Identification of adjuvants that enhance the therapeutic antibody response to host IgE

The currently available commercial human anthrax vaccine requires multiple injections for efficacy and has side effects due to its alum adjuvant. These factors limit its utility when immunizing exposed populations in emergent situations. We evaluated a novel mucosal adjuvant that consists of a nontoxic, water-in-oil nanoemulsion (NE). This material does not contain a proinflammatory component but penetrates mucosal surfaces to load antigens into dendritic cells. Mice and guinea pigs were intranasally immunized with recombinant Bacillus anthracis protective antigen (rPA) mixed in NE as an adjuvant. rPA-NE immunization was effective in inducing both serum anti-PA immunoglobulin G (IgG) and bronchial anti-PA IgA and IgG antibodies after either one or two mucosal administrations. Serum anti-PA IgG2a and IgG2b antibodies and PA-specific cytokine induction after immunization indicate a Th1-polarized immune response. rPA-NE immunization also produced high titers of lethal-toxin-neutralizing serum antibodies in both mice and guinea pigs. Guinea pigs nasally immunized with rPA-NE vaccine were protected against an intradermal challenge with ϳ1,000 times the 50% lethal dose (ϳ1,000؋ LD 50 ) of B. anthracis Ames strain spores (1.38 ؋ 10 3 spores), which killed control animals within 96 h. Nasal immunization also resulted in 70% and 40% survival rates against intranasal challenge with 10؋ LD 50 and 100؋ LD 50 (1.2 ؋ 10 6 and 1.2 ؋ 10 7 ) Ames strain spores. Our results indicate that NE can effectively adjuvant rPA for intranasal immunization. This potentially could lead to a needle-free anthrax vaccine requiring fewer doses and having fewer side effects than the currently available human vaccine.

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“…1B, inset). This is consistent with prior reports of alum adjuvant-based vaccines inducing a Th2 response (22,26).…”

Section: Resultssupporting

confidence: 93%

Mucosal Immunization with a Novel Nanoemulsion-Based Recombinant Anthrax Protective Antigen Vaccine Protects againstBacillus anthracisSpore Challenge

et al. 2007

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“…80 This very potent adjuvant system is comprised of a water-in-mineral oil emulsion with the emulsifier mannide monooleate. 107 Freund's complete adjuvant also contains heatkilled M. tuberculosis whereas IFA contains only the mineral oil emulsion and emulsifier. 29,63,107 Classically, proteinaceous antigens administered in CFA induce a very strong immune response, including cell-mediated responses, whereas immunogenic proteins administered intraperitoneally in IFA were thought to induce tolerance.…”

Section: Freund's Complete Adjuvant and Freund's Incomplete Adjuvantmentioning

confidence: 99%

“…107 Freund's complete adjuvant also contains heatkilled M. tuberculosis whereas IFA contains only the mineral oil emulsion and emulsifier. 29,63,107 Classically, proteinaceous antigens administered in CFA induce a very strong immune response, including cell-mediated responses, whereas immunogenic proteins administered intraperitoneally in IFA were thought to induce tolerance. 83,108 Advances in both knowledge of the immune system (induction of tolerance and Th2 responses) and methodology in measuring immune responses have shown that administration of antigens in IFA actually induces a Th2 response.…”

Section: Freund's Complete Adjuvant and Freund's Incomplete Adjuvantmentioning

confidence: 99%

“…108 Complete Freund's adjuvant is capable of inducing high antibody titers and long lasting T cell responses, but is so reactogenic that its use even in laboratory animals is discouraged. 107 The immune enhancing mechanisms of these adjuvants, the delayed release of antigen, slower antigen clearance, and targeting of the antigen to APCs is due to the mineral oil emulsion. 29 Variations on mineral oil emulsion vaccine adjuvants are marketed by Chiron and Norvarits as Montamide ISA-51 and ISA-720.…”

Section: Freund's Complete Adjuvant and Freund's Incomplete Adjuvantmentioning

confidence: 99%

“…While saponins have been used in veterinary vaccines for many years, a balance between potency and adverse reactions will need to be achieved for widespread acceptance in human vaccines. 64,107 A detoxified saponin derivative, QS-21, has exhibited marked decrease in toxicity while maintaining the strong immunoenhancing properties. 35,110 This adjuvant has been shown to induce a strong Th1 immune response (CTL, IL-2, IFN-g, and IgG2a) because of the lipid-cholesterol makeup.…”

Section: Mf59 Oil-emulsion Adjuvantsmentioning

confidence: 99%

See 2 more Smart Citations

Vaccine adjuvants: Current challenges and future approaches

Wilson-Welder

Torres

Kipper

et al. 2009

Journal of Pharmaceutical Sciences

243

178

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For humans, companion animals, and food producing animals, vaccination has been touted as the most successful medical intervention for the prevention of disease in the twentieth century. However, vaccination is not without problems. With the development of new and less reactogenic vaccine antigens, which take advantage of molecular recombinant technologies, also comes the need for more effective adjuvants that will facilitate the induction of adaptive immune responses. Furthermore, current vaccine adjuvants are successful at generating humoral or antibody mediated protection but many diseases currently plaguing humans and animals, such as tuberculosis and malaria, require cell mediated immunity for adequate protection. A comprehensive discussion is presented of current vaccine adjuvants, their effects on the induction of immune responses, and vaccine adjuvants that have shown promise in recent literature.

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Robo4 vaccines induce antibodies that retard tumor growth

et al. 2014

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Tumor endothelial specific expression of Robo4 in adults identifies this plasma membrane protein as an anti-cancer target for immunotherapeutic approaches, such as vaccination. In this report, we describe how vaccination against Robo4 inhibits angiogenesis and tumor growth. To break tolerance to the auto-antigen Robo4, mice were immunised with the extracellular domain of mouse Robo4, fused to the Fc domain of human immunoglobulin within an adjuvant. Vaccinated mice show a strong antibody response to Robo4, with no objectively detectable adverse effects on health. Robo4 vaccinated mice showed impaired fibrovascular invasion and angiogenesis in a rodent sponge implantation assay, as well as a reduced growth of implanted syngeneic Lewis lung carcinoma. The anti-tumor effect of Robo4 vaccination was present in CD8 deficient mice but absent in B cell or IgG1 knockout mice, suggesting antibody dependent cell mediated cytotoxicity as the anti-vascular/anti-tumor mechanism. Finally, we show that an adjuvant free soluble Robo4-carrier conjugate can retard tumor growth in carrier primed mice. These results point to appropriate Robo4 conjugates as potential anti-angiogenic vaccines for cancer patients.

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Identification of adjuvants that enhance the therapeutic antibody response to host IgE

Cited by 25 publications

References 18 publications

Mucosal Immunization with a Novel Nanoemulsion-Based Recombinant Anthrax Protective Antigen Vaccine Protects againstBacillus anthracisSpore Challenge

Mucosal Immunization with a Novel Nanoemulsion-Based Recombinant Anthrax Protective Antigen Vaccine Protects againstBacillus anthracisSpore Challenge

Vaccine adjuvants: Current challenges and future approaches

Robo4 vaccines induce antibodies that retard tumor growth

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