An Alternative Approach to Combination Vaccines
- Created on Friday, 01 January 2010
Vaccines administered intradermally protect against multiple diseases.
As the number of investigational and approved vaccines continues to increase, the frequency of vaccinations will soon reach a practical limit. The development of combination vaccines is a common practice that addresses the concern of repeated visits to the clinic by reducing the total number of injections required compared with administration schedules for the monovalent vaccines. Yet, physical, chemical, and biological interactions among the components of combination vaccines must be considered to avoid detrimental effects on safety or efficacy. For example, when the Haemophilus influenzae type b (Hib) vaccine was combined with diphtheria, tetanus, and acellular pertussis vaccine, a decrease in antibody titer for the Hib vaccine was observed. Thus, there is a need to develop new approaches for delivery of multiple vaccines.
A method of protective vaccination against multiple diseases by intradermal administration of each antigen to physically isolated sites is being investigated. This method is aimed at avoiding potentially incompatible vaccine mixtures. As a possible alternative to combination vaccines, specially designed microneedles are used to inject four separate recombinant protein vaccines for anthrax, botulism, plague, and staphylococcal toxic shock next to each other just below the surface of the skin.
The delivery of multiple vaccines intradermally was evaluated to physically isolate each component, thus directly preventing formulation incompatibilities prior to administration. The physiological fate of vaccines administered intradermally is not known. However, vaccination by microneedles permits verification of the physical deposition into the skin, while intramuscular injection sites are inaccessible for direct observation. Further, intradermal vaccination using microneedles is less painful than intramuscular injection by conventional needles and provides an increased immune response with a lower amount of vaccine than that required by intramuscular methods.
The intradermally administered vaccines retained potent antibody responses and were well tolerated. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B.
The physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of any component vaccine. Further, the vaccination method described may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product. The results demonstrate that intradermal delivery of multiple vaccine preparations may provide a practical alternative to traditional combination vaccines and complicated administration schedules.
This work was done by Garry L. Morefield, Ralph F. Tammariello, Bret K. Purcell, Patricia L. Worsham, Jennifer Chapman, Leonard A. Smith, and Robert G. Ulrich of the Army Medical Research Institute of Infectious Diseases; and Jason B. Alarcon and John A. Mikszta of Becton Dickinson Tech nologies. For more information, download the Technical Support Package (free white paper) at www.techbriefs.com/tsp under the Bio-Medical category. ARL-0061