Immune = endocrine = neurologic systems ii) Vaccines are drugs (biologics not pharmacologic) and they can affect more systems than any other drug! c) Different set of organs/cells than the non-specific immune system i) Tonsils ii) Maxillary lymph nodes iii) Spleen iv) Thymus (key) v) Bone marrow vi) Mesenteric lymph nodes vii) Bronchial lymph nodes d) Thymus (cell-mediated immunity) and bone marrow (stem cells give rise to antibodies) e) Peripheral lymphoid organs – lymph nodes, tonsils, spleen f) Stem cells fetal liver thymus T cells (internal) antigens/macrophages bone marrow B cells (external) humeral immunity antibodies g) Antibodies prevent infection. All other cells combat an infection. h) Memory cells – key to long-term protection. They are the key to the duration of immunity (DOI). i) The immune system can also cause disease rather than prevent. Immune mechanisms go out of control. Autoimmune—lack of regulation of cell immune reaction. j) Immune problems are pervasive: 50% of human population has hay fever. The same percent of dogs have skin reactions/allergies. 3) Age-related Resistance to Disease a) Innate immunity strengthens with age i) Birth to 6 weeks – changes. For the 1st couple of weeks, puppies are very susceptible because of lack of thermal regulation (39 degrees Centigrade). The immune system is present but it must have an optimal temperature to work. ii) Maternal antibodies are passively acquired through colostrum. Only 5% of a puppy’s immunity comes from the placenta. Colostrum is absorbed in the first 72 hours of life across the gut wall. (1) So with orphans, you have three days to get colostrum into them. (2) It’s better not to tube feed them. (3) Make colostrum out of 1 part milk replacer and 1 part serum (or plasma) from the dam or adults in the same household or as close to home as possible (to give them antibodies against local threats) (4) Feed this for 3 days! At least one of three daily feedings. (5) Beyond three days, use plasma instead of serum and inoculate subQ, interperitoneally or intravenously. The puppy’s gut has stopped absorbing and now it digests anti-immunoglobulin. The dam also passes cytokine cells but those can’t really be passed through the gut wall. (6) If nothing is done, the pup will have increased risk of early death. It will need a protected environment. (a) w/artificial colostrum – 10% chance of dead puppy (b) w/o artificial colostrum – 90% chance of dead puppy iii) When to vaccinate puppies (1) Never vaccinate pups < 2 weeks of age. Without passive immunity, the vaccine will cause disease. Earliest to vaccinate an orphan is 4 weeks w/ only distemper. The safest distemper is recombinant vectored vaccine (Recombetek by Merriel). (2) Vaccinating earlier than 4 weeks, you are compromising the puppy’s immune system. (3) Ideal – 9 weeks is earliest; 12-15 weeks is ideal (4) Vaccinating at 6 weeks hits them at their lowest immune point because of the stress of weaning so do it later. (5) Peak of the immune system is at 6 months, then it plateaus between 7-9 months and stays steady until 9 years. (6) All canine diseases except rabies exhibit age-related immune changes. Older dogs are much more immune than puppies, except for rabies which hasn’t been studied. Older dogs over 12 and cats over 15 do not need vaccines. iv) Diseases differ in the effect that age has on immunity (1) Canine Parvovirus (CPV) – strong age-related contingent (a) Puppies infected w/ parvo at 16 weeks have a 50% mortality (b) Puppies infected w/ parvo at 1 year have a 10% mortality (2) Feline leukemia – vaccinated at 9-12 weeks and again at 1 year. Never vaccinate again because age-related responses are stronger than any vaccine can confer. Vaccine Thoughts 1) General a) Every puppy in the world should receive distemper and parvo. b) There is not a puppy in the world who needs a corona vaccine. c) Not a dog in the world that needs a Lyme vaccine, even in CT. d) Natural diet (all meat) can detrimentally affect the immune system. e) Lepto and rabies—have public health implications because diseases are zoonotic (can be passed to humans). Lepto vaccine may be beneficial to dog but it is detrimental to humans because the vaccine does not prevent shedding. Infected dogs will shed lepto and humans can be infected f) Individuals who are sensitized by vaccines are genetically predisposed to this reaction or other autoimmune reaction. g) Never use killed distemper vaccine. h) Efficacy and safety are often inversely related. i) Always buy from a major manufacturer (Pfizer, Scherring-Plough, Intervet, Merriell, Ft Dodge); never by off-brand (such as Century, Foster and Smith) j) Non-responder dogs that cannot respond to vaccines should not be bred! Breeding will continue the problem. k) Self-antigen—induced autoimmune reaction in response to vaccine. Those who are genetically prone to autoimmune disease will get sick. l) Nosode—study for the AVHolistic MA showed no immunizing potential. 