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     

Biomass and Total Lipid Content Assessment of Microalgal Cultures Using Near and Short Wave Infrared Spectroscopy

The technique of near and short wave near-infrared spectroscopy was assessed with respect to analysis of dry matter and lipid content of microalgae with potential for biodiesel production. Microalgal culture samples were filtered through GF/C filter papers and spectral measurements of wet and oven dried (60 °C overnight) filter papers over the ranges of 300–1,100 nm and 1,100–2,500 nm were recorded. Partial least square models on culture biomass and lipid content for combined species data were poor in terms of RMSECV, R _CV and the ratio of RMSECV to SD. A single species model for C. vulgaris based on 1,100–2,500 nm spectra of dry filtrate supported a model with RMSECV, R _CV and SDR values of 0.32 g L^?1, 0.955 and 3.38 for biomass and 0.089 g L^?1, 0.874 and 2.06 with lipid, respectively. However, the dry filtrate models on biomass and lipid content performed poorly in the prediction of samples drawn from an independent series of C. vulgaris cultured under N-, P- and Fe-limited growth trial. Thus, while the near-infrared spectroscopy technique has potential for assessment of dry matter and lipid content of microalgal cultures using a dried filtrate sample, further work is required to examine the limits to model robustness.     

Hydro and halo priming: influenced germination responses in wheat Var-HUW-468 under heavy metal stress

The beneficial effect of seed priming in improving critical growth stages like seed germination and early growth phases has been accepted by Plant Physiologists for many important field crops. In the present investigation, studies were made to see the effect of heavy metal stress imposed during germination using solution of HgCl₂ in four different concentrations (0.0, 0.50, 0.75 and 1.00 mM) in Petri dishes on primed and non-primed seeds of wheat. Priming has been done with distilled water (hydro), Mg(NO₃)₂ and Ca(NO₃)₂ (halo) salts. Different germination parameters, such as germination percentage, radicle and plumule lengths, seedling emergence, soluble and insoluble sugar contents and activity of α-amylase in endosperm were studied at different study periods. Primed seeds increased all the germination parameters except insoluble sugar content in respect to non-primed control in the absence of HgCl₂. However, the use of primed seeds has shown to overcome the inhibitory effects of heavy metal stress imposed in the form of HgCl₂ solution during the period of germination. Hence, the work concludes the mitigating effects of priming under heavy metal stress.     

Ingestion without inactivation of bacteriophages by Tetrahymena

Tetrahymena has been shown to ingest and inactivate bacteriophages, such as T4, in co-incubation experiments. In this study, Tetrahymena thermophila failed to inactivate phages PhiX174 and MS2 in co-incubations, although PhiX174 were ingested by T. thermophila, as demonstrated by: (1) recovery at defecation in a pulse-chase experiment, (2) recovery from Tetrahymena by detergent lysis, and (3) transmission electron microscopy. We conclude, therefore, that the phages must be digestion-resistant. Internalized PhiX174 were further shown to be partially protected from lethal damage by ultraviolet (UV) C and UVB irradiation. Finally, ingested PhiX174 were shown to be rapidly transported through buffer in a horizontal swimming, race tube-like assay. The transport and protection of phages may confer evolutionary advantages that explain the acquisition of digestion-resistance by some phages.     

Seasonality,crop type and crop phenology influence crop damage by wildlife herbivores in Africa and Asia

Wildlife species damaging crops can cause substantial losses to farmers and at the same time create negative attitudes against wildlife and conservation efforts that may result in negative interactions against wildlife and lead to human-wildlife conflicts (HWCs). For the analysis of negative interactions between humans and terrestrial wildlife species, a globally applicable scheme for monitoring was developed and applied over 6 years in study areas of two Asian (Nepal and India) and two African (Zambia and Tanzania) countries. Factors influencing crop consumption by eight different groups of herbivores were monitored and analyzed using generalized linear models. Seasonality, crop availability, type and the phenological stage of the crop seem to play an important role in the crop damaging behavior of herbivores. Crop consumers such as elephants (Loxodonta africana and Elephas maximus), zebra (Equus quagga spp.) and boars/hogs (Sus scrofa, Potamocherus larvatus and Phacochoerus africanus) show preferences for harvested and/or maturing crops. Rhinos (Rhinoceros unicornis) and antelopes/deer (Taurotragus oryx, Aepyceros melampus, Boselaphus tragocamelus and Axis axis) damage the highest numbers of fields with crops at an intermediate growth stage. The findings of this study can inform management of HWCs in areas where people and wildlife coexist. Furthermore, this study demonstrates the benefits of standardized HWC assessments in order to compare data from different continents and between different species to be able to draw generalized conclusions for the management of HWC.     

