Vaccines--Duration of Immunity Challenge Study

When a vaccine is tested to find out whether it prevents the disease it's supposed to prevent, vaccinated dogs are exposed to the organism that they've been vaccinated against. If they've been vaccinated against parvo, they're exposed to parvovirus. This is called a challenge study, because the vaccinated dogs are challenged with the virus.

Not only can you find out whether the vaccine is protective, but you can also expose the dogs to the organism year after year, to find out how long the vaccine is protective. How long a vaccine is protective is called its duration of immunity.

As might be imagined, it's quite costly to vaccinate a group of dogs as puppies and then to maintain them under controlled conditions for years to conduct a duration of immunity study using regular challenges. Because of the expense, very few of these types of studies have been conducted.

Within recent years, there has been some controversy over vaccine schedules, especially concerning whether annual boosters are necessary. Although we know that annual boosters are an excellent way to protect against diseases like parvovirus, distemper, and canine hepatitis, some concerns have been raised about adverse effects of vaccines.

The American Veterinary Medical Association (AVMA) and the American Animal Hospital Association (AAHA) both looked at the types and frequency of vaccinations that dogs are currently receiving. The AAHA recommended that after the puppy series of vaccinations, dogs be boostered every 3 years, instead of every year. This recommendation was made in the absence of published evidence that commonly used vaccines are protective for 3 years.

Just this past year, however, at least 2 studies have been reported that have looked at duration of immunity by challenging vaccinated dogs, and the above study is one of them. Both have been funded by vaccine manufacturers. In the first study, 5 dogs were vaccinated, and in this study, 10 dogs were vaccinated. The vaccine in the first study was licensed for 3-year use (see First 3-Year Canine Adult Vaccine Approved), and the claim made by the above group is that their vaccine is protective for at least 4 years.

Although I have reservations about each of the studies, the point of this post is to alert people who are following this subject that these duration of immunity by challenge studies are finally being conducted and reported.

I suspect anti-vaxers cobbled together a bunch of BS and slapped Dodds' name on it. I don't know of any vet schools that are routinely recommending not vaccinating; that's pure rubbish. Various incarnations of that e-mail and similar have been circulating for years.

From what I can gather, Dodds may have proposed a protocol for immunocompromised pets that advocates titering before revaccinating (not that *that* approach has decent supporting evidence). I don't believe that she advocates not vaccinating, period.

It's a bit difficult to get a fix on her various protocols through the internet, because I don't readily find them on her site (Hemopet). Many of the other sites where protocols attributed to her are posted have credibility issues. This might represent her original protocol, and this might represent her modified protocol for at-risk dogs.

[ December 13, 2004, 06:18 PM: Message edited by: Betsy Iole ]

Posted with Dr. Dodds' permission.

CANINE VACCINATION PROTOCOL – 2004

MINIMAL VACCINE USE

W. Jean Dodds, DVM
HEMOPET
938 Stanford Street
Santa Monica, CA 90403
310-828-4804; Fax 310-828-8251
e-mail: [email protected]


Note: The following vaccine protocol is offered for those dogs where minimal vaccinations are advisable or desirable. The schedule is one I recommend and should not interpreted to mean that other protocols recommended by a veterinarian would be less satisfactory. It's a matter of professional judgment and choice.

Age of Pups & Vaccine Type

9 - 10 weeks Distemper + Parvovirus, MLV (e.g. Intervet
Progard Puppy DPV)

14 weeks Same as above

16 -18 weeks (optional) Same as above

20 weeks or older, if allowable by law Rabies

1 year Distemper + Parvovirus, MLV

1 year Rabies, killed 3-year product (give 3-4 weeks apart from distemper/parvovirus booster)


Perform vaccine antibody titers for distemper and parvovirus annually thereafter. Vaccinate for rabies virus according to the law, except where circumstances indicate that a written waiver needs to be obtained from the primary care veterinarian. In that case, a rabies antibody titer can also be performed to accompany the waiver request.

