Canine Vaccine Research Articles

2022 AAHA Canine Vaccination Guidelines (2024 Update).

Vaccination is a cornerstone of canine preventive healthcare and one of the most cost-effective ways of maintaining a dog's health, longevity, and quality of life. Canine vaccination also serves a public health function by forming a barrier against several zoonotic diseases affecting dogs and humans. Canine vaccines are broadly categorized as containing core and noncore immunizing antigens, with administration recommendations based on assessment of individual patient risk factors. The guidelines include a comprehensive table listing canine core and noncore vaccines and a recommended vaccination and revaccination schedule for each vaccine. The guidelines explain the relevance of different vaccine formulations, including those containing modified-live virus, inactivated, and recombinant immunizing agents. Factors that potentially affect vaccine efficacy are addressed, including the patient's prevaccination immune status and vaccine duration of immunity. Because animal shelters are one of the most challenging environments for prevention and control of infectious diseases, the guidelines also provide recommendations for vaccination of dogs presented at or housed in animal shelters, including the appropriate response to an infectious disease outbreak in the shelter setting. The guidelines explain how practitioners can interpret a patient's serological status, including maternally derived antibody titers, as indicators of immune status and suitability for vaccination. Other topics covered include factors associated with postvaccination adverse events, vaccine storage and handling to preserve product efficacy, interpreting product labeling to ensure proper vaccine use, and using client education and healthcare team training to raise awareness of the importance of vaccinations.

Assessing the impact of a potential canine vaccine for the control of Chagas disease: a mathematical modeling study

IntroductionChagas disease, a zoonotic infection transmitted by triatomine bugs, poses serious public health risks in endemic areas. As dogs are important reservoirs in the disease’s spread, developing a canine vaccine could be transformative for controlling disease transmission to dogs and humans.MethodsWe developed a compartmental Susceptible-Infected model to simulate the transmission dynamics of Trypanosoma cruzi, considering interactions among dogs, humans, cats, rodents, and triatomine vectors. We used the model to assess the direct and indirect impacts of two vaccine mechanisms—all-or-nothing and leaky—on disease incidence across different host populations. The sensitivity of the model’s outcomes to changes in input parameters was analyzed using univariate sensitivity analysis.ResultsOur model showed that with a 90% vaccine efficacy, an all-or-nothing vaccine could reduce the cumulative incidence of T. cruzi in dogs by 91.3% over five years. The 60% and 30% vaccine efficacies would result in reductions of 63.47% and 33%, respectively, over 5 years. Similarly, the leaky vaccine achieved a 92.62% reduction in dog infections over 5 years with 90% efficacy. The indirect effects on human T. cruzi infection were notable; the all-or-nothing vaccine reduced human disease incidence by 14.37% at 90% efficacy, while the leaky vaccine achieved a 32.15% reduction over 5 years. Both vaccine mechanisms may substantially reduce T. cruzi incidence among dogs, and generate indirect benefit to other hosts, such as humans, by reducing their infection risk. The indirect benefits of vaccination were heavily influenced by the proportion of triatomine bugs blood meals taken from dogs.DiscussionThe study highlights the potential of targeted canine vaccination in controlling Chagas disease transmission and burden in endemic countries. It provides additional evidence for pursuing the development of a canine vaccine as a valuable tool for Chagas disease elimination.

Conceptual debates in the study of canine & feline vaccine hesitancy: A response to Haeder 2023

Conceptual debates in the study of canine & feline vaccine hesitancy: A response to Haeder 2023

A New Licensed Quadrivalent Antileptospiral Canine Vaccine Prevents Mortality, Clinical Signs, Infection, Bacterial Excretion, Renal Carriage and Renal Lesions Caused by Leptospira Australis Experimental Challenge.

