Strategies for development of combination vaccines

Background. The increasing complexity of the recommended childhood immuniza tion schedule has resulted in the need for combination vaccines. Methods. Through an extensive review of the current literature, various str ategies and issues related to the development of combination vaccines are d iscussed. Results. Issues that should be considered when combining vaccine components include the current childhood immunization schedule, compatibility of comp onents, availability of antigens for targeted diseases, safety, efficacy, i mmunogenicity and route of delivery. When choosing an appropriate combinati on of antigen(s)/serotype(s) for a global or national formulation, careful consideration must be made when selecting serotypes to combine depending on the market or area of use. It is important to know that potential interact ions can involve other components of the vaccines, including buffers, adjuv ants and preservatives. The Food and Drug Administration requires that the combination not only have immunogenicity comparable with those of the compo nent vaccines, but that its safety profile be comparable with the most reac togenic component. The Food and Drug Administration also recommends that a test of noninferiority be performed, such that the combination performs sim ilarly to the separate components with regard to antibody titers. Conclusions. Combination vaccines are critical to the success of vaccinatio n programs, and each new combination must be carefully studied to ensure co mparable safety and immunogenicity of the individual components.