Posted with Dr. Dodds' permission.
ADVERSE VACCINE REACTIONS

W. Jean Dodds, DVM
Hemopet/Hemolife
938 Stanford Street
Santa Monica, CA 90403
310-828-4804; Fax 310-828-8251


Viral disease and recent vaccination with single or combination modified live-virus (MLV) vaccines, especially those containing distemper virus, adenovirus 1 or 2, and parvovirus are increasingly recognized contributors to immune-mediated blood disease, bone marrow failure, and organ dysfunction. 1-11 Potent adjuvanted killed vaccines like those for rabies virus also can trigger immediate and delayed (vaccinosis) adverse vaccine reactions.7-10 Genetic predisposition to these disorders in humans has been linked to the leucocyte antigen D-related gene locus of the major histocompatibility complex, and is likely to have parallel associations in domestic animals. 5, 7

Beyond immediate hypersensitivity reactions, other acute events tend to occur 24-72 hours afterwards, or 7-45 days later in a delayed type immunological response. 1-4, 6-10 Even more delayed adverse effects include mortality from high-titered measles vaccine in infants, canine distemper antibodies in joint diseases of dogs, and feline injection-site fibrosarcomas. 5,7 The increasing antigenic load presented to the host individual by modified-live virus (MLV) vaccines during the period of viremia is presumed to be responsible for the immunological challenge that can result in a delayed hypersensitivity reaction. 2, 3, 6, 7

The clinical signs associated with vaccine reactions typically include fever, stiffness, sore joints and abdominal tenderness, susceptibility to infections, neurological disorders and encephalitis, collapse with autoagglutinated red blood cells and icterus (autoimmune hemolytic anemia) (AIHA), or generalized petechiae and ecchymotic hemorrhages (immune-mediated thrombocytopenia)(ITP).1, 2, 4, 7, 8, 12, 13 Hepatic enzymes may be markedly elevated, and liver or kidney failure may occur by itself or accompany bone marrow suppression. Furthermore, MLV vaccination has been associated with the development of transient seizures in puppies and adult dogs of breeds or cross-breeds susceptible to immune-mediated diseases especially those involving hematologic or endocrine tissues (e.g. AIHA, ITP, autoimmune thyroiditis). 1,7,10 Post-vaccinal polyneuropathy is a recognized entity associated occasionally with the use of distemper, parvovirus, rabies and presumably other vaccines. 2, 3, 7 This can result in various clinical signs including muscular atrophy, inhibition or interruption of neuronal control of tissue and organ function, muscular excitation, incoordination and weakness, as well as seizures. 7 Certain breeds or families of dogs appear to be more susceptible to adverse vaccine reactions, particularly post-vaccinal seizures, high fevers, and painful episodes of hypertrophic osteodystrophy (HOD).7, 9 Therefore, we have the responsibility to advise companion animal breeders and caregivers of the potential for genetically susceptible littermates and relatives to be at increased risk for similar adverse vaccine reactions.1, 4, 6-9, 14-17 In popular (or rare) inbred and linebred animals, the breed in general can be at increased risk as illustrated in the examples below.

Commercial vaccines can on rare occasion be contaminated with other adventitious viral agents, 3, 15 which can produce significant untoward effects such as occurred when a commercial canine parvovirus vaccine was contaminated by blue tongue virus. It produced abortion and death when given to pregnant dogs,15 and was linked causally to the ill-advised but all too common practice of vaccinating pregnant animals. The potential for side-effects such as promotion of chronic disease states in male and non-pregnant female dogs receiving this lot of vaccine remains in question, although there have been anecdotal reports of reduced stamina and renal dysfunction in performance sled dogs. 17 Recently, a vaccine manufacturer had to recall all biologic products containing a distemper component, because they were associated with a higher than expected rate of central nervous system postvaccinal reactions 1-2 weeks following administration. 17 Vaccination of pet and research dogs with polyvalent vaccines containing rabies virus or rabies vaccine alone was recently shown to induce production of antithyroglobulin autoantibodies, a provocative and important finding with implications for the subsequent development of hypothyroidism. 10

Other issues arise from overvaccination, as the increased cost in time and dollars spent needs to be considered, despite the well-intentioned solicitation of clients to encourage annual booster vaccinations so that pets also can receive a wellness examination.6 Giving annual boosters when they are not necessary has the client paying for a service which is likely to be of little benefit to the pet’s existing level of protection against these infectious diseases. It also increases the risk of adverse reactions from the repeated exposure to foreign substances.

