Impact of the saponin adjuvant QS-21 and aluminium hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi

Ma, Ji; Bulger, Patrice A.; Davis, Deborah vR.; Perilli-Palmer, Barbara; Bedore, Deborah A.; Kensil, Charlotte R.; Young, Eli M.; Hung, Chung-Ho; Seals, Jonathan R.; Pavia, Charles S.; Coughlin, Richard T.

doi:10.1016/0264-410x(94)90036-1

Cited by 38 publications

(22 citation statements)

References 42 publications

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“…For example, in the mouse, IgG2a and IgG3 are opsonic and participate in complement-mediated killing, whereas IgG1 does not activate complement by the classical pathway but is effective in neutralization of exotoxins and extracellular bacteria. Both IgG1 and IgG2a Ab responses were consistently reported after parenteral immunization with protein or polysaccharide Ags given with QS-21 (11,12,33,34). More variable results were reported for IgG2b Abs with either their presence (12) or absence after parenteral QS-21 delivery.…”

Section: Discussionmentioning

confidence: 96%

“…Both IgG1 and IgG2a Ab responses were consistently reported after parenteral immunization with protein or polysaccharide Ags given with QS-21 (11,12,33,34). More variable results were reported for IgG2b Abs with either their presence (12) or absence after parenteral QS-21 delivery. Because no IgG2a Abs are induced by low p.o.…”

Section: Discussionmentioning

confidence: 96%

“…Approximately 10-fold higher levels of CT are required as oral adjuvant when compared with the parenteral or nasal route (3,8,24,29). Studies by others have shown that QS-21 doses of 10 -20 g were optimal for enhancing immune responses to parenteral vaccines in animal models (10,12,13,15,34). Interestingly, oral QS-21 enhanced systemic immunity to the coadministered Ag with doses only 1.5-to 3-fold higher than those required for systemic immunization.…”

Section: Discussionmentioning

confidence: 99%

“…This molecule promotes both humoral and cell-mediated immunity when added to systemic vaccine formulations (7,(11)(12)(13). QS-21 is currently under clinical evaluation for various parenterally administered vaccines (14).…”

mentioning

confidence: 99%

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Oral QS-21 Requires Early IL-4 Help for Induction of Mucosal and Systemic Immunity

Boyaka

Marinaro²,

Jackson

et al. 2001

The Journal of Immunology

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The highly purified saponin derivative, QS-21, from the Quillaja saponaria Molina tree has been proved to be safe for parenteral administration and represents a potential alternative to bacterial enterotoxin derivatives as a mucosal adjuvant. Here we report that p.o. administration of QS-21 with the vaccine protein tetanus toxoid elicited strong serum IgM and IgG Ab responses, which were only slightly enhanced by further oral immunization. The IgG Ab subclass responses were predominantly IgG1 followed by IgG2b for the 50-μg p.o. dose of QS-21, whereas the 250-μg p.o. dose also induced IgG2a and IgG3 Abs. Low oral QS-21 doses induced transient IgE Ab responses 7 days after the primary immunization, whereas no IgE Ab responses were seen in mice given the higher QS-21 dose. Further, low but not high p.o. QS-21 doses triggered Ag-specific secretory IgA (S-IgA) Ab responses. Th cell responses showed higher IFN-γ (Th1-type) and lower IL-5, IL-6, and IL-10 (Th2-type) secretion after the high QS-21 p.o. dose than after low doses. Interestingly, the mucosal adjuvant activity of low oral QS-21 doses was diminished in IL-4−/− mice, suggesting a role for this cytokine in the initiation of mucosal immunity by oral QS-21. In summary, our results show that oral QS-21 enhances immunity to coadministered Ag and that different doses of QS-21 lead to distinct patterns of cytokine and serum Ab responses. We also show that an early IL-4 response is required for the induction of mucosal immunity by oral QS-21 as adjuvant.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Oral QS-21 Requires Early IL-4 Help for Induction of Mucosal and Systemic Immunity

Boyaka

Marinaro²,

Jackson

et al. 2001

The Journal of Immunology

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“…Several reports, however, have indicated that OspB is present on the surface of B. burgdorferi within unfed ticks (2,17,23). Certain OspB antibodies, either as whole immunoglobulin G (IgG) or as Fab fragments, can be bactericidal in vitro, and studies have demonstrated that vaccination with OspB can protect mice from B. burgdorferi infection (5,7,13,14). Because OspB is located on the surface of B. burgdorferi, expressed by spirochetes within ticks, and encoded on a bicistronic operon with ospA, we examined the role of OspB in B. burgdorferi-I.…”

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OspB Antibody Prevents Borrelia burgdorferi Colonization of Ixodes scapularis

et al. 2004

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Borrelia burgdorferi outer surface protein OspB is expressed by spirochetes in the Ixodes scapularis gut. ospB is transcribed from a bicistronic operon with ospA, a known spirochete adhesion gene in the tick gut. Here we examine whether OspB also has a specific function in ticks. OspB specifically binds to a protein or protein complex within the tick gut. We also assessed whether selected nonborreliacidal OspB antibodies or F(ab) 2 fragments interfere with B. burgdorferi-tick attachment in vivo. We examined engorged ticks that fed on B. burgdorferi N40-infected scid mice that had been treated with OspB F(ab) 2 fragments. Control F(ab) 2 fragments did not interfere with B. burgdorferi colonization of the tick gut, whereas OspB F(ab) 2 fragments significantly inhibited the attachment of spirochetes to the tick gut. These studies show that nonbactericidal OspB antibodies interfere with B. burgdorferi colonization of I. scapularis, highlighting a specific role for OspB in spirochetearthropod interactions and suggesting new antibody-mediated strategies for interfering with B. burgdorferi transmission.

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Increased Expression of B-Lymphocyte Chemoattractant, but Not Pro-Inflammatory Cytokines, in Muscle Tissue in Rhesus Chronic Lyme Borreliosis

et al. 2002

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Impact of the saponin adjuvant QS-21 and aluminium hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi

Cited by 38 publications

References 42 publications

Oral QS-21 Requires Early IL-4 Help for Induction of Mucosal and Systemic Immunity

Oral QS-21 Requires Early IL-4 Help for Induction of Mucosal and Systemic Immunity

OspB Antibody Prevents Borrelia burgdorferi Colonization of Ixodes scapularis

Increased Expression of B-Lymphocyte Chemoattractant, but Not Pro-Inflammatory Cytokines, in Muscle Tissue in Rhesus Chronic Lyme Borreliosis

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