Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized,Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata,India

Background

A live oral cholera vaccine VA 1.4 developed from a non-toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1∶1 for safety and immunogenicity in men and women aged 18–60 years from Kolkata, India.

Method

A lyophilized dose of 1.9×10⁹ CFU (n = 44) or a placebo (n = 43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14.

Result

The vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%–79.5%) at both 7 days (i.e. after 1^st dose) and 21 days (i.e. after 2^nd dose). None of the placebo recipients seroconverted. Anti-cholera toxin antibody was detected in very few recipients of the vaccine.

Conclusion

This study demonstrates that VA 1.4 at a single dose of 1.9×10⁹ is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen.

Trial Registration

Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582     

Coryphoid Palm Leaf Fossils from the Maastrichtian–Danian of Central India with Remarks on Phytogeography of the Coryphoideae (Arecaceae)

Premise of research

A large number of fossil coryphoid palm wood and fruits have been reported from the Deccan Intertrappean beds of India. We document the oldest well-preserved and very rare costapalmate palm leaves and inflorescence like structures from the same horizon.

Methodology

A number of specimens were collected from Maastrichtian–Danian sediments of the Deccan Intertrappean beds, Ghughua, near Umaria, Dindori District, Madhya Pradesh, India. The specimens are compared with modern and fossil taxa of the family Arecaceae.

Pivotal results

Sabalites dindoriensis sp. nov. is described based on fossil leaf specimens including basal to apical parts. These are the oldest coryphoid fossil palm leaves from India as well as, at the time of deposition, from the Gondwana- derived continents.

Conclusions

The fossil record of coryphoid palm leaves presented here and reported from the Eurasian localities suggests that this is the oldest record of coryphoid palm leaves from India and also from the Gondwana- derived continents suggesting that the coryphoid palms were well established and wide spread on both northern and southern hemispheres by the Maastrichtian–Danian. The coryphoid palms probably dispersed into India from Europe via Africa during the latest Cretaceous long before the Indian Plate collided with the Eurasian Plate.     

Consequences of Whole-Genome Triplication as Revealed by Comparative Genomic Analyses of the Wild Radish Raphanus raphanistrum and Three Other Brassicaceae Species

Polyploidization events are frequent among flowering plants, and the duplicate genes produced via such events contribute significantly to plant evolution. We sequenced the genome of wild radish (Raphanus raphanistrum), a Brassicaceae species that experienced a whole-genome triplication event prior to diverging from Brassica rapa. Despite substantial gene gains in these two species compared with Arabidopsis thaliana and Arabidopsis lyrata, ∼70% of the orthologous groups experienced gene losses in R. raphanistrum and B. rapa, with most of the losses occurring prior to their divergence. The retained duplicates show substantial divergence in sequence and expression. Based on comparison of A. thaliana and R. raphanistrum ortholog floral expression levels, retained radish duplicates diverged primarily via maintenance of ancestral expression level in one copy and reduction of expression level in others. In addition, retained duplicates differed significantly from genes that reverted to singleton state in function, sequence composition, expression patterns, network connectivity, and rates of evolution. Using these properties, we established a statistical learning model for predicting whether a duplicate would be retained postpolyploidization. Overall, our study provides new insights into the processes of plant duplicate loss, retention, and functional divergence and highlights the need for further understanding factors controlling duplicate gene fate.     

Description of Goffartia phalacra n. sp. (Diplogastridae: Nematoda) from India

A new species, Goffartia phalacra n. sp. is described and illustrated. The body is thin and slender with L = 511 to 646 μm; a = 37.1 to 47.4; b = 4.8 to 6; c = 2.6 to 4.8; c′ = 13.6 to 32.8; V = 40% to 49% in females. Males are smaller but similar to females and the posterior region is strongly curved. The species is characterized by a tubular stoma, a smooth round lip region, anterior pharynx much smaller than posterior pharynx, two pairs of unicellular glands associated with the vagina, and males with a broad keel-shaped gubernaculum. G. phalacra n. sp. can be differentiated from all other species of the genus by its lip region and the structure of the gubernaculum. This is the first instance of a species of Goffartia occurring in a terrestrial habitat and the first report of a species from India.     

TbTRF suppresses the TERRA level and regulates the cell cycle-dependent TERRA foci number with a TERRA binding activity in its C-terminal Myb domain

Telomere repeat-containing RNA (TERRA) has been identified in multiple organisms including Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. T. brucei regularly switches its major surface antigen, VSG, to evade the host immune response. VSG is expressed exclusively from subtelomeric expression sites, and we have shown that telomere proteins play important roles in the regulation of VSG silencing and switching. In this study, we identify several unique features of TERRA and telomere biology in T. brucei. First, the number of TERRA foci is cell cycle-regulated and influenced by TbTRF, the duplex telomere DNA binding factor in T. brucei. Second, TERRA is transcribed by RNA polymerase I mainly from a single telomere downstream of the active VSG. Third, TbTRF binds TERRA through its C-terminal Myb domain, which also has the duplex DNA binding activity, in a sequence-specific manner and suppresses the TERRA level without affecting its half-life. Finally, levels of the telomeric R-loop and telomere DNA damage were increased upon TbTRF depletion. Overexpression of an ectopic allele of RNase H1 that resolves the R-loop structure in TbTRF RNAi cells can partially suppress these phenotypes, revealing an underlying mechanism of how TbTRF helps maintain telomere integrity.     

Development and Gamma Scintigraphy Study of <Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> (Fenugreek) Polysaccharide-Based Colon Tablet

The major concern with the use of some synthetic excipients is their safety towards biological tissues, hence influencing the reliability of products. With the aim to minimize dependency on highly toxic synthetic excipients, the present study was designed to deliver metronidazole (MNZ) into the colonic region for localized treatment of amoebiasis using natural polysaccharide-based drug delivery. Compression-coated tablets were prepared using water extractable natural polysaccharide from Trigonella foenum-graecum (FG). Physical properties of the tablets were evaluated and dissolution study was performed at pH 1.2, 6.8, and 7.4 with rat cecal material. Results indicate that all batches demonstrated pH-dependent drug release and prevented release into the stomach, allowing traces into the intestine and highest availability into the colon. A significant correlation (r²?=?0.975) was found between the coating levels of extracted polysaccharide and lag time release of drug. Gamma scintigraphy images of in vivo study conducted on human volunteers showed a small intestinal transit time, i.e., 3–5 (4.2?±?0.4) h and confirmed that the tablets reached the colon within 6–8 h. The present study revealed that the FG polysaccharide-based double compression tablets may be promising colon-specific drug carriers with reduced toxic effects of commonly used synthetic excipients.