2) Killed vaccines – pathogen is inactivated and adjuvant added to vaccine to enhance reaction. a) General b) c) d) e) f) g) h) i) j) k) i) Lepto, bordatella, Lyme are killed ii) Distemper and adeno should not be killed Pros i) No reversion to virulence ii) Safer for dogs who are immuno-compromised or pregnant iii) Undetectable contamination at time of manufacturing is rendered nonpathogenic Cons i) More frequent adverse reactions ii) 2 doses are required iii) Expensive iv) Adjuvant needed. Adjuvant non-specifically stimulates the immune system. v) Killed vaccines have higher rates of vaccinosis because of adjuvant, which stimulates the immune system to self and to antigens. FeLV (killed) caused adverse events in 50% of cats. To control the disease, test and isolate from < l year old kittens rather than vaccinate. Dr S. does not like combo vaccines that include killed vaccinations. 5-in-1 vaccines don’t have a killed component and thus do not have any adjuvant. Subunit vaccines – antigens are separated from whole organism purified into vaccine. Requires adjuvant. Bordatella systemic (not intranasal) – very powerful adjuvant/non-specific. Nasal is less likely to cause adverse reactions. Dr S has challenge date that shows rabies is good for up to 9 years. He could make a 7-year rabies vaccine. Pfizer distemper-measles is the best vaccine in high-risk distemper situations. Can do as early as 4 weeks in an outbreak. Lyme is immune-mediated disease so it can be caused by the vaccine. They use recombinant. Common infection but uncommon disease. The disease is highly treatable and often mild in the dog. 1-3% react to vaccine. The vaccine does not protect from infection or reinfection. Do not vaccinate a naïve individual before 6 months of age. Dr S. likes bordatella/parainfluenza intranasally. System bordatella drives system to hypersensitivity, especially IGA. Dr. S. recommends not more than one time per year. Kennel cough is an environmental disease not immune. Deal with ventilation and stress rather than vaccinate. It is not a vaccine-preventable disease. Non-core vaccine. He never vaccinates for bordatella but boarding can cause it because the environment contributes. Find another kennel! When animals die from KC, something else has caused it. Killed product (such as lepto) - #1 shot sensitizes the system and the #2 shot immunizes. This is true except for rabies since only one dose needed. 3) Modified Live Vaccines (MLV) – attenuated. a) General i) MLVs do infect the dog; it is the infection that causes immunity. ii) Reactions are possible and should be recorded and sent to the USDA. AVMA is improving reporting. Pharmocopeia –online reporting. Owners can report. b) Pros c) d) e) f) g) h) i) i) Less frequent adverse reactions ii) Less cost iii) Parental or mucosal administration iv) Interferon release in a few days of vaccination v) Usually stimulates stronger CMI reaction vi) Normally does not contain adjuvant Cons i) Potential for disease ii) Vaccinal virus shed iii) Higher risk for pregnant and immune compromised animals iv) Short shelf life v) Easily inactivated by heat, etc. vi) Undetectable contamination Size is unrelated to the dose of MLV vaccine. It is individual-specific not size. Amt must be more than the minimum. Rehydrate with less solution rather than reducing the dose of the vaccine. Parvo sheds but distemper does not. Shed parvo does not cause disease. Distemper vaccine 1:10.000 caused encephalitis. With MLV, depends upon the host’s immune response. Individuals with immune compromised may not develop immunity and may develop disease. Vector vaccine – vaccine created w/i an antivirulant vector. i) Purevax – cat rabies, MLV-vectored vaccine so no adjuvant and no firbrosarcoma. Only a 1-year rabies. For bacterial toxins, such as tetnus, memory cells don’t help provide long-term immunity. 