Strategies for development of combination vaccines.

Abstract

The increasing complexity of the recommended childhood immunization schedule has resulted in the need for combination vaccines. Through an extensive review of the current literature, various strategies and issues related to the development of combination vaccines are discussed. Issues that should be considered when combining vaccine components include the current childhood immunization schedule, compatibility of components, availability of antigens for targeted diseases, safety, efficacy, immunogenicity and route of delivery. When choosing an appropriate combination 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 interactions can involve other components of the vaccines, including buffers, adjuvants and preservatives. The Food and Drug Administration requires that the combination not only have immunogenicity comparable with those of the component vaccines, but that its safety profile be comparable with the most reactogenic component. The Food and Drug Administration also recommends that a test of noninferiority be performed, such that the combination performs similarly to the separate components with regard to antibody titers. Combination vaccines are critical to the success of vaccination programs, and each new combination must be carefully studied to ensure comparable safety and immunogenicity of the individual components.