scholarly journals Nanodiamonds in Oil Emulsions as Effective Vaccine Adjuvants and Antitumor Therapeutic Agents

2022 ◽  
Author(s):  
Hsin-Hung Lin ◽  
Chih-Yen Wang ◽  
Feng-Jen Hsieh ◽  
Fang-Zhen Liao ◽  
Yu-Kai Su ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Antibody Production ◽  
High Efficiency ◽  
Vaccine Adjuvant ◽  
Effective Vaccine ◽  
Vaccine Adjuvants ◽  
Igg Antibody ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
New Formulation

Abstract Background Composed of mineral oil and mycobacteria pathogens, complete Freund’s adjuvant (CFA) is one of the most commonly used adjuvants for antibody production and scientific research due to its high efficiency. However, the dead mycobacteria in CFA can cause many allergic reactions. We propose here a new formulation based on the use of nanodiamonds (NDs) as biocompatible non-allergic additives in incomplete Freund’s adjuvant (IFA) to avoid these adverse effects. Methods Chicken egg ovalbumin (OVA) was used as the antigens and 100-nm NDs after purification by air oxidation and strong oxidative acid washes were used as the additives. Levels of OVA-specific IgG antibody in mouse sera were measured by using enzyme-linked immunosorbent assays (ELISA) after the second and third immunizations of healthy mice with OVA and OVA/ND in IFA or CFA. Abilities of the OVA/ND/IFA vaccination to inhibit the tumor growth of mice inoculated with EL4 cells or OVA-expressing E.G7 cells were examined over 1 month. Results The new formulation worked well as a potent vaccine adjuvant, which could boost the immune responses and reduce the consumption of antigens in producing antibodies of interest in model animals like mice. Additionally, the composites showed distinct therapeutic activities, as proven by the OVA/ND/IFA treatment that effectively inhibited the tumor progression of E.G7-inoculated mice, allowing the animals to survive over 35 days post tumor-cell challenges. About 0.2% of the injected ND particles were found in mouse spleens on day 24 after vaccination of the E.G7-inoculated mice with OVA/ND/IFA. Conclusions The multiple functionality of ND makes it useful as an active and trackable component of a vaccine adjuvant not only to enhance antibody production but also to suppress tumor growth in vivo. The ND-based new formulation can be developed into single-dose vaccines with promising potential for real-world applications.

Nanodiamonds in Oil Emulsions as Effective Vaccine Adjuvants and Antitumor Therapeutic Agents

2021 ◽  
Author(s):  
Hsin-Hung Lin ◽  
Chih-Yen Wang ◽  
Feng-Jen Hsieh ◽  
Fang-Zhen Liao ◽  
Yu-Kai Su ◽  
...  
Keyword(s):  
Antibody Production ◽  
High Efficiency ◽  
Effective Vaccine ◽  
Vaccine Adjuvants ◽  
Immunological Responses ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Oil Emulsions ◽  
New Formulation ◽  
Therapeutic Activities

Abstract Background Vaccination is an effective tool to elicit immunological responses that mediate the protection from infection or disease. Composed of mineral oil and mycobacteria pathogens, complete Freund’s adjuvant (CFA) is one of the most commonly employed adjuvants for antibody production and vaccination due to its high efficiency. However, the dead mycobacteria in CFA can cause many allergic reactions. To avoid these adverse effects, we propose here a new formulation based on the use of nanodiamonds (NDs) as biocompatible non-allergic additives in incomplete Freund’s adjuvant (IFA) instead. ResultsTested with chicken egg ovalbumin (OVA) in mouse models, the new formulation with 100-nm NDs was found to serve well as a safe and potent vaccine adjuvant that significantly enhanced the immune responses and reduced the consumption of antigens in producing the antibodies of interest. Additionally, the composites showed distinct therapeutic activities, as proven by the OVA/ND/IFA treatment which effectively inhibited the tumor progression of OVA-expressing E.G7 cells inoculated in mice and allowed the animals to survive up to 35 days post tumor-cell challenges. ConclusionsThe dual functionality of ND/IFA makes it useful as adjuvants not only to increase antibody production but also to create single-dose vaccines.

scholarly journals Archaeosome Vaccine Adjuvants Induce Strong Humoral, Cell-Mediated, and Memory Responses: Comparison to Conventional Liposomes and Alum

2000 ◽  
Vol 68 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Lakshmi Krishnan ◽  
Chantal J. Dicaire ◽  
Girishchandra B. Patel ◽  
G. Dennis Sprott
Keyword(s):  
Immune Responses ◽  
Lipid Vesicles ◽  
Interleukin 4 ◽  
Molar Ratio ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Vaccine Adjuvants ◽  
Strong Response ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