4) Vaccinating Dogs a) Vaccinating pups who already have sterile immunity (complete immunity; dogs with sterile immunity cannot be infected) from earlier vaccination with MLV vaccines will not cause any problems; the MLV vaccine will be neutralized. BUT vaccinating dogs with sterile immunity with a killed vaccine can cause severe problems. b) Both of these are okay for puppies i) 2-way for puppies (Distemper-parvo) ii) 5-way for puppies (Distemper-parvo-adeno-parainfluenza) c) Basic principles of a vaccination program i) Vaccinate ≠ immunize ii) Immunize requires some sort of an immune response iii) Goals – expand clones of T & B cells, and develop memory cells (remember antigen for up to the life of the animal) iv) Titer – tells you if there is still immunologic memory (1) Parvo – 1:40 has a memory response that protects from disease. 1:100 and above, do nothing. Less than 100, revaccinate. (2) Titer 2 weeks after the final puppy vaccine. Never run another unless dog has become immune compromised. (3) Cornell is the only lab that he recommends. Every commercial lab uses other tests that haven’t been studied under challenge. He hasn’t seen the supporting documents for Jean Dodds’ titers. v) Never revaccinate a brood bitch, particularly one when she is pregnant or in season. vi) The program (1) 6-8 weeks – Distemper-parvo (2-way) (2) 9-12 weeks – 5-way (DHPP) (3) 12-14 weeks – Rabies (now or later) and a 5-way. If you are going to do non-core start them now at the earliest (4) 12-15 weeks – for lepto . Don’t give Lyme in October. Feb-April makes more sense. vii) What does he do with his own dogs? Vaccinates once and titers 5) Major Issues in Vaccine Program a) Earliest age, 6-9 weeks, exceptional 3-5 weeks, never < 2 weeks b) Necessary vaccines and type c) Efficacy of current vaccines d) Risks of current vaccines e) How often to revaccinate f) Should titers be preformed g) Future expectations h) If adult dogs are immunized, puppies in show homes are not at greater risk. He would not be afraid to take an unvaccinated dog to shows where all dogs are vaccinated. 6) Core: Distemper, parvo, adeno, rabies a) Necessary Vaccines i) Canine Adenovirus (CAV) ii) Canine Distemper (CDV) iii) Canine Parvovirus 2 (CPV-2) iv) Rabies Virus (RV) b) Series i) Separate rabies from other vaccines since it is the most reactogenic. If you separate it, you know it is the rabies that caused the reaction. When there are no other antigens in competition. Give rabies IM and 5-way sub Q. ii) If last puppy shot is given 12-14 weeks, there will be no interference w/ maternal antibodies. iii) Normal 6 weeks – 9 weeks – 12 weeks – 15 weeks iv) Ideal puppy series 9 weeks – 12 weeks -15 weeks v) Make sure there are 2-4 weeks between puppy shots. Weekly vaccines cause hypersensitivity and poor immune response. vi) Getting an immune response to the first encounter is critical to the proper development of the pup’s immune sytem. vii) Lepto. Don’t do lepto before 12 weeks. Normal 15 weeks 2 shots, 2-4 weeks apart. Ideal 16 weeks works best. Titers are useless w/ lepto. Lepto is zoonotic so we can get it from dogs shedding w/ no clinical signs. 7) Non-core vaccines (only for high-risk dogs) a) The non-core vacciensare i) Parainfluenza (CPI) but if you give this in a 5-way, it isn’t a problem ii) Lepto – causes many adverse reactions iii) Lyme iv) Bordatella v) Corona (CCV) —he hasn’t met a dog that needs this vi) Giardia—he hasn’t met a dog that needs this. Same as lepto in that shedding can continue so do not use it. b) Pre-administration of benedryl reduces hypersensitivity doesn’t suppress immune system like steroids will. 8) Efficacy – excellent for core vaccines, good to very good for CPI and bordatella, poor for lepto 9) Vaccine Interference: a) Corona interferes with lepto b) Corona interferes with adeno and parvo c) Lepto interferes with Lyme 10) Duration of immunity -- Minimum duration of immunity (DOI) a) CDV min 5 years, max 7 yrs b) CAV min 7, max 9 yrs c) CPV min 7 11) Make sure there are 3 days between major stressors. Give the vaccine first so the body has time to respond before next stressor. 12) Reactions a) Minor ≤ 1 in 100 doses b) Major ≤ 1 in 5,000 doses 13) Nutrition a) Trace minerals and vitamins – immune system is very sensitive to deficiencies i) Zinc, Vit E, Selenium – don’t overdo selenium. He talked about 400 IU of E. ii) Bitch’s milk runs out of many nutrients b) A good diet during pregnancy and weaning is critical immunologically. c) Vit E deficiency causes increase in homolyzing of erythrocytes d) Too much antioxidants may trigger autoimmune diseases because it strengthens the immune response 14) Autoimmune Problems a) Autoimmune problems trigger between 2 and 6 years in dogs b) Dogs and humans have the highest rates i) Diabetes ii) Lupus iii) Hemolytic anemia c) Genetic component is very strong for autoimmune disease d) Lepto, Lyme and bordatella vaccines can affect reproductive health.