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
This Brief includes a Technical Support Package (TSP).
An Alternative Approach to Combination Vaccines
(reference ARL-0061) is currently available for download from the TSP library.
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Overview
The document presents research on an innovative approach to vaccination, focusing on the intradermal administration of isolated vaccine components to protect against multiple diseases, specifically anthrax, botulism, plague, and staphylococcal toxic shock. As the number of vaccines continues to grow, the challenge of administering multiple vaccines simultaneously due to potential incompatibilities arises. This study suggests that delivering each antigen to physically isolated sites within the skin can circumvent these issues, allowing for effective vaccination without the need for combination vaccines.
The research involved rhesus macaques, which were vaccinated with arrays of the aforementioned vaccines. The results demonstrated that the vaccinated primates exhibited robust antibody responses and were well-tolerated, showing no adverse effects from the intradermal administration. Importantly, the vaccinated animals were completely protected from lethal challenges posed by Bacillus anthracis spores, botulinum neurotoxin A, and staphylococcal enterotoxin B. They also showed partial protection against Yersinia pestis, the causative agent of plague.
The findings indicate that there are no biological limitations to the number of vaccines that can be administered using this method, suggesting a practical alternative to traditional vaccine mixtures. This approach could significantly reduce the number of vaccinations required, addressing public health concerns regarding patient compliance with vaccination schedules, especially as the number of recommended vaccines continues to rise.
The document also highlights the broader implications of vaccination for public health, noting the substantial cost savings associated with preventing diseases through vaccination. With 28 recommended vaccines for children and adults, plus annual influenza shots, developing a reasonable vaccination schedule is crucial for ensuring compliance and maximizing public health benefits.
In summary, this research offers a promising strategy for enhancing vaccination efficacy and safety by utilizing intradermal delivery of isolated vaccine components. This method not only maintains strong immune responses but also provides a viable solution to the challenges posed by increasing vaccination requirements in public health.
