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

Morefield GL, Tammariello RF, Purcell BK, Worsham PL, Chapman J, Smith LA, Alarcon JB, Mikszta JA, Ulrich RG - J Immune Based Ther Vaccines (2008)

Bottom Line: Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. rulrich@bioanalysis.org.

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.

No MeSH data available.


Related in: MedlinePlus

Intradermal administration of the vaccines for anthrax (rPA), botulism [BoNT/A(Hc)], plague (rF1-V), and SEB induced toxic-shock (STEBVax). A. Rhesus macaque skin immediately after vaccination (two sites, left to right): BoNT/A, rF1-V, rPA, and STEBVax. B. Rhesus macaque skin two months after vaccine administration. Marks are adjacent to injection sites. C. Skin sections (H&E stain) obtained from the vaccine delivery site exhibited epithelioid macrophages and multinucleated giant cells containing adjuvant (inset, green). Phalloidin staining of actin, red; Hoechst staining of DNA, blue. D. Macrophages at the vaccine delivery site exhibited high expression of MHC-II molecules (brown). Anti-MHC Class II immunohistochemistry (brown). E. Epithelioid macrophages (H&E stain) containing adjuvant (inset) were also present in the axillary lymph nodes of vaccinated animals. F. Vaccination did not significantly alter white blood cell counts of vaccinated animals (solid line) compared to control (dashed line). Mean cell counts ± SD of all animals studied.
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Figure 1: Intradermal administration of the vaccines for anthrax (rPA), botulism [BoNT/A(Hc)], plague (rF1-V), and SEB induced toxic-shock (STEBVax). A. Rhesus macaque skin immediately after vaccination (two sites, left to right): BoNT/A, rF1-V, rPA, and STEBVax. B. Rhesus macaque skin two months after vaccine administration. Marks are adjacent to injection sites. C. Skin sections (H&E stain) obtained from the vaccine delivery site exhibited epithelioid macrophages and multinucleated giant cells containing adjuvant (inset, green). Phalloidin staining of actin, red; Hoechst staining of DNA, blue. D. Macrophages at the vaccine delivery site exhibited high expression of MHC-II molecules (brown). Anti-MHC Class II immunohistochemistry (brown). E. Epithelioid macrophages (H&E stain) containing adjuvant (inset) were also present in the axillary lymph nodes of vaccinated animals. F. Vaccination did not significantly alter white blood cell counts of vaccinated animals (solid line) compared to control (dashed line). Mean cell counts ± SD of all animals studied.

Mentions: A simple mixture of the BoNT/A(Hc), F1-V, rPA and STEBVax as currently formulated resulted in formation of a precipitation and a significant change in pH of the solution (data not shown). Because of these apparent chemical incompatibilities we were not able to examine animals vaccinated with simple mixtures of the vaccines. The vaccines BoNT/A(Hc), F1-V, rPA and STEBVax were individually administered three times, 28 d apart, by injection into the shaved dermis of the upper arm or thigh of rhesus macaques using stainless steel microneedles that were the approximate diameter of a human hair, as previously reported [18-21]. The subject animals received doses of each vaccine that were independently optimized [11,13,17,19] and adsorbed to aluminum hydroxide adjuvant (AH). Control animals received i.d. injections of AH alone. The pattern of vaccinations consisted of an array of 100-μl injections separated by 2 cm, keeping each vaccine isolated from adjacent administrations (Fig. 1).


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

Morefield GL, Tammariello RF, Purcell BK, Worsham PL, Chapman J, Smith LA, Alarcon JB, Mikszta JA, Ulrich RG - J Immune Based Ther Vaccines (2008)

Intradermal administration of the vaccines for anthrax (rPA), botulism [BoNT/A(Hc)], plague (rF1-V), and SEB induced toxic-shock (STEBVax). A. Rhesus macaque skin immediately after vaccination (two sites, left to right): BoNT/A, rF1-V, rPA, and STEBVax. B. Rhesus macaque skin two months after vaccine administration. Marks are adjacent to injection sites. C. Skin sections (H&E stain) obtained from the vaccine delivery site exhibited epithelioid macrophages and multinucleated giant cells containing adjuvant (inset, green). Phalloidin staining of actin, red; Hoechst staining of DNA, blue. D. Macrophages at the vaccine delivery site exhibited high expression of MHC-II molecules (brown). Anti-MHC Class II immunohistochemistry (brown). E. Epithelioid macrophages (H&E stain) containing adjuvant (inset) were also present in the axillary lymph nodes of vaccinated animals. F. Vaccination did not significantly alter white blood cell counts of vaccinated animals (solid line) compared to control (dashed line). Mean cell counts ± SD of all animals studied.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2543000&req=5

Figure 1: Intradermal administration of the vaccines for anthrax (rPA), botulism [BoNT/A(Hc)], plague (rF1-V), and SEB induced toxic-shock (STEBVax). A. Rhesus macaque skin immediately after vaccination (two sites, left to right): BoNT/A, rF1-V, rPA, and STEBVax. B. Rhesus macaque skin two months after vaccine administration. Marks are adjacent to injection sites. C. Skin sections (H&E stain) obtained from the vaccine delivery site exhibited epithelioid macrophages and multinucleated giant cells containing adjuvant (inset, green). Phalloidin staining of actin, red; Hoechst staining of DNA, blue. D. Macrophages at the vaccine delivery site exhibited high expression of MHC-II molecules (brown). Anti-MHC Class II immunohistochemistry (brown). E. Epithelioid macrophages (H&E stain) containing adjuvant (inset) were also present in the axillary lymph nodes of vaccinated animals. F. Vaccination did not significantly alter white blood cell counts of vaccinated animals (solid line) compared to control (dashed line). Mean cell counts ± SD of all animals studied.
Mentions: A simple mixture of the BoNT/A(Hc), F1-V, rPA and STEBVax as currently formulated resulted in formation of a precipitation and a significant change in pH of the solution (data not shown). Because of these apparent chemical incompatibilities we were not able to examine animals vaccinated with simple mixtures of the vaccines. The vaccines BoNT/A(Hc), F1-V, rPA and STEBVax were individually administered three times, 28 d apart, by injection into the shaved dermis of the upper arm or thigh of rhesus macaques using stainless steel microneedles that were the approximate diameter of a human hair, as previously reported [18-21]. The subject animals received doses of each vaccine that were independently optimized [11,13,17,19] and adsorbed to aluminum hydroxide adjuvant (AH). Control animals received i.d. injections of AH alone. The pattern of vaccinations consisted of an array of 100-μl injections separated by 2 cm, keeping each vaccine isolated from adjacent administrations (Fig. 1).

Bottom Line: Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. rulrich@bioanalysis.org.

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.

No MeSH data available.


Related in: MedlinePlus