14 research outputs found
Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
CAPRISA, 2017.Abstract available in pdf
Arylazoimidazole complexes of lead(II)-halide and their photochromism
418-426Lead(II) complexes of 1-alkyl-2-(arylazo)imidazole (Raai-CnH2n+1), [Pb(Raai-CnH2n+1)X2] (X = Cl, Br, I; and Raai-CnH2n+1, R = H, Me and n = 4, 6, 8) have been characterized by UV-vis, IR and 1H-NMR spectroscopy. The coordinated Raai-CnH2n+1 in the complexes undergoes E-to-Z (trans-to-cis) isomerisation about the –N=N– group upon being irradiated with UV light in DMF solution. The rate and quantum yields of E-to-Z photoisomerisation (φE→Z) of the complexes are poorer than the respective free ligand response and are also affected by the nature of halide present (Cl-, Br- and I-). Variation in physicochemical parameters may be correlated with the effective mass of the photochrome. The rate of isomerisation follows the sequence: [Pb(Raai-CnH2n+1)Cl2] nH2n+1)Br2] nH2n+1)I2]. The Z-to-E isomerisation has been carried out at varying temperatures (298–308 K) to determine the activation energy of Z-to-E (cis-to-trans) isomerisation (Ea: 47.09–63.42 kJ mol-1) and the entropy of activation (S : 166.52 to –109.0 J mol-1 K-1) which is a large negative in the complexes. Theoretical calculation supports cleavage of Pb(II)-N(azo) bond followed by the –N=N– rotation in a three-coordinated symmetry rather than the four-coordinated symmetry
Tobacco Mosaic Virus as a New Carrier for Tumor Associated Carbohydrate Antigens
Tumor associated carbohydrate antigens (TACAs) are being actively studied as targets for anti-tumor vaccine development. One serious challenge was the low immunogenecity of these antigens. Herein, we report the results on using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide-alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities towards Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier
Entanglement of cation ordering and manipulation of the magnetic properties through a temperature-controlled topotactic interface reaction in nanocomposite perovskite oxides
International audienceSchematic view of cation ordering across the interface of the grain boundary of two different perovskites via controlled thermal treatment. Such ordering is sensitive to the magnetic property
Tobacco Mosaic Virus as a New Carrier for Tumor Associated Carbohydrate Antigens
Tumor-associated
carbohydrate
antigens (TACAs) are being actively studied as targets for antitumor
vaccine development. One serious challenge was the low immunogenecity
of these antigens. Herein, we report the results of using the tobacco
mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic
TACA, the monomeric Tn antigen. The copperÂ(I) catalyzed azide–alkyne
cycloaddition reaction was highly efficient in covalently linking
Tn onto the TMV capsid without resorting to a large excess of the
Tn antigen. The location of Tn attachment turned out to be important.
Tn introduced at the N terminus of TMV was immunosilent, while that
attached to tyrosine 139 elicited strong immune responses. Both Tn
specific IgG and IgM antibodies were generated as determined by enzyme-linked
immunosorbent assay and a glycan microarray screening study. The production
of high titers of IgG antibodies suggested that the TMV platform contained
the requisite epitopes for helper T cells and was able to induce antibody
isotype switching. The antibodies exhibited strong reactivities toward
Tn antigen displayed in its native environment, i.e., cancer cell
surface, thus highlighting the potential of TMV as a promising TACA
carrier
Boosting Immunity to Small Tumor-Associated Carbohydrates with Bacteriophage Qβ Capsids
The development of an effective immunotherapy
is an attractive
strategy toward cancer treatment. Tumor associated carbohydrate antigens
(TACAs) are overexpressed on a variety of cancer cell surfaces, which
present tempting targets for anticancer vaccine development. However,
such carbohydrates are often poorly immunogenic. To overcome this
challenge, we show here that the display of a very weak TACA, the
monomeric Tn antigen, on bacteriophage Qβ virus-like particles
elicits powerful humoral responses to the carbohydrate. The effects
of adjuvants, antigen display pattern, and vaccine dose on the strength
and subclasses of antibody responses were established. The local density
of antigen rather than the total amount of antigen administered was
found to be crucial for induction of high Tn-specific IgG titers.
The ability to display antigens in an organized and high density manner
is a key advantage of virus-like particles such as Qβ as vaccine
carriers. Glycan microarray analysis showed that the antibodies generated
were highly selective toward Tn antigens. Furthermore, Qβ elicited
much higher levels of IgG antibodies than other types of virus-like
particles, and the IgG antibodies produced reacted strongly with the
native Tn antigens on human leukemia cells. Thus, Qβ presents
a highly attractive platform for the development of carbohydrate-based
anticancer vaccines
Sugar-Binding Proteins from Fish: Selection of High Affinity “Lambodies” That Recognize Biomedically Relevant Glycans
Glycan-binding proteins are important for a wide variety
of basic
research and clinical applications, but proteins with high affinity
and selectivity for carbohydrates are difficult to obtain. Here we
describe a facile and cost-effective strategy to generate monoclonal
lamprey antibodies, called lambodies, that target glycan determinants.
