Endotoxin-minimized HIV-1 p24 fused to murine hsp70 activates dendritic cells, facilitates endocytosis and p24-specific Th1 response in mice

Křupka, Michal; Zachová, Kateřina; Cahlikova, Romana; Vrbková, Jana; Novak, Zuzana; Šebela, Marek; Weigl, E.; Raška, Milan

doi:10.1016/j.imlet.2015.05.010

Cited by 27 publications

(19 citation statements)

References 56 publications

(77 reference statements)

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“…Pooled sera from mice in each group were used for ELISA analysis of OspC-specific antibodies. Control sera were obtained from mice immunized by recombinant His-tagged p24-Hsp70 without adjuvants [ 26 ]. ELISA plates were coated with 0.1 μg of non-tagged rOspC, incubated with serially diluted pooled sera obtained 14 days after second immunization and developed with HRP-conjugated anti-mouse A ) IgG+IgM+IgA (IgP), B ) IgG1, and C ) IgG2a, developed with orthophenylene diamine.…”

Section: Resultsmentioning

confidence: 99%

“…The composition of particular formulations is specified ( Table 1 ) . As a naïve control, we used sera from mice immunized with recombinant His-tag p24-Hsp70 protein [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…For all ELISA, rOspC was devoid of all tags using recombinant enterokinase as described recently [ 26 ]. ELISA assays were performed as described [ 26 ]. In brief, ELISA wells were coated with 100 ng/well of non-tag rOspC.…”

Section: Methodsmentioning

confidence: 99%

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The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

et al. 2016

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Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag) OspC (rOspC) could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a) with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b) with free rOspC and Montanide PET GEL A; (c) with free rOspC and alum; or (d) with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.

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Section: Resultsmentioning

confidence: 99%

“…The composition of particular formulations is specified ( Table 1 ) . As a naïve control, we used sera from mice immunized with recombinant His-tag p24-Hsp70 protein [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

et al. 2016

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“…[17][18][19] Other examples tested in preclinical studies include Ag473, a TLR2 ligand fused to dengue virus envelope protein E3; 66 HSP70 fused to HIV-1 p24 protein; 44 and the type III repeat extra domain A from fibronectin (EDA) as TLR4 ligand fused to chicken ovalbumin (OVA) epitope. 45,53,66,67 All the above examples will be discussed in the following paragraphs. Trumenba ® is the first vaccine approved by the FDA to protect against invasive disease caused by Neisseria meningitidis serogroup B (NMB) in individuals aged 10 to 25.…”

Section: Role Of Toll-like Receptor Ligands As Covalently Attached Immentioning

confidence: 99%

Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands

Moyle

2017

Bioconjugate Chem.

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Traditional vaccines derived from attenuated or inactivated pathogens are effective at inducing antibody-based protective immune responses but tend to be highly reactogenic, causing notable adverse effects. Vaccines with superior safety profiles can be produced by subunit approaches, utilizing molecularly defined antigens (e.g., proteins and polysaccharides). These antigens, however, often elicit poor immunological responses, necessitating the use of adjuvants. Immunostimulatory adjuvants have the capacity to activate antigen presenting cells directly through specific receptors (e.g., Toll-like receptors (TLRs)), resulting in enhanced presentation of antigens as well as the secretion of proinflammatory chemokines and cytokines. Consequently, innate immune responses are amplified and adaptive immunity is generated. Recently, site-specific conjugation of such immunostimulatory adjuvants (e.g., TLR ligands) onto defined antigens has shown superior efficacy over unconjugated mixtures, suggesting that the development of chemically characterized immunostimulatory adjuvants and optimized approaches for their conjugation with antigens may provide a better opportunity for the development of potent, novel vaccines. This review briefly summarizes various TLR agonists utilized as immunostimulatory adjuvants and focuses on the development of techniques (e.g., recombinant, synthetic, and semisynthetic) for generating adjuvant-antigen fusion vaccines incorporating peptide or protein antigens.

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“…These proteins have certain immunomodulatory effects and can be used as vaccine adjuvants. An adjuvant codelivery system produced by the fusion of HSP-70 and HIV-1 p24 proteins stimulates stronger cellular immunity than a simple antigen-adjuvant mix [110]. Using the gene fusion method, mouse Hsp70 has been fused with tumor antigen MAGE-A1 to obtain an adjuvant-antigen codelivery vaccine.…”

Section: Covalent Coupling Of Protein Adjuvants To Antigens By Gene Fmentioning

confidence: 99%

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

Wang

2020

Vaccines

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Traditional aluminum adjuvants can trigger strong humoral immunity but weak cellular immunity, limiting their application in some vaccines. Currently, various immunomodulators and delivery carriers are used as adjuvants, and the mechanisms of action of some of these adjuvants are clear. However, customizing targets of adjuvant action (cellular or humoral immunity) and action intensity (enhancement or inhibition) according to different antigens selected is time-consuming. Here, we review the adjuvant effects of some delivery systems and immune stimulants. In addition, to improve the safety, effectiveness, and accessibility of adjuvants, new trends in adjuvant development and their modification strategies are discussed.

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Endotoxin-minimized HIV-1 p24 fused to murine hsp70 activates dendritic cells, facilitates endocytosis and p24-specific Th1 response in mice

Cited by 27 publications

References 56 publications

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

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