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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

Potent neutralizing antibody responses of rhesus macaques receiving concurrent intradermal administrations of four independent vaccines. A. Neutralizing antibody titers for animals in: A. botulinum neurotoxin type A challenge group. B. anthrax challenge group. C. SEB challenge group. Individual animals vaccinated with antigens plus AH, Vaccinated 1–6; injected with AH only, Control 1–2. All disease challenges occurred one month after the final vaccination. Geometric mean titers, based on triplicate determinations.
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Figure 3: Potent neutralizing antibody responses of rhesus macaques receiving concurrent intradermal administrations of four independent vaccines. A. Neutralizing antibody titers for animals in: A. botulinum neurotoxin type A challenge group. B. anthrax challenge group. C. SEB challenge group. Individual animals vaccinated with antigens plus AH, Vaccinated 1–6; injected with AH only, Control 1–2. All disease challenges occurred one month after the final vaccination. Geometric mean titers, based on triplicate determinations.

Mentions: Standard assays were previously established for determining the level of antibodies present in sera that protect the vaccinated host from SEB-toxic shock, botulism, and anthrax. These neutralizing antibody assays provided an additional parameter for predicting the outcome of exposure to each agent of disease. The BoNT/A neutralizing antibody titers were determined as the reciprocal of the serum dilution that protected 50% of the mice from challenge with 10 LD50 of toxin. Serum from vaccinated primates protected CD-1 mice challenged with BoNT/A (Fig. 3A); serum from control animals was not protective. Antibodies that neutralized B. anthracis were present in all vaccinated animals, but not in controls, as determined by measuring inhibition of J774 cell lysis after exposure to anthrax lethal toxin (Fig. 3B). Additionally, serum from vaccinated animals prevented SEB-induced proliferation of human peripheral blood mononuclear cells after addition of the toxin to culture (Fig. 3C). We could not determine the titers of neutralizing antibody against plague because there were no previously validated assays available for the rhesus monkey that permitted correlation of antibody titer with protection from disease.


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)

Potent neutralizing antibody responses of rhesus macaques receiving concurrent intradermal administrations of four independent vaccines. A. Neutralizing antibody titers for animals in: A. botulinum neurotoxin type A challenge group. B. anthrax challenge group. C. SEB challenge group. Individual animals vaccinated with antigens plus AH, Vaccinated 1–6; injected with AH only, Control 1–2. All disease challenges occurred one month after the final vaccination. Geometric mean titers, based on triplicate determinations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Potent neutralizing antibody responses of rhesus macaques receiving concurrent intradermal administrations of four independent vaccines. A. Neutralizing antibody titers for animals in: A. botulinum neurotoxin type A challenge group. B. anthrax challenge group. C. SEB challenge group. Individual animals vaccinated with antigens plus AH, Vaccinated 1–6; injected with AH only, Control 1–2. All disease challenges occurred one month after the final vaccination. Geometric mean titers, based on triplicate determinations.
Mentions: Standard assays were previously established for determining the level of antibodies present in sera that protect the vaccinated host from SEB-toxic shock, botulism, and anthrax. These neutralizing antibody assays provided an additional parameter for predicting the outcome of exposure to each agent of disease. The BoNT/A neutralizing antibody titers were determined as the reciprocal of the serum dilution that protected 50% of the mice from challenge with 10 LD50 of toxin. Serum from vaccinated primates protected CD-1 mice challenged with BoNT/A (Fig. 3A); serum from control animals was not protective. Antibodies that neutralized B. anthracis were present in all vaccinated animals, but not in controls, as determined by measuring inhibition of J774 cell lysis after exposure to anthrax lethal toxin (Fig. 3B). Additionally, serum from vaccinated animals prevented SEB-induced proliferation of human peripheral blood mononuclear cells after addition of the toxin to culture (Fig. 3C). We could not determine the titers of neutralizing antibody against plague because there were no previously validated assays available for the rhesus monkey that permitted correlation of antibody titer with protection from disease.

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