We screened a library of yeast surface-displayed (YSD) lamprey variable
lymphocyte receptors (VLR) for clones that can selectively bind various
biomedically important glycotopes. These glycoconjugates included
tumor-associated carbohydrate antigens (Tn and TFα), Lewis antigens
(LeA and LeX), <i>N</i>-glycolylneuraminic acid, targets
of broadly neutralizing HIV antibodies (poly-Man9 and the HIV gp120),
and the glycoproteins asialo-ovine submaxillary mucin (aOSM) and asialo-human
glycophorin A (aGPA). We isolated clones that bind each of these targets
in a glycan-dependent manner and with very strong binding constants,
for example, 6.2 nM for Man9 and 44.7 nM for gp120, determined by
surface plasmon resonance (SPR). One particular lambody, VLRB.aGPA.23,
was shown by glycan array analysis to be selective for the blood group
H type 3 trisaccharide (BG-H3, Fucα1-2Galβ1-3GalNAcα),
aGPA, and TFα (Galβ1-3GalNAcα), with affinity constants
of 0.2, 1, and 8 nM, respectively. In human tissue microarrays this
lambody selectively detected cancer-associated carbohydrate antigens
in 14 different types of cancers. It stained 27% of non-small cell
lung cancer (NSCLC) samples in a pattern that correlated with poor
patient survival. Lambodies with exquisite affinity and selectivity
for glycans may find myriad uses in glycobiology and biomedical research
Sugar-Binding Proteins from Fish: Selection of High Affinity “Lambodies” That Recognize Biomedically Relevant Glycans
Glycan-binding proteins are important for a wide variety
of basic
research and clinical applications, but proteins with high affinity
and selectivity for carbohydrates are difficult to obtain. Here we
describe a facile and cost-effective strategy to generate monoclonal
lamprey antibodies, called lambodies, that target glycan determinants.
We screened a library of yeast surface-displayed (YSD) lamprey variable
lymphocyte receptors (VLR) for clones that can selectively bind various
biomedically important glycotopes. These glycoconjugates included
tumor-associated carbohydrate antigens (Tn and TFα), Lewis antigens
(LeA and LeX), <i>N</i>-glycolylneuraminic acid, targets
of broadly neutralizing HIV antibodies (poly-Man9 and the HIV gp120),
and the glycoproteins asialo-ovine submaxillary mucin (aOSM) and asialo-human
glycophorin A (aGPA). We isolated clones that bind each of these targets
in a glycan-dependent manner and with very strong binding constants,
for example, 6.2 nM for Man9 and 44.7 nM for gp120, determined by
surface plasmon resonance (SPR). One particular lambody, VLRB.aGPA.23,
was shown by glycan array analysis to be selective for the blood group
H type 3 trisaccharide (BG-H3, Fucα1-2Galβ1-3GalNAcα),
aGPA, and TFα (Galβ1-3GalNAcα), with affinity constants
of 0.2, 1, and 8 nM, respectively. In human tissue microarrays this
lambody selectively detected cancer-associated carbohydrate antigens
in 14 different types of cancers. It stained 27% of non-small cell
lung cancer (NSCLC) samples in a pattern that correlated with poor
patient survival. Lambodies with exquisite affinity and selectivity
for glycans may find myriad uses in glycobiology and biomedical research
Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine
Development of an effective vaccine
targeting tumor associated
carbohydrate antigens (TACAs) is an appealing approach toward tumor
immunotherapy. While much emphasis has been typically placed on generating
high antibody titers against the immunizing antigen, the impact of
immunogen design on the diversity of TACA-specific antibodies elicited
has been overlooked. Herein, we report that the immunogen structure
can significantly impact the breadth and the magnitude of humoral
responses. Vaccine constructs that induced diverse TACA-binding antibodies
provided much stronger recognition of a variety of Tn positive tumor
cells. Optimization of the breadth of the antibody response led to
a vaccine construct that demonstrated long lasting efficacy in a mouse
tumor model. After challenged with the highly aggressive TA3Ha cells,
mice immunized with the new construct exhibited a statistically significant
improvement in survival relative to controls (0% vs 50% survival; <i>p</i> < 0.0001). Furthermore, the surviving mice developed
long-term immunity against TA3Ha. Thus, both the magnitude and the
breadth of antibody reactivity should be considered when designing
TACA-based antitumor vaccines