Polyvalent MLV vaccines which multiply in the host elicit a stronger antigenic challenge to the animal and should mount a more effective and sustained immune response. 2, 3, 6 However, this can overwhelm the immunocompromised or even a healthy host that has ongoing exposure to other environmental stimuli as well as a genetic predisposition that promotes adverse response to viral challenge. 1, 2, 7, 14, 16, 17 The recently weaned young puppy or kitten being placed in a new environment may be at particular risk. Furthermore, while the frequency of vaccinations is usually spaced 2-3 weeks apart, some veterinarians have advocated vaccination once a week in stressful situations, a practice makes little sense scientifically or medically.6

An augmented immune response to vaccination is seen in dogs with pre-existing inhalant allergies (atopy) to pollens. 7 Furthermore, the increasing current problems with allergic and immunological diseases has been linked to the introduction of MLV vaccines more than 20 years ago. 3 While other environmental factors no doubt have a contributing role, the introduction of these vaccine antigens and their environmental shedding may provide the final insult that exceeds the immunological tolerance threshold of some individuals in the pet population. The accumulated evidence indicates that vaccination protocols should no longer be considered as a “one size fits all” program. 9

For these special cases, appropriate alternatives to current vaccine practices include: measuring serum antibody titers; avoidance of unnecessary vaccines or overvaccinating; caution in vaccinating sick or febrile individuals; and tailoring a specific minimal vaccination protocol for dogs of breeds or families known to be at increased risk for adverse reactions.6,7,18-21 Considerations include starting the vaccination series later, such as at nine or ten weeks of age when the immune system is more able to handle antigenic challenge; alerting the caregiver to pay particular attention to the puppy’s behavior and overall health after the second or subsequent boosters; and avoiding revaccination of individuals already experiencing a significant adverse event. Littermates of affected puppies should be closely monitored after receiving additional vaccines in a puppy series, as they too are at higher risk.


References

1. Dodds WJ. Immune-mediated diseases of the blood. Adv Vet Sci Comp Med 1983; 27:163-196.
2. Phillips TR, Jensen JL, Rubino MJ, Yang WC, Schultz RD. Effects on vaccines on the canine immune system. Can J Vet Res 1989; 53: 154-160.
3. Tizard I. Risks associated with use of live vaccines. J Am Vet Med Assoc 1990; 196:1851-1858.
4. Duval D, Giger U. Vaccine-associated immune-mediated hemolytic anemia in the dog. J Vet Int Med 1996;10: 290-295.
5. Cohen AD, Shoenfeld Y. Vaccine-induced autoimmunity. J Autoimmunity 1996; 9: 699-703.
6. Schultz R. Current and future canine and feline vaccination programs. Vet Med 1998; 93:233-254.
7. Dodds WJ. More bumps on the vaccine road. Adv Vet Med 1999; 41: 715-732.
8. HogenEsch H, Azcona-Olivera J, Scott-Moncrieff C, Snyder PW, Glickman LT. Vaccine-induced autoimmunity in the dog. Adv Vet Med 1999; 41:733-744.
9. Dodds WJ. Vaccination protocols for dogs predisposed to vaccine reactions. J Am An Hosp Assoc 2001; 38: 1-4.
10. Scott-Moncrieff JC, Azcona-Olivera J, Glickman NW, Glickman LT, HogenEsch H. Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs. J Am Vet Med Assoc 2002; 221: 515-521.
11. Paul MA (chair) et al. Report of the AAHA Canine Vaccine Task Force: 2003 canine vaccine guidelines, recommendations, and supporting literature. AAHA, April 2003, 28 pp.
12. May C, Hammill J, Bennett, D. Chinese shar pei fever syndrome: A preliminary report. Vet Rec 1992;131: 586-587.
13. Scott-Moncrieff JC, Snyder PW, Glickman LT, Davis EL, Felsburg PJ. Systemic necrotizing vasculitis in nine young beagles. J Am Vet Med Assoc 1992; 201: 1553-1558.
14. Dodds WJ. Estimating disease prevalence with health surveys and genetic screening. Adv Vet Sci Comp Med 1995; 39: 29-96.
15. Wilbur LA, Evermann JF, Levings RL, Stoll LR, Starling DE, Spillers CA, Gustafson GA, McKeirnan AJ. Abortion and death in pregnant bitches associated with a canine vaccine contaminated with blue tongue virus. J Am Vet Med Assoc 1994; 204:1762-1765.
16. Day MJ, Penhale WJ. Immune-mediated disease in the old English sheepdog. Res Vet Sci 1992; 53: 87-92.
17. Dougherty SA, Center SA. Juvenile onset polyarthritis in Akitas. J Am Vet Med Assoc 1991; 198: 849-855.
18. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus antibody titers for determining revaccination strategies in healthy dogs. J Am Vet Med Assoc 2000; 217:1021-1024.
19. Flemming DD, Scott JF. The informed consent doctrine: what veterinarians should tell their clients. OJ Am Vet Med Assoc 224: 1436-1439, 2004.
20. Klingborg DJ, Hustead DR, Curry-Galvin E, et al. AVMA Council on Biologic and Therapeutic Agents’ report on cat and dog vaccines. J Am Vet Med Assoc 221: 1401-1407, 2002.
21. Schultz RD, Ford RB, Olsen J, Scott F. Titer testing and vaccination: a new look at traditional practices. Vet Med, 97: 1-13, 2002 (insert).

