Original research

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

Garry L Morefield¹ , Ralph F Tammariello² , Bret K Purcell³ , Patricia L Worsham³ , Jennifer Chapman⁴ , Leonard A Smith² , Jason B Alarcon⁵ , John A Mikszta⁵ and Robert G Ulrich¹

¹Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA

²Molecular Biology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA

³Bacteriology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA

⁴Pathology Divisions, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA

⁵Becton Dickinson Technologies, Research Triangle Park, NC, USA

author email corresponding author email

Journal of Immune Based Therapies and Vaccines 2008, 6:5doi:10.1186/1476-8518-6-5

Published:	3 September 2008

Abstract

Background

Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.

Methods

As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures.

Results

The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. 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.

Conclusion

Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component.

The vaccination method we describe 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.