L. Australis is one of the most prevalent Leptospira strains infecting dogs, leading, in natural conditions, to severe life-threatening cases. The objective was to evaluate the onset and duration of immunity (OOI and DOI) induced by a new licensed quadrivalent antileptospiral vaccine (EURICAN® L4) including four Leptospira components (Canicola, Icterohaemorrhagiae, Grippotyphosa and Australis) against L. Australis. To this end, a severe L. Australis challenge model was developed, using a canine strain recently isolated from the field. Seven- to ten-week-old puppies received two doses of the vaccine four weeks apart and were challenged with an L. Australis isolate two weeks (OOI) and 12 months (DOI) later. Mortality, clinical signs, leptospiremia, leptospiruria, renal carriage, and renal lesions were assessed after challenge. The challenge induced multiple severe clinical signs in controls, leading to the death or euthanasia of 83% of puppies and 57% of adults. In controls, leptospiremia was detected in all dogs, leptospiruria in 67% of puppies and 86% of adults, kidneys tested positive for Leptospira in 83% of puppies and 71% of adults, and kidney lesions were observed in 100% of puppies and 86% of adults. In addition, thrombocytopenia associated with increased concentrations of urea, creatinine, and aspartate aminotransferase was recorded in controls displaying severe clinical signs. In both OOI and DOI studies, none of the vaccinates had clinical signs, no Leptospira was detected in blood, urine, and kidney samples, and no kidney lesions were observed in vaccinates. No significant changes in hematological and biochemical parameters in vaccinates were recorded. EURICAN® L4 was shown to induce quick and long-lasting protection against a severe L. Australis infectious challenge, preventing mortality, clinical signs, infection, bacterial excretion, renal lesions, and renal carriage.

Isolation of Virulent Leptospira Serogroup Australis Field Strains from Symptomatic Dogs for Canine Leptospiral Vaccine Development.

Leptospirosis is a widespread zoonosis caused by spirochaetes belonging to the pathogenic species of Leptospira, which are classified into more than 25 serogroups and 250 serovars. Vaccination can prevent the disease in dogs but offers incomplete efficacy because of a lack of cross-protection between serogroups. The aim of this study was to validate a robust recruitment and sampling process, with the objectives of isolating and typing circulating Leptospira pathogenic strains and then selecting those of proven virulence and pathogenicity for vaccine development. Blood and urine samples from dogs with clinical syndromes compatible with acute leptospirosis were sterilely collected and transported to a reference laboratory for a micro-agglutination test (MAT), PCR, and bacterial isolation. Isolated strains underwent molecular typing using RNA16S, variable-number tandem repeat (VNTR), and pulsed-field gel electrophoresis (PFGE). Subtyping was performed using core genome multilocus sequence typing (CgMLST). Among 64 included dogs, 41 had MAT and/or PCR results compatible with Leptospira infection, and 14 Leptospira strains were isolated. Based on molecular typing, 11 isolates were classified as L. interrogans serogroup Australis, serovar Bratislava, and 3 as serogroup Icterohaemorrhagiae, serovar Icterohaemorrhagiae. CgMLST subtyping revealed a diversity of clonal groups (CGs) distributed in several regional clusters. Besides validating a robust recruitment and sampling process, this study outlines the value of combining PCR and serological testing when suspecting leptospirosis and the usefulness of implementing molecular typing methods to identify circulating field strains. It also confirms the epidemiological importance of the Australis serogroup and allows for the collection of different highly pathogenic strains for vaccine development.

PSLBI-28 Assessing the impact of a potential canine vaccine for the control of Chagas Disease

PSLBI-28 Assessing the impact of a potential canine vaccine for the control of Chagas Disease

H3N2 canine influenza virus-like particle vaccine with great protection in beagle dogs.

A new antigenically and genetically distinct canine influenza virus (CIV) H3N2 clade possessing mutations associated with mammalian adaptation emerged in 2016 and substituted previously circulating strains. This clade poses a risk for zoonotic infection. In our study, intramuscular injection of the H3N2 virus-like particle (VLP) vaccine and inactivated H3N2 CIV confer completely sterilizing protection against homologous H3N2 canine influenza virus challenge. Our results provide further support for the possibility of developing VLP vaccines that can reliably induce immunity in animal species.