Posted with Dr. Dodds' permission

CHANGING VACCINE PROTOCOLS

W. Jean Dodds, DVM
938 Stanford Street
Santa Monica, CA 90403
(310) 828-4804; FAX (310) 828-8251


The challenge to produce effective and safe vaccines for the prevalent infectious diseases of humans and animals has become increasingly difficult. In veterinary medicine, evidence implicating vaccines in triggering immune-mediated and other chronic disorders (vaccinosis) is compelling. While some of these problems have been traced to contaminated or poorly attenuated batches of vaccine that revert to virulence, others apparently reflect the host=s genetic predisposition to react adversely upon receiving the single (monovalent) or multiple antigen “combo” (polyvalent) products given routinely to animals. Animals of certain susceptible breeds or families appear to be at increased risk for severe and lingering adverse reactions to vaccines.
The onset of adverse reactions to conventional vaccinations (or other inciting drugs, chemicals, or infectious agents) can be an immediate hypersensitivity or anaphylactic reaction, or can occur acutely (24-48 hours afterwards), or later on (10-45 days) in a delayed type immune response often caused by immune-complex formation. Typical signs of adverse immune reactions include fever, stiffness, sore joints and abdominal tenderness, susceptibility to infections, central and peripheral nervous system disorders or inflammation, collapse with autoagglutinated red blood cells and jaundice, or generalized pinpoint hemorrhages or bruises. Liver enzymes may be markedly elevated, and liver or kidney failure may accompany bone marrow suppression. Furthermore, recent vaccination of genetically susceptible breeds has been associated with transient seizures in puppies and adult dogs, as well as a variety of autoimmune diseases including those affecting the blood, endocrine organs, joints, skin and mucosa, central nervous system, eyes, muscles, liver, kidneys, and bowel. It is postulated that an underlying genetic predisposition to these conditions places other littermates and close relatives at increased risk. Vaccination of pet and research dogs with polyvalent vaccines containing rabies virus or rabies vaccine alone was recently shown to induce production of antithyroglobulin autoantibodies, a provocative and important finding with implications for the subsequent development of hypothyroidism (Scott-Moncrieff et al, 2002).
Vaccination also can overwhelm the immunocompromised or even healthy host that is repeatedly challenged with other environmental stimuli and is genetically predisposed to react adversely upon viral exposure. The recently weaned young puppy or kitten entering a new environment is at greater risk here, as its relatively immature immune system can be temporarily or more permanently harmed. Consequences in later life may be the increased susceptibility to chronic debilitating diseases.
As combination vaccines contain antigens other than those of the clinically important infectious disease agents, some may be unnecessary; and their use may increase the risk of adverse reactions. With the exception of a recently introduced mutivalent Leptospira spp. vaccine, the other leptospirosis vaccines afford little protection against the clinically important fields strains of leptospirosis, and the antibodies they elicit typically last only a few months. Other vaccines, such as for Lyme disease, may not be needed, because the disease is limited to certain geographical areas. Annual revaccination for rabies is required by some states even though there are USDA licensed rabies vaccine with a 3-year duration. Thus, the overall risk-benefit ratio of using certain vaccines or multiple antigen vaccines given simultaneously and repeatedly should be reexamined. It must be recognized, however, that we have the luxury of asking such questions today only because the risk of disease has been effectively reduced by the widespread use of vaccination programs.
Given this troublesome situation, what are the experts saying about these issues? In 1995, a landmark review commentary focused the attention of the veterinary profession on the advisability of current vaccine practices. Are we overvaccinating companion animals, and if so, what is the appropriate periodicity of booster vaccines ? Discussion of this provocative topic has generally lead to other questions about the duration of immunity conferred by the currently licensed vaccine components.