Microalgal fatty acid composition: rapid assessment using near-infrared spectroscopy

The feasibility of assessing microalgal fatty acid composition using near-infrared spectroscopy (NIRS) is described. The chlamydomonad microalga, Rhopalosolen saccatus (previously known as Characium saccatum), was isolated from the Fitzroy River, Central Queensland, Australia. R. saccatus was grown in batch culture with varying phosphorus nutrition and assessed for dry matter, total lipid and fatty acid composition using gas chromatography (GC). Transmission spectra (1100–2500 nm) were acquired of liquid culture, and reflectance spectra were acquired of wet and dry filtrates of cultures and of methyl esters. Partial least square (PLS) regression models were built on biomass, total lipid and a number of fatty acids. All sample presentation models supported PLS regression model with a cross validation correlation coefficient (R _cv) >0.87 for biomass and R _cv >0.68 for total lipid; however, the use of dry filtrates of culture is recommended as the sample presentation mode of choice. Models for fatty acids based on culture transmission spectra, reflectance spectra of wet and dry culture filtrates, or reflectance spectra of methyl esters in solvent were not acceptable. Dry extracts of methyl esters supported adequate models for fatty acids from C8:0 to C22:0, with the exception of capric and behenic acids, with an R _cv of 0.89–0.94; however, in practice, samples processed to this stage can be easily analyzed by GC. Near-infrared spectroscopy can be a potential choice for rapid estimation of biomass (dry matter) and lipid content and composition in microalgae, with further work required to demonstrate oping robustness of the calibration model in prediction of unknown samples.     

The immunoglobulin G1 N-glycan composition affects binding to each low affinity Fc γ receptor

Immunoglobulin G1 (IgG1) is the most abundant circulating human antibody and also the scaffold for many therapeutic monoclonal antibodies (mAbs). The destruction of IgG-coated targets by cell-mediated pathways begins with an interaction between the IgG Fc region and multiple varieties of membrane-bound Fc γ receptors (FcγRs) on the surface of leukocytes. This interaction requires the presence of an asparagine-linked (N-)glycan on the Fc, and variations in the N-glycan composition can affect the affinity of CD16A binding (an FcγR). Contemporary efforts to glycoengineer mAbs focus on increasing CD16A affinity, and thus treatment efficacy, but it is unclear how these changes affect affinity for the other FcγRs. Here, we measure binding of the extracellular Fc-binding domains for human CD16A and B, CD32A, B and C, and CD64 to 6 well-defined IgG1 Fc glycoforms that cover ～85% of the pool of human IgG1 Fc glycoforms. Core α1–6 fucosylation showed the greatest changes with CD16B (8.5-fold decrease), CD16A (3.9-fold decrease) and CD32B/C (1.8-fold decrease), but did not affect binding to CD32A. Adding galactose to the non-reducing termini of the complex-type, biantennary glycan increased affinity for all CD16s and 32s tested by 1.7-fold. Sialylation did not change the affinity of core-fucosylated Fc, but increased the affinity of afucosylated Fc slightly by an average of 1.16-fold for all CD16s and CD32s tested. The effects of fucose and galactose modification are additive, suggesting the contributions of these residues to Fc γ receptor affinity are independent.     

Concept, measurement and use of acculturation in health and disease risk studies

Acculturation, a concept with its root in social science and cultural anthropology, is a process intimately related to health behavior and health status of minority populations in a multicultural society. This paper provides a brief review of the subject of acculturation as it relates to health research, showing that this concept has a potential to identify risk factors that underlie increased prevalence of chronic diseases, particularly in immigrant populations. A proper understanding of this is helpful in designing intervention programs to reduce the burden of such diseases and to increase the quality of life in such populations. The concept is defined with an outline of its history showing its evolution over time. Criteria for measuring acculturation are described to illustrate the need of accommodating its multidimensional features. Drawing examples from health research in US Hispanics, the role of acculturation on health behavior is discussed to document that the discordant findings are at least partially due to either use of incomplete dimensions of the concept, or not accounting for the dynamic aspect of its process. Finally, with illustration of a finding from a study among overweight Mexican American women of South Texas, a model of acculturation study is proposed that may be used in other immigrant populations undergoing the acculturation process.