multiple antigens could possibly lead to polyclonal activation of the immune system. Webb (1997) has speculated that multiple vaccinations may shift the immune response to a Th2 profile that favors hypersensitivity responses. However, others have suggested that vaccinations may induce protective Th1 responses that should prevent the development of atopic disease (Barnes, 1999; Holt et al., 1999).
Animal studies involving multiple vaccinations examine three categories of adverse effects: those specific to an individual vaccine (adverse health outcomes for anthrax and botulinum vaccines individually have been discussed earlier in this chapter), reduced protection to one antigen when the immune system is coping with multiple antigens simultaneously, and the development of adverse immunological reactions.
In examining animal studies on multiple vaccinations, the committee focused on studies in which at least one of the immunogens was the anthrax or botulinum vaccine. The committee did not examine the extensive literature on animal studies of vaccine combinations that have been in use for many years (use of the DTP vaccine began in the 1940s, and the MMR vaccine was approved in 1971; Plotkin and Mortimer, 1994).
Alteration in the protective effect of the vaccination. Multiple vaccinations may lead to an insufficient protective response to one or several of the antigens. Pilipenko and Miroshnichenko (1963) found that simultaneous injections of live vaccines for anthrax, plague, tularemia, and brucellosis in guinea pigs reduced the development of protective immunity to anthrax without adversely affecting the response to the other live vaccines. The only adverse effect of the vaccination itself was erythema and an infiltrate at the site of injection of the live spore anthrax vaccine, a response that resolved within 3 to 5 days. A similar study by Borodko and Samsonovich (1965) in guinea pigs reported a reduced immune response to all of the four antigens as determined by allergic skin responses and challenge with the infectious agent. The authors did not mention adverse effects from the vaccination.
In the following animal studies, the degree of protective immunity was unaffected by multiple vaccinations. In sheep, Safarov and Ibragimov (1968) investigated the combination of vaccination with live spore anthrax vaccine and the standard vaccine for braxy and infectious enterotoxemia. The studies did not mention any adverse effects from the vaccination itself. A study by Zuffa and colleagues (1972) combined vaccination with botulinum toxoid types C and D and vaccination for the viral Aujeszky’s disease in mink; the authors did not discuss adverse effects. A similar study by Gorski and Motz (1984) found that vaccination with distemper virus at the same time as administration of botulinum type C toxoid did not affect immunity. The botulinum toxoid caused a small area of skin swelling that was evident for 2 weeks. Another study with