In response to questions posed in the first part of this article, veterinary vaccinologists have recommended new protocols for dogs and cats. These include: 1) giving the puppy or kitten vaccine series followed by a booster at one year of age; 2) administering further boosters in a combination vaccine every three years or as split components alternating every other year until; 3) the pet reaches geriatric age, at which time booster vaccination is likely to be unnecessary and may be unadvisable for those with aging or immunologic disorders. In the intervening years between booster vaccinations, and in the case of geriatric pets, circulating humoral immunity can be evaluated by measuring serum vaccine antibody titers as an indication of the presence of Aimmune [email protected] Titers do not distinguish between immunity generated by vaccination and/or exposure to the disease, although the magnitude of immunity produced just by vaccination is usually lower (see Tables).
Except where vaccination is required by law, all animals, but especially those dogs or close relatives that previously experienced an adverse reaction to vaccination can have serum antibody titers measured annually instead of revaccination. If adequate titers are found, the animal should not need revaccination until some future date. Rechecking antibody titers can be performed annually, thereafter, or can be offered as an alternative to pet owners who prefer not to follow the conventional practice of annual boosters. Reliable serologic vaccine titering is available from several university and commercial laboratories and the cost is reasonable (Twark and Dodds, 2000; Lappin et al, 2002; Paul et al, 2003; Moore and Glickman, 2004).
Relatively little has been published about the duration of immunity following vaccination, although new data are beginning to appear for both dogs and cats.
Our recent study (Twark and Dodds, 2000), evaluated 1441 dogs for CPV antibody titer and 1379 dogs for CDV antibody titer. Of these, 95.1 % were judged to have adequate CPV titers, and nearly all (97.6 %) had adequate CDV titers. Vaccine histories were available for 444 dogs (CPV) and 433 dogs (CDV). Only 43 dogs had been vaccinated within the previous year, with the majority of dogs (268 or 60%) having received a booster vaccination 1-2 years beforehand. On the basis of our data, we concluded that annual revaccination is unnecessary. Similar findings and conclusions have been published recently for dogs in New Zealand (Kyle et al, 2002), and cats (Scott and Geissinger, 1999; Lappin et al, 2002). Comprehensive studies of the duration of serologic response to five viral vaccine antigens in dogs and three viral vaccine antigens in cats were recently published by researchers at Pfizer Animal Health ( Mouzin et al, 2004).
When an adequate immune memory has already been established, there is little reason to introduce unnecessary antigen, adjuvant, and preservatives by administering booster vaccines. By titering annually, one can assess whether a given animal=s humoral immune response has fallen below levels of adequate immune memory. In that event, an appropriate vaccine booster can be administered.
References
Dodds WJ. More bumps on the vaccine road. Adv Vet Med 41:715-732, 1999.
Dodds WJ. Vaccination protocols for dogs predisposed to vaccine reactions. J Am An Hosp Assoc 38: 1-4, 2001.
Hogenesch H, Azcona-Olivera J, Scott-Moncreiff C, et al. Vaccine-induced autoimmunity in the dog. Adv Vet Med 41: 733-744, 1999.
Hustead DR, Carpenter T, Sawyer DC, et al. Vaccination issues of concern to practitioners. J Am Vet Med Assoc 214: 1000-1002, 1999.
Kyle AHM, Squires RA, Davies PR. Serologic status and response to vaccination against canine distemper (CDV) and canine parvovirus (CPV) of dogs vaccinated at different intervals. J Sm An Pract, June 2002.
Lappin MR, Andrews J, Simpson D, et al. Use of serologic tests to predict resistance to feline herpesvirus 1, feline calicivirus, and feline parvovirus infection in cats. J Am Vet Med Assoc 220: 38-42, 2002.
McGaw DL, Thompson M, Tate, D, et al. Serum distemper virus and parvovirus antibody titers among dogs brought to a veterinary hospital for revaccination. J Am Vet Med Assoc 213: 72-75, 1998.
Moore GE, Glickman LT. A perspective on vaccine guidelines and titer tests for dogs. J Am Vet Med Assoc 224: 200-203. 2004.
Mouzin DE, Lorenzen M J, Haworth, et al. Duration of serologic response to five viral antigens in dogs. J Am Vet Med Assoc 224: 55-60, 2004.
Mouzin DE, Lorenzen M J, Haworth, et al. Duration of serologic response to three viral antigens in cats. J Am Vet Med Assoc 224: 61-66, 2004.
Paul MA. Credibility in the face of controversy. Am An Hosp Assoc Trends Magazine XIV(2):19-21, 1998.
Paul MA (chair) et al. Report of the AAHA Canine Vaccine Task Force: 2003 canine vaccine guidelines, recommendations, and supporting literature. AAHA, April 2003, 28 pp.