Rabies in rural northeast India: A case report emphasising the urgency of the One Health approach

Dog-mediated rabies is endemic in India. The country records the highest mortality due to dog-bite-related rabies despite the availability of interventions to prevent deaths. We present a case study of the death of a 59-year-old man in a suburban town of Northeast India after a dog bite from an owned pup. Through this case study, we investigate various omissions and commissions in communities and health professionals that make rabies rampant in India. The circumstances surrounding the death were investigated by interviewing the wife, relatives, neighbour, the hospital/nursing home where the bite case was reported, the district Rapid Response Team (RRT), and the Veterinary and Animal Health Department Officer and through the information recorded in the disease outbreak report. While the biting animal was not vaccinated and had no restriction over its movement imposed by the owners, the response of the hospital staff and public authorities was delayed and inadequate. A poignant reminder of the complexities surrounding dog-mediated rabies in India, this case study calls for a holistic protocol to address dog bites through ensuring the One Health approach encompassing education, provision of post-exposure prophylaxis (PEP) and canine rabies vaccines for dogs, promotion of responsible dog ownership, and intersectoral collaboration. Moreover, strengthening communication channels through effective data exchange and encouraging synergy among healthcare, veterinary, and public health sectors is indispensable to maximize the impact of rabies prevention and control interventions.

Review of leptospirosis in dogs from Mexico: Epidemiology, diagnosis, prevention, and treatment.

Leptospirosis, classified by the World Health Organization as an emerging and neglected disease, is caused by the zoonotic pathogen Leptospira interrogans. This review aims to outline the Mexican epidemic of L. interrogans in dogs, including diagnosis and prevention methods. This review article searched articles from the publishers Wiley, Springer, PubMed, Redalyc, SciElo, and Elsevier. Among the 200 Mexican articles concerning Leptospira epidemiology, diagnosis, treatment, and vaccination, those that failed to meet the set inclusion criteria were excluded. The worldwide study of L. interrogans has focused on this bacterium. In Mexico, up-to-date information on canine prevalence, diagnosis, and vaccine use is scarce. Flow cytometrically detected Salmonella serovars differ from those in current vaccines, emphasizing the importance of broadening vaccine serovar coverage.

Dog ecology and rabies control including canine vaccination coverage: Impacts from a survey in Madagascar.

Rabies virus (RABV; species Lyssavirus rabies) is causing one of the oldest zoonotic diseases known to mankind, leading to fatal encephalomyelitis in animals and humans. Despite the existence of safe and effective vaccines to prevent the disease, an estimated 99% of human rabies deaths worldwide are caused by dog-mediated rabies with children at the highest risk of infection. Rabies has been endemic in Madagascar for over a century, yet there has been little research evaluating local knowledge and practices impacting on the rabies control and prevention. Thus, this study was undertaken to better understand the dog ecology including canine vaccine coverage and to assess knowledge and practices of dog owners and veterinarians. A cross-sectional study was conducted among 123 dog-owning households in thirteen fokontanys in Mahajanga from July 4 to September 13, 2016. Single and multi-member dog-owning households in the study area on the day of the interview were eligible for inclusion and purposively selected with the support of a local guide. The survey included a household questionnaire capturing information on the dog's demographics, husbandry practices, knowledge and practices towards rabies and its control measures; the dog ecology questionnaire collected dog characteristics, vaccination status and husbandry practices. All households that reported a dog bite incident, were invited to participate in a dog bite questionnaire. In addition, direct observations of roaming dogs were conducted to assess dog population demographics and to document behavioural characteristics. Two veterinarians were purposively selected and took part in an interview during the survey period, providing information on rabies control activities, including dog-care practices in the area. Descriptive and inferential data analyses were performed using Epi Info version 7.1.5.0 (CDC Atlanta, USA). We recorded a total of 400 dogs, of which 338 (84.5%) were owned amongst 123 households. More than half (67.8%) of owned dogs were between 1 to 5 years old and 95.6% were kept for guarding purposes. 45% of the surveyed dogs had free access to roam outside the premises. The majority (85.4%) of dog owners were knowledgeable that a dog bite could potentially transmit RABV to humans. 19 dog bites were reported and of these 73.6% were caused by the owner's or a neighbour's dog. In 6 of the 19 cases, children between 7 and 15 years of age were the victims. Dog vaccination coverage against rabies was 34% among owned dogs. Of the participants aware of a veterinarian, the majority (55/82) indicated that they accessed veterinarian services at irregular intervals. The main obstacles to vaccinations cited by dog owners were limited financial resources and difficulty accessing veterinary care. This study contributes to enhanced understanding of the dog ecology including canine vaccine coverage as well as knowledge and practices of dog owners in Madagascar. Most dogs in the study area were accessible for preventive vaccination through their owners, however only one third of the investigated canine population was vaccinated against rabies. Concerted national efforts towards rabies prevention and control should aim to address financial challenges and access to veterinary services.

