Efficacy of a Half-dose Canine Parvovirus and Distemper Vaccine in Small Adult Dogs: a Pilot Study

Small adult dogs between 3 and 9 years of age, participated in a clinical research study to determine whether giving them just a half-dose of a bivalent canine distemper and parvovirus vaccine (DPV) generated a protective serum antibody titer response 1 and 6 months later in comparison to pre-vaccination titer levels. None of these dogs had received a vaccination for at least 3 years, and all were healthy. The half-dose vaccine generated increased serum vaccine antibody titers for all of the dogs studied. Results varied quantitatively when titers measured on the undiluted serum were compared to endpoint titers determined on the same samples when the serum was serially diluted. The median titer and endpoint titer levels had a sustained increase in all dogs at 6 months post-vaccination. Results confi that receiving a half-dose of bivalent DPV was effi for this study cohort. Further investigations could address a larger number of smaller breed canines. INTRODUCTION Background: ​Vaccination has been and remains the single most important reason why most pet owners bring their pets to veterinarians for an annual or more often “wellness visit” (1–8). Despite evidence indicating that annual vaccinations are not necessary for previously immunized pets, many practitioners are reluctant to change their current vaccination programs. This is likely because they rarely are taught applied clinical immunology and may not understand the principles of vaccinal immunity (that portion of immunity conveyed by vaccines) (1–3, 9). Clearly, the accumulated evidence indicates that vaccination protocols should no longer be considered as a “one size fi all” program (10). Based upon nearly 5 decades of clinical and research experience with vaccinations in companion animals, we have accumulated the following information: the dose of canine distemper virus (CDV) and canine parvovirus (CPV) vaccines can be reduced to 50%, but not more, for small breed and small mixed breed type dogs, based on body weight, and still convey full duration of immunity (1–4). This applies to puppies and older dogs of small breeds and breed types that weigh 12 pounds or less as adults. Serum vaccine antibody titers have also been performed 3 or more weeks 12 ​AHVMA Journal ​• ​Volume 41 Winter 2015 after vaccination. As reported for dogs given a full dose of vaccine (11), greater than 95% of the dogs given a full or a half half dose mounted what is considered to be protective antibody titers to both CDV and CPV (1). To the author’s knowledge, there are no parallel published data on half-dose vaccines given to cats (12–14). It makes little immunological sense to vaccinate toyand giant-breed puppies and adult dogs, to exemplify the 2 size extremes, with the same dose of vaccine. These products are stated to provide a sufficient excess of antigen for the average-sized animal so they are likely to be either too much for the toy breeds or too little for the giant breeds (2). Although the minimum immunizing doses have been established (2, 5–7), the optimum dosages required for disease protection have yet to be determined. Researchers are still uncertain as to whether these dosages should be based on body mass (2, 6). It apparently depends to some extent upon whether the vaccine is of modified live virus (MLV) attenuated origin or killed inactivated viral origin because of the differing immunogenic principles involved (2, 5, 6, 9). According to some experts, killed, inactivated vaccines should be adjusted for body mass, and yet even today, rabies vaccine — the most potent of all such vaccines — is required by law to be given at a full dose to dogs of all sizes (2, 3). More field evidence and clinical data are still needed today on this important issue. Similarly, the administration of identical vaccine dosages for animals in all age groups is questionable (2, 3, 6, 13). The combination of certain specific viral antigens such as CDV with canine adenovirus-2 (CAV-2) (for cross-protection against infectious canine hepatitis virus) and/or with CPV has been shown to influence the immune system by reducing lymphocyte numbers and responsiveness (9) and causing thymic depletion (2, 3). What is the potential effect of those findings on vaccine dosage or age of vaccination, given the wide divergence of size among dog breeds? Why has this been largely ignored by the research and clinical veterinary communities 25 years later? In humans, questions of the vaccine dosage necessary to elicit full protection in infants rather than adults have been addressed for hepatitis B vaccine (15). The investigation was made for economic reasons to determine whether the standard dosage could be split and still afford protection for more than one infant (to reduce costs of vaccinating children in socioecomically deprived countries). One fifth of the adult dose of hepatitis B vaccine was found to protect infants vaccinated during the first 6 months of life (15). Tragically, a similar principle was applied to vaccinating children with a 10to 50fold higher titered measles virus vaccine in an attempt to overcome maternal immunity. Increased infant mortality resulted, especially in girls, who succumbed to other infections because their immune