VACCINATION FOR BORDETELLA BRONCHISEPTICA IN DOGS: THE ARGUMENT FOR PRIME-BOOST VACCINATION STRATEGIES DR. STEPHAN CAREY, DVM, PHD, DACVIM (continued)
The variety of vaccination options contributes to controversy and confusion over which vaccination strategy evokes an optimal immune response and provides the best protection 7 . Available laboratory studies and field trials suggest that all currently available licensed Bordetella bronchiseptica vaccines are effective in reducing or preventing clinical signs of disease. In general, these vaccines all provide this protection by stimulating an adaptive immune response against Bordetella bronchiseptica antigens. The ways in which mucosal vaccines (oral and intranasal) and parenteral vaccines stimulate adaptive immunity differ. These different routes of vaccination also confer additional benefits that can help enhance immune responses and protection. 5 MUCOSAL BORDETELLA BRONCHISEPTICA VACCINES Oral and intranasal Bordetella bronchiseptica vaccines both generate adaptive immune responses via antigen presentation to mucosal- associated lymphoid tissues (MALTs) in the upper respiratory tract. Intranasal or oral application of vaccine antigen stimulates the production of Immunoglobulin A (IgA) -producing plasma cells in the subepithelial space. Most of this antigen-specific IgA is translocated through epithelial cells and deposited on the airway surface within the epithelial lining fluid. At this location, IgA is very effective at binding airborne pathogens that are deposited into the epithelial lining fluid, thus inhibiting their attachment to the
airway surface. High concentrations of mucosal IgA have the potential to “prevent” infection, and mediate protection via immune exclusion . In addition to stimulating local production of IgA, mucosal vaccines offer other immunologic advantages to the host. Mucosal vaccines are effective after a single dose in naïve patients. Oral and intranasal Bordetella bronchiseptica vaccines are not inhibited by maternally derived antibodies, and are therefore capable of stimulating vaccine-induced immune responses in puppies as young as 3 to 4 weeks of age 8 . By priming immune responses in the upper respiratory tract, mucosal vaccines can affect mucosal homing, which localizes pathogen- specific memory immune cells to the sites where initial colonization and infection typically occur 9 . Modified live mucosal vaccines can also activate innate immune responses in the same mechanism employed by natural pathogens. The non-specific nature of innate immune responses can potentially be used strategically to activate local immune responses, making the environment unfavorable for infection prior to an anticipated challenge 10 . 6 PARENTERAL BORDETELLA BRONCHISEPTICA VACCINES Following subcutaneous injection, parenteral Bordetella bronchiseptica vaccines are processed by tissue antigen presenting cells and delivered to lymphoid cells in regional lymph nodes. This type of vaccination stimulates the proliferation of IgG- producing plasma cells in lymph nodes,
the spleen, and in circulation, and produces high concentrations of IgG in plasma 11,12 . While vaccine-induced IgG is largely sequestered in the plasma in health, its small size allows it to leak through the microvasculature and reach mucosal surfaces at sites of inflammation. Unlike IgA, IgG possesses functional properties that destroy or kill bacterial pathogens, including potent opsonization (recruitment and signaling of phagocytic cells) and activation of the complement cascade 12 . By triggering bacterial killing mechanisms at sites of colonization or infection, IgG mediates protection via immune elimination . In this way, circulating IgG provides an important “backup” that limits tissue invasion and prevents severe infection and systemic dissemination when pathogens evade or overwhelm mucosal immune mechanisms 13 . An important immunologic advantage provided by parenteral vaccination is the ability to serially “boost” a primed immune response. The nature of a mucosal immune response (immune exclusion) makes it difficult to boost an existing immune response with multiple doses of a mucosal vaccine 14 . Because parenteral vaccines bypass mucosal surfaces, they can be administered repeatedly in an effort to amplify an existing immune response within a short window of time. This serial parenteral vaccination strategy provides the immunologic basis for vaccine schedules recommended by the CDC for early life protection of children against Bordetella pertussis 15 . (continued)
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