Schultz RD. Current and future canine and feline vaccination programs. Vet Med 93:233-254, 1998.
Schultz RD, Ford RB, Olsen J, Scott F. Titer testing and vaccination: a new look at traditional practices. Vet Med, 97: 1-13, 2002 (insert).
Scott FW, Geissinger CM. Long-term immunity in cats vaccinated with an inactivated trivalent vaccine. Am J Vet Res 60: 652-658, 1999.
Scott-Moncrieff JC, Azcona-Olivera J, Glickman NW, et al. Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs. J Am Vet Med Assoc 221: 515-521, 2002.
Smith CA. Are we vaccinating too much? J Am Vet Med Assoc 207:421-425, 1995.
Tizard I, Ni Y. Use of serologic testing to assess immune status of companion animals. J Am Vet Med Assoc 213: 54-60, 1998.
Twark L, Dodds WJ. Clinical application of serum parvovirus and distemper virus antibody titers for determining revaccination strategies in healthy dogs. J Am Vet Med Assoc 217:1021-1024, 2000.
Table 1. “Core” Vaccines *
Dog Cat
Distemper Feline Parvovirus
Adenovirus Herpesvirus
Parvovirus Calicivirus
Rabies Rabies
_______________________________________
* Vaccines that every dog and cat should have


Table 2. Adverse Reaction Risks for Vaccines *

“There is less risk associated with taking a blood sample
for a titer test than giving an unnecessary vaccination.”
_______________________________________________
* Veterinary Medicine, February, 2002.


Table 3. Titer Testing and Vaccination *

“While difficult to prove, risks associated with overvaccination
are an increasing concern among veterinarians. These experts
say antibody titer testing may prove to be a valuable tool in
determining your patients’ vaccination needs.”
_____________________________________________________
* Veterinary Medicine, February, 2002.


Table 4. Vaccine Titer Testing *

“Research shows that once an animal’s titer stabilizes,
it is likely to remain constant for many years.”
_____________________________________________
* Veterinary Medicine, February, 2002.