systems became suppressed (2). In one study, adult household pets having adequate to very good serum antibody titers to one or more of CDV, CPV and CAV-2 were given an additional polyvalent booster vaccination (7). Two months later, serum antibody titers to these 3 viruses were measured again. Whereas titers to CDV and CAV-2 showed a signifi increase, those for CPV did not (7), raising the question of whether these dogs were already well-immunized against CPV, or if some other immunological mechanism was being invoked. Regardless, the existing CPV antibody titers indicated that they all should remain protected against street CPV (5, 11). Another study by these same Japanese investigators (6) assessed data from 3 different CDV, CPV, and CAV-2 vaccines that either included or did not include a killed, inactivated leptospirosis bacterin. The purpose of the study was to see if the simultaneous administration of leptospirosis vaccination had any infl upon the serum antibody titers elicited 11– 13 months later. Additionally, this multivariant study examined 3 different adult age and body weight groups. Some confl results were obtained: signifi lower CPV antibody titers were found in dogs vaccinated with leptospirosis versus those not given leptospirosis vaccine for 2 of the vaccines given to the 2-yr old age group and for 1 vaccine given to the 7-yr and greater age group, but no signifi differences were seen at the 3–6 yr-old ages (6). No signifi differences were seen for CPV titers of any group with respect to body weight. For CDV, no differences were seen for any of the age groups, although a signifi lower CDV titer was seen in those receiving leptospirosis vaccines in the medium weight group but for only 1 vaccine product. Results for CAV-2 titers also were lower in the leptospirosis vaccine group but for only 1 vaccine product in the 2-yr age group and also in the small dog size group (6). AHVMA Journal ​ • ​Volume 41 Winter 2015 ​13 What do the results of this complex multivariant study reveal? Solid conclusions are difficult to make, except that adding a leptospirosis bacterin to the polyvalent MLV vaccines reduced the subsequent serum antibody titers primarily against CPV. Does this reduction in antibody titer level leave these dogs susceptible to CPV disease? Probably not, as vaccine protection against the CPV, CDV and CAV-2 “core” vaccine antigens is known to be influenced by the age of the animal, with older animals being less susceptible to these viral diseases (11, 13). However, separating leptospirosis vaccines from the rest of the “core” may be the most reliable way to ensure that adequate “core” vaccine immunity is sustained. Study Objective: ​The purpose of the current study was to document the serum antibody titer responses from administering a half-dose of a bivalent CDV and CPV (a) to small breed adult dogs that had not been vaccinated in at least 3 years. METHODS Eligible small adult dogs betwen 3 and 9 years of age were recruited by posting an announcement on the author’s web site (b) and by e-mail to holistic veterinarians and small breed pet owner clients that are entered into the author’s company electronic Laboratory Information System (c). Participating veterinarians were given an Instruction Sheet ​(Figure 1) ​and Informed Consent Form to be completed at the time of enrollment and signed by the dog owner ​(Figure 2)​. Prior to receiving a half (1/2 dose of the bivalent DPV vaccine (a), a pre-vaccination whole blood sample (3–5 ml) was collected by the participating veterinary clinic and allowed to clot by placing it into a plain red-top glass tube (d). The clotted sample was centrifuged, and the separated serum was decanted and placed into a labeled, empty glass or plastic tube for shipment, by fi class or priority mail in a small padded box, to the author’s laboratory (c). Upon receipt at the laboratory, the serum samples were stored at 4°C until assayed in batches. Serum antibody titers were measured for CDV and CPV using previously established enzyme-linked immunosorbent assay (ELISA) methodology, and optical density (OD) readings were obtained with a spectrophotometer (e) (10). The ELISA assay methods used for CDV and CPV have been shown to have high diagnostic accuracy in comparison to the 14 ​AHVMA Journal ​• ​Volume 41 Winter 2015 reference standard assays of serum neutralization (SN) and hemagglutination inhibition (HI) (16). The participating veterinarians and dog owners had blood from the same dogs collected and processed as described above at 4 weeks and 6 months after each dog had received a half-dose of DPV vaccine. The samples were labeled as 4 weeks Post-DPV and 6 months Post-DPV, and shipped to the author’s laboratory. All 13 samples were assayed at each of the 3 sampling times for CDV and CPV titers; these were measured on the undiluted serum and then in serial dilutions until the endpoint titer was reached. At the 6-month time point, 5 of the samples were inadvertently discarded before being assayed. RESULTS The pilot study enrolled 13 adult dogs that weighed 12 pounds or less and had not received any routine booster vaccines for at least 3 years. Two dogs were rejected because they were over 10 years of age, and another 3 were ineligible as they had received booster vaccinations less than 3 years prior.