Comparative structural and immunological analysis of outer membrane proteins and dermonecrotic toxin in Bordetella bronchiseptica canine isolate

Bordetella bronchiseptica is a pathogen causing respiratory infections in mammals. With the improving understanding of companion animals’ welfare, addressing the side effects of bordetella vaccine gains importance in dogs. Studies on diverse subunit vaccines are actively pursued in humans to safely and effectively control bordetellosis. Therefore, our objective was to develop a canine bordetella vaccine inspired by human vaccine development. We evaluated the immunogenicity of the two bacterial components: the outer membrane proteins (OMPs) and the dermonecrotic toxin (DNT) from a canine isolate of B. bronchiseptica. In-silico analysis identified eight domains of DNT, and Domain 3 was selected as the most promising antigen candidate. Additionally, the OMPs were extracted and examined using SDS-PAGE and Western blot analysis. The distinct immunological characteristic of OMPs and DNT-3 were examined individually and in combination. Gene expression and cytokine production were also evaluated in DH82 cells after stimulation with those antigens. Treatment with OMPs resulted in higher level of Th1 related cytokines, while DNT-3 induced a predominant response associated with Th17 and Th2 in the cytokine production. Synergistic effects were observed exclusively on IL-23, indicating increase of a potential risk of side effects when OMPs and DNT act together. These findings provide valuable insights into the reactogenicity of conventional Bordetella vaccines. Further, the presented preclinical data in this study offer an alternative method of the development for an optimal next-generation Bordetella vaccine for companion animals and humans, replacing the acellular vaccines containing both toxin and protein components.

Single-domain antibodies reveal unique borrelicidal epitopes on the Lyme disease vaccine antigen, outer surface protein A (OspA).

Camelid-derived, single-domain antibodies (VHHs) have proven to be extremely powerful tools in defining the antigenic landscape of immunologically heterogeneous surface proteins. In this report, we generated a phage-displayed VHH library directed against the candidate Lyme disease vaccine antigen, outer surface protein A (OspA). Two alpacas were immunized with recombinant OspA serotype 1 from Borrelia burgdorferi sensu stricto strain B31, in combination with the canine vaccine RECOMBITEK Lyme containing lipidated OspA. The phage library was subjected to two rounds of affinity enrichment ("panning") against recombinant OspA, yielding 21 unique VHHs within two epitope bins, as determined through competition enzyme linked immunosorbent assays (ELISAs) with a panel of OspA-specific human monoclonal antibodies. Epitope refinement was conducted by hydrogen exchange-mass spectrometry. Six of the monovalent VHHs were expressed as human IgG1-Fc fusion proteins and shown to have functional properties associated with protective human monoclonal antibodies, including B. burgdorferi agglutination, outer membrane damage, and complement-dependent borreliacidal activity. The VHHs displayed unique reactivity profiles with the seven OspA serotypes associated with B. burgdorferi genospecies in the United States and Europe consistent with there being unique epitopes across OspA serotypes that should be considered when designing and evaluating multivalent Lyme disease vaccines.

