Bordetella, Canine Parainfluenza, and Canine Influenza
Previously evaluated74 challenge of immunity studies in Bordetella bronchiseptica (Bb)-seronegative beagle puppies have provided variably convincing evidence of the efficacy of inactivated injectable, modified-live combination IN and single-component oral vaccines for Bb. More recently, current combination IN and single-component oral vaccines for Bb have been directly compared.75,76 Data from these studies75,76 are conflicting concerning the equivalency of the oral versus IN route in conferring immunity; one showed no difference between routes,75 whereas the other demonstrated superior clinical efficacy of the IN route.76 Altogether, available data indicate that commercial vaccines for Bb all “work” at some level, regardless of the route of administration.74–76 However, in general, the IN (versus oral) route of administration is preferable for respiratory pathogens. This is because it has been recognized that the common mucosal immune system, as originally conceptualized, was an oversimplification and that there is compartmentalization of mucosal immune responses, at least to some extent, making IN delivery of antigen more effective than oral at stimulating responses in the respiratory tract.77–83
There may be an immunological benefit in combining different vaccines and routes of administration in a primary series. This strategy is called “heterologous prime-boost” and involves administering different forms of an antigen by different routes to broaden and extend a response.83 Although little studied in small animal veterinary medicine, there is an extensive comparative literature,78 including a dog-relevant Bordetella pertussis murine model,84 supporting this approach. Currently, heterologous prime-boost is being widely investigated in an effort to improve responses to vaccines for COVID-19.85 One study using a combination of IN and injectable (whole-cell bacterin) Bb vaccines demonstrated a significant clinical benefit to this approach versus either vaccine alone.86 However, this strategy has not yet been evaluated with current canine vaccines for Bb or other pathogens.
Concerning boosting of Bb vaccines, current combination IN and single-component acellular injectable Bb vaccines have been shown to induce equivalent anamnestic (memory) Bb-specific IgG and IgA responses when used as booster vaccines in previously immunized adult household dogs.87 There are no similar published studies concerning the use of the single-component oral vaccine for this purpose or any use in household dogs.
Dogs that are at risk for Bb are also at risk for canine parainfluenza virus (CPIV) and canine adenovirus virus-2 (CAV-2) and should be vaccinated for all three pathogens.88,89 Only the current combination IN and injectable (core) vaccines contain these pathogens. Therefore, the use of single-component oral and injectable Bb vaccines is not recommended. Exceptions include dogs that cannot be vaccinated IN, or in the case where the injectable Bb vaccine is used simultaneously with the injectable core vaccines as a booster for IN primed responses in a puppy series.85,86 If an IN (modified-live) Bb vaccine is inadvertently administered by injection, the vaccine package insert or manufacturer should be consulted, as resulting inflammatory reactions can be serious.90
Duration of immunity and related recommendations for annual vaccination for Bb and CPIV are largely based on experimental infections in seronegative laboratory beagle puppies.74,91,92 Such studies, usually conducted at peak immune response after vaccination, can generally accurately assess the ability of a vaccine to reduce disease. However, the validity of using such studies employing group-housed, genetically similar subjects to determine DOI conferred by vaccines to household dogs is questionable. It is difficult to model heterogeneous household conditions comprising the plethora of the host, environmental and pathogen cofactors that can contribute to the brevity or longevity of protective clinical immunity. The latter endeavor requires well-designed and well-conducted field trials, including disease reporting; however, these types of studies are rare. One seminal study of the natural history of Bb indicated that the duration of clinical immunity (reduction of disease) may be as short as ~6 mo.93 The duration of clinical immunity to CPIV in household dogs is unknown.91 Therefore, for patients at high risk for CPIV and Bb, it may be advantageous to use IN combination Bb and CPIV vaccines more frequently than annually, for example, before boarding. In addition to boosting adaptive immune responses, the latter practice may better ameliorate disease through stimulation of the local innate immune response (type 1 interferon),94 although this is poorly documented in small animals.
Canine influenza virus (CIV) serotypes H3N8 and H3N2 have been documented in North America and other parts of the world.95 Disease caused by these viruses is usually indistinguishable from that caused by other respiratory pathogens associated with canine infectious respiratory disease (CIRD), although severe and sometimes fatal disease can occur in CIV-infected dogs. In contrast to CPIV, which tends to be endemic, or at least prevalent, in canine populations, 88,89 CIV infections and clinical disease to date have occurred as multicentric nonsustaining outbreaks.95 Therefore, the routine use of CIV vaccines in all dogs is currently not recommended. Etiologic diagnoses of CIRD cases using quantitative polymerase chain reaction respiratory pathogen panels, together with monitoring of the current circulation of CIV (https://www.vet.cornell.edu/animal-health-diagnostic-center/news/canine-influenza-civ-updates), should be used to determine whether CIV vaccination is warranted in individual dogs, especially in dogs that are boarded and otherwise commingled at dog daycare, dog parks, dog shows and agility events, and in dogs who travel. Although immunity to influenza viruses is primarily serotype-specific, the use of bivalent CIV vaccines may avoid skewing of responses to one serotype.96 This could broaden protective immunity and is therefore recommended.