ABSTRACT Ether glycerolipids extracted from various archaeobacteria were formulated into liposomes (archaeosomes) possessing strong adjuvant properties. Mice of varying genetic backgrounds, immunized by different parenteral routes with bovine serum albumin (BSA) entrapped in archaeosomes (∼200-nm vesicles), demonstrated markedly enhanced serum anti-BSA antibody titers. These titers were often comparable to those achieved with Freund's adjuvant and considerably more than those with alum or conventional liposomes (phosphatidylcholine-phosphatidylglycerol-cholesterol, 1.8:0.2:1.5 molar ratio). Furthermore, antigen-specific immunoglobulin G1 (IgG1), IgG2a, and IgG2b isotype antibodies were all induced. Association of BSA with the lipid vesicles was required for induction of a strong response, and >80% of the protein was internalized within most archaeosome types, suggesting efficient release of antigen in vivo. Encapsulation of ovalbumin and hen egg lysozyme within archaeosomes showed similar immune responses. Antigen-archaeosome immunizations also induced a strong cell-mediated immune response: antigen-dependent proliferation and substantial production of cytokines gamma interferon (Th1) and interleukin-4 (IL-4) (Th2) by spleen cells in vitro. In contrast, conventional liposomes induced little cell-mediated immunity, whereas alum stimulated only an IL-4 response. In contrast to alum and Freund's adjuvant, archaeosomes composed of Thermoplasma acidophilum lipids evoked a dramatic memory antibody response to the encapsulated protein (at ∼300 days) after only two initial immunizations (days 0 and 14). This correlated with increased antigen-specific cell cycling of CD4+ T cells: increase in synthetic (S) and mitotic (G2/M) and decrease in resting (G1) phases. Thus, archaeosomes may be potent vaccine carriers capable of facilitating strong primary and memory humoral, and cell-mediated immune responses to the entrapped antigen.

scholarly journals CYT-0853, a Novel RAD51 Inhibitor, Modulates Immunoregulatory B-Lymphocytes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2330-2330
Author(s):  
Tamar Aprahamian ◽  
ED Keniston ◽  
Jane Branca ◽  
Muneer G Hasham ◽  
Melinda Day ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Antibody Production ◽  
Cytidine Deaminase ◽  
Autoreactive B Cells ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Activation Induced Cytidine Deaminase (AICDA/AID) is a DNA-directed cytidine deaminase that is normally only expressed in activated B-cells to promote somatic hypermutations and immunoglobulin class switching. In cancer cells, AID causes significant genotoxic stress through DNA replication fork damage, creating a dependency upon the homologous recombination repair factor, RAD51, for survival. We have demonstrated anti-cancer activity through disruption of this axis in multiple preclinical lymphoid cancer models. Autoreactive B cells depend on RAD51 for survival and are chronically auto-stimulated and therefore continually re-express AID. It has been shown that ectopic expression of AID in autoreactive B-cells causes genome-wide DNA damage (similar to cancers). Given the role of autoreactive B cells and autoantibodies in autoimmune disorders, we hypothesize that immunomodulation of B cells via the RAD51/AID axis will remediate inflammatory disease processes. Our previous data suggests that RAD51 modulation enhances the CD73+ B cell population and reduces antibody diversity in T1D mice, indicating precise effects on AID-mediated antibody diversification. CYT-0853 is a novel RAD51 inhibitor that sensitizes cells to AID activity. Here, we assessed the in vivo effect of CYT-0853 on primary B cells and antibody production. Wild-type C57BL/6 mice were treated with 40mg/kg CYT-0853 or vehicle for five weeks. One-week post-treatment start, mice were immunized with DNP-KLH antigen mixed with Complete Freund's Adjuvant. A second booster with DNP-KLH antigen mixed with Incomplete Freund's Adjuvant was administered two weeks later. At termination, blood, spleen, and bone marrow was collected for analysis by flow cytometry. Surface expression of CD45, CD19, IgM, and IgG1 was assessed to determine white blood cell count, B cells, and pre- and post-class switch recombination (CSR), respectively. While no significant changes to B cell populations were observed in bone marrow or spleen, we demonstrate that CYT-0853 significantly decreases the median number of circulating CD45+ and IgG1 (post-CSR) B cells (61.8% vs. 31.6% and 8.7% vs. 4.4%, respectively). In addition, we observed a modest, significant increase in the amount of IgM+ (pre-CSR) B cells. These results were complemented by an associated overall significant decrease in circulating IgM levels. Of note, no adverse effects were observed in these mice over this treatment period. Based on these data and the role of B cells not only in antibody production, but also as antigen-presenting cells in multiple sclerosis, we tested our molecule in the myelin oligodendrocyte glycoprotein35-55-experimental autoimmune encephalomyelitis model of multiple sclerosis. Prophylactic treatment using 40mg/kg CYT-0853 did not affect disease activity or circulating cytokine production, however we observed a significant decrease in the spleen. Based on these results, further exploration is warranted to harness the power of CYT-0853 on the AID/RAD51 axis. This specific targeting may elicit beneficial therapeutic changes to B-lymphocyte populations and provide a novel immunomodulatory target to treat immunity and inflammation. Taken together, these data provide a foundation for continued preclinical development of CYT-0853 with applicability towards autoimmune diseases. Disclosures Aprahamian: Cyteir Therapeutics: Consultancy. Day:Cyteir Therapeutics: Employment. Mills:Cyteir Therapeutics: Employment, Equity Ownership.