Comparative evaluation of Borrelia burgdorferi antibody detection between the VetScan Flex4 and SNAP 4Dx Plus

Two studies were developed to compare Borrelia burgdorferi antibody detection between the VetScan Flex4 and SNAP 4Dx Plus tests. The objective of the first study was to evaluate the diagnostic sensitivity (Se) and specificity (Sp) of VetScan Flex4 and SNAP 4Dx Plus B. burgdorferi results using field sourced samples compared to a Western Blot reference method. The sensitivity and specificity of VetScan Flex4 were 81.9 % (95 % CI: 71.9 %-89.5 %) and 89.3 % (95 % CI: 85.2 %-92.9 %) respectively, and SNAP 4Dx Plus's sensitivity and specificity were 80.7 % (95 % CI: 70.6 %-88.6 %) and 92.8 % (95 % CI: 89.1 %-95.5 %) respectively. When comparing VetScan Flex4 and Snap 4Dx Plus, the Simple Kappa Coefficient estimate was 0.76 (95 % CI: 0.69-0.84) indicating substantial agreement between the two methods. McNemar's Test revealed concordance between the two methods was not statistically significant (P = 0.05). The objective of the second study was to evaluate whether VetScan Flex4 differentiates between B. burgdorferi antibodies derived from infection versus vaccination with commonly used canine Lyme vaccines. The sensitivity and specificity of the VetScan Flex4 in differentiating canine Lyme vaccination from infection with Borrelia burgdorferi were 100 % (Se 95 % CI: 78.2 %-100 %; Sp 95 % CI: 91.2 %-100 %). In conclusion, the VetScan Flex4 is a reliably sensitive and specific point-of-care test that is similar to Snap 4Dx Plus, can differentiate between infection and Lyme vaccination, and can be utilized by veterinarians for Lyme disease diagnosis and surveillance of B. burgdorferi exposure.

Challenges in Developing Effective Canine Infectious Respiratory Disease Vaccines

Challenges in Developing Effective Canine Infectious Respiratory Disease Vaccines

Determination of immunogenicity and potency of canine anti-rabies vaccines marketed in Sri Lanka: A Proposal on an experimental study using rabbits as the animal model and field study using sample dog population.

Anti-rabies vaccines (ARVs) with good immunogenic capacity play an important role in controlling the deadly zoonotic rabies in Sri Lanka. The ARVs currently marketed in the country have not been tested for their efficacy and potency at the local level before being released to the market. This article outlines the proposed project formulated to determine the efficacy and potency of these ARVs in generating immunity against rabies. The authors propose that this project will be articulated in three main categories. Part I will be the immunogenicity measurement using, New Zealand White rabbits as the animal model. Part II will be a field study with a sample dog population, including domestic and free-roaming dogs and Part III will be the potency testing of the ARVs using the mouse challenge test. Immunogenicity will be assessed by measuring the humoral immunity development following vaccination, using the methods of Florescent Antibody Virus Neutralization (FAVN) and ELISA. The project will be conducted in collaboration with WHO/WOAH Reference Laboratory for Rabies in Nancy, France, and Medical Research Institute, Colombo 08, Sri Lanka.

A Comparative Analysis of Canine Rabies Vaccines

In order to prevent rabies in dogs, vaccination is the most practical solution. The immunogenicity of vaccination is assessed using specific rabies virus ELISA kits. We conducted this study to measure the immune response induced by three selected vaccines, Multikan 8, Biocan R, and Nobivac Rabies, among dogs. ELISA testing was conducted in Azerbaijan for the first time in order to measure vaccines’ ability to generate antibodies, and vaccines were compared.

Breed, smaller weight, and multiple injections are associated with increased adverse event reports within three days following canine vaccine administration.

To evaluate patient and vaccine factors associated with adverse events (AEs) recorded within 3 days of vaccine administration in a large cohort of dogs. 4,654,187 dogs vaccinated in 16,087,455 office visits in a 5-year period at 1,119 hospitals of a corporate practice. Electronic medical records of dogs vaccinated between January 1, 2016, and December 31, 2020, were searched for diagnoses of possible AEs recorded within 3 days of administration of vaccines without concurrent injectable heartworm preventative. Patient risk factors (age, sex, breed, and weight) and number and type of vaccine were extracted from records. ORs (and 95% CIs) for risk factors were estimated via multivariable logistic regression mixed models with patient as a random effect. AEs were recorded following 31,197 vaccination visits (0.19%, or 19.4/10,000 visits). Reported AE rates increased from 1 to 4 vaccines administered and among individual vaccines were greatest for rabies vaccine. AE rate was generally inversely related to body weight, with largest rates in dogs ≤ 5 kg. The largest AE rates were noted in French Bulldogs and Dachshunds (ORs > 4 compared to mixed-breed dogs). Risk factor information can be used to update vaccination protocols and client communication. Breed differences may indicate genetics as the primary risk factor for adverse vaccine reactions following vaccinations.

