Low-dose intraperitoneal Freund's adjuvant: Toxicity and immunogenicity in mice using an immunogen targeting amyloid-β peptide

Oscherwitz, Jon; Hankenson, F. Claire; Yu, Fang; Cease, Kemp B.

doi:10.1016/j.vaccine.2005.10.046

Cited by 34 publications

(33 citation statements)

References 22 publications

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“…The observed increase was attributed to adjuvant-induced oedema and/or inflammation, which may promote water retention [44]. Indeed, these investigators demonstrated that IFA and CFA were equally effective, and more so than ALU, in generating a mouse weight increase.…”

Section: Discussionmentioning

confidence: 98%

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice

Favoino

Favia

Digiglio

et al. 2013

Clinical and Experimental Immunology

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SummaryThe safety of four different adjuvants was assessed in lupus-prone New Zealand black/New Zealand white ( Mean mouse weight at week 18 was lower in the ALU group than the IFA (Tukey's HSD post-test P = 0·04), CFA (P = 0·01) and SQU (P < 0·0001) groups, while the mean weight in the SQU group was higher than in the IFA (P = 0·009), CFA (P = 0·013) and UNT (P = 0·005) groups. The ALU group weight decreased by almost half between weeks 29 and 31, indicating some toxic effect of ALU in the late post-immunization period. Thus, SQU was the least toxic adjuvant as it did not (i) accelerate proteinuria onset compared to IFA; (ii) induce toxicity compared to ALU or (iii) elicit anti-RNP/Sm autoantibody, as occurred in the CFA group.

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Section: Discussionmentioning

confidence: 98%

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice

Favoino

Favia

Digiglio

et al. 2013

Clinical and Experimental Immunology

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“…Two recombinant proteins were used for assessing immunity specific for the peptide comprising aa 305 to 319 (305-319 peptide) of PA by an enzyme-linked immunosorbent assay (ELISA). Both recombinant proteins were molecularly constructed, expressed, and purified essentially as previously described (35). The recombinants display two tandemly repeated copies of either aa 299 to 327 (single-letter code, HTSEVHGNAEVHASFFDIGGSVSAGFSNS) or aa 305 to 319 (single-letter code, GNAEVHASFFDIGGS) of PA linked to maltose binding protein.…”

Section: Methodsmentioning

confidence: 99%

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

Oscherwitz

Jacobs

et al. 2009

Infect Immun

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Current evidence suggests that protective antigen (PA)-based anthrax vaccines may elicit a narrow neutralizing antibody repertoire, and this may represent a vulnerability with PA-based vaccines. In an effort to identify neutralizing specificities which may complement those prevalent in PA antiserum, we evaluated whether sequences within the 2␤2-2␤3 loop of PA, which are apparent in the crystal structure of heptameric but not monomeric PA, might represent a target for an epitope-specific vaccine for anthrax and, further, whether antibodies to these sequences are induced in rabbits immunized with monomeric PA. We evaluated the immunogenicity in rabbits of a multiple antigenic peptide (MAP) displaying copies of amino acids (aa) 305 to 319 of this region. Overall, four out of six rabbits vaccinated with the MAP peptide in Freund's adjuvant developed high-titer, high-avidity antibody responses which cross-reacted with the immobilized peptide sequence comprising aa 305 to 319 and with PA, as determined by an enzyme-linked immunosorbent assay, and which displayed potent and durable neutralization of lethal toxin (LeTx) in vitro, with peak titers which were 452%, 100%, 67%, and 41% of the peak neutralization titers observed in positive-control rabbits immunized with PA. Importantly, analysis of sera from multiple cohorts of rabbits with high-titer immunity to PA demonstrated a virtual absence of this potent antibody specificity, and work by others suggests that this specificity may be present at only low levels in primate PA antiserum. These results highlight the potential importance of this immunologically cryptic neutralizing epitope from PA as a target for alternative and adjunctive vaccines for anthrax.

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“…The humoral immunogenicity enhancement of CFA is more effective than aluminum salts for a 42-amino acid amyloid-beta peptide antigen [124] and for cystein proteinase antigen in mice [94]. However, severe toxicities have been observed even at a reduced dose, such as weight loss, leukocytosis, abdominal adhesions, granulomatous peritonitis, and disrupted hyalimized myofibers in mice [94,124]. Other animal toxicities include skin lesions in rats and arthritis in dogs [66].…”

Section: Emulsionsmentioning

confidence: 99%

“…With less toxicities, this adjuvant is less potent in mice [124]. In addition, the water in oil emulsions were highly viscous and not stable [123].…”

Section: Emulsionsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Low-dose intraperitoneal Freund's adjuvant: Toxicity and immunogenicity in mice using an immunogen targeting amyloid-β peptide

Cited by 34 publications

References 22 publications

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

Selection of Adjuvants for Enhanced Vaccine Potency

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