scholarly journals Cell Recruitment and Cytokines in Skin Mice Sensitized with the Vaccine Adjuvants: Saponin, Incomplete Freund’s Adjuvant, and Monophosphoryl Lipid A

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40745 ◽  
Author(s):  
Juliana Vitoriano-Souza ◽  
Nádia das Dores Moreira ◽  
Andréa Teixeira-Carvalho ◽  
Cláudia Martins Carneiro ◽  
Fernando Augusto Mathias Siqueira ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Adjuvants ◽  
Cell Recruitment ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

scholarly journals GENETIC CONTROL OF THE IMMUNE RESPONSE

1972 ◽  
Vol 135 (1) ◽  
pp. 126-135 ◽  
Author(s):  
Graham F. Mitchell ◽  
F. Carl Grumet ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
Cell Interaction ◽  
Primary Response ◽  
High Response ◽  
High Responder ◽  
Igg Antibody ◽  
Low Responder ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Synthetic Polypeptide

The effect of thymectomy on the genetically controlled murine immune response-1 (Ir-1) to the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] was studied with both aqueous and adjuvant immunization regimens. Adult thymectomy (combined with irradiation and bone marrow transfusion) did not affect the aqueous antigen-induced (IgM) primary response of either high or low responder mice, but did ablate the (IgG) secondary or tertiary response, a response which is restricted to the high responder strains. Adult thymectomy also blocked the normal high response to (T,G)-A--L in Freund's adjuvant in high responder mice and the high response to methylated bovine serum albumin (MBSA)-(T,G)-A--L in low responder mice. Neonatal thymectomy was also effective in blocking the response to (T, G)-A--L in Freund's adjuvant in high responder mice. These data are consistent with the concept that the Ir-1 gene effect is mediated via thymus cell interaction with antigen and with "B"-cells during the time of induction of IgG antibody formation.

scholarly journals TERMINATION OF ACQUIRED IMMUNOLOGICAL TOLERANCE TO PROTEIN ANTIGENS FOLLOWING IMMUNIZATION WITH ALTERED PROTEIN ANTIGENS

1962 ◽  
Vol 116 (6) ◽  
pp. 913-928 ◽  
Author(s):  
William O. Weigle
Keyword(s):  
Antibody Production ◽  
Clonal Selection ◽  
Immunological Tolerance ◽  
The Other ◽  
Protein Antigens ◽  
Clonal Selection Theory ◽  
Altered Protein ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Tolerant State

Acquired tolerance to BSA in rabbits was terminated following the injection of certain preparations of altered BSA. Injections of Freund's adjuvant containing BSA complexed to anti-BSA, heat-denatured BSA, acetyl-BSA, picryl-BSA, or arsanil-BSA failed to terminate the tolerant state. Except in an occasional tolerant rabbit, injections of these preparations failed to cause the production of precipitating antibody to the altered preparation. Similar results were obtained following injections of alum-precipitated preparations of pepsin-degraded BSA, acetyl-BSA, and picryl-BSA. Injections of Freund's adjuvant containing sulfanil-BSA terminated the tolerant state, but only small amounts of non-precipitating anti-BSA were produced. Injections of Freund's adjuvant containing picryl-acetyl-BSA terminated the tolerant state in two of six rabbits, but again, only small amounts of non-precipitating anti-BSA were produced. Injections of an alum-precipitated preparation of picryl-acetyl-BSA failed to terminate the tolerant state. On the other hand, injections of Freund's adjuvant containing arsanil-sulfanil-BSA terminated the tolerant state in eleven of eleven rabbits and caused the production of precipitating anti-BSA in all nine of the rabbits tested. The tolerant state was terminated also in six of six rabbits injected with an alum-precipitated preparation of arsanil-sulfanil-BSA. Only one of these rabbits produced precipitating anti-BSA. In addition, the injection of BGG-tolerant rabbits with arsanil-BGG, sulfanil-BGG, or arsanil-sulfanil-BGG terminated the tolerant state. These results were discussed in relation to both the clonal selection theory of antibody production and autoimmunity.

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