Development of a Novel Canine Parvovirus Vaccine Capable of Stimulating Protective Immunity in Four-Week-Old Puppies in the Face of High Levels of Maternal Antibodies.

Many highly effective vaccines have been developed to protect dogs against disease caused by canine parvovirus, but despite this vaccine interference by maternally derived antibodies continues to cause immunisation failure. To help overcome this limitation we have developed a novel, recombinant canine parvovirus type 2c vaccine strain, based on the structural and non-structural elements of an established type 2 vaccine. This novel CPV-2c vaccine strain has unique efficacy in the field, it is able to induce sterilising immunity in naïve animals 3 days after vaccination and is able to overcome very high levels of maternally derived antibodies from 4 weeks of age-thus closing the immunity gap to canine parvovirus infection in young puppies. The vaccine strain, named 630a, has been combined with an established canine distemper virus Onderstepoort vaccine strain to produce a new bivalent vaccine (Nobivac DP PLUS), intended to immunise very young puppies in the face of high levels of maternally derived antibody. Here, we describe the onset of immunity and maternal antibody interference studies that support the unique efficacy of the strain, and present overdose studies in both dogs and cats that demonstrate the vaccine to be safe.

Sick as a dog? The prevalence, politicization, and health policy consequences of canine vaccine hesitancy (CVH)

Canine vaccine hesitancy (CVH) can be thought about as dog owners’ skepticism about the safety and efficacy of administering routine vaccinations to their dogs. CVH is problematic not only because it may inspire vaccine refusal – which may in turn facilitate infectious disease spread in both canine and human populations – but because it may contribute to veterinary care provider mental/physical health risks. In a nationally representative survey of US adults (N = 2200), we introduce a novel survey-based instrument for measuring CVH. We document pervasive CVH in dog owner subpopulations. Troublingly, we find that CVH is associated with rabies non-vaccination, as well as opposition to evidence-based vaccine policies. We conclude by discussing the human and animal health consequences of CVH, and outline a research agenda for future opinion-based research on this important topic.

Establishment and evaluation of a multiplex real-time RT-PCR for quantitative and differential detection of wild-type canine distemper virus from vaccine strains

This study sought to establish a real-time reverse transcription (RT)-PCR method to differentially detect canine distemper virus (CDV) wild-type and vaccine strains. To this end, a pair of CDV universal primers and two specific minor groove binder (MGB) probes, harboring a T/C substitution in the hemagglutinin (H) gene, were designed. Using a recombinant plasmid expressing the H gene of the CDV wild-type or vaccine strain as standards, a sensitive and specific multiplex real-time RT-PCR was established for quantitative and differential detection of CDV wild-type and vaccine strains. The limit of detection for this multiplex assay was 22.5 copies/μL and 2.98 copies/μL of viral RNA for wild-type and vaccine strains, respectively. Importantly, the wild-type and vaccine MGB probes specifically hybridized different genotypes of wild-type CDV circulating in China as well as globally administered vaccine viruses, respectively, with no cross-reactivity observed with non-CDV viruses. Moreover, this method was successfully applied for the quantitative detection of CDV RNA in tissue samples of experimentally infected breeding foxes, raccoon dogs, and minks. Additionally, the multiplex real-time RT-PCR was able to detect the viral RNA in the whole blood samples as early as 3 days post-infection, 3 to 4 days prior to the onset of clinical signs in these CDV infection animals. Hence, the established multiplex real-time RT-PCR method is useful for differentiating wild-type CDV and vaccine strains in China, and for conducting canine distemper early diagnosis as well as dynamic mechanism of CDV replication studies in vivo.