Study of immunogenicity and safety of a candidate rotavirus vaccine based on a recombinant hybrid protein

2021 ◽  
Vol 21 (2) ◽  
pp. 87-98
Author(s):  
Elena A. Varyushina ◽  
Georgy V. Alexandrov ◽  
Mikhail S. Zakharov ◽  
Anna S. Kiryanova ◽  
Olga E. Huttunen ◽  
...  

BACKGROUND: Rotaviruses are the main cause of acute gastroenteritis in children in both developed and developing countries. Vaccination is the only way to prevent severe and fatal course of this disease. Live attenuated viruses-based vaccines currently available can have a number of side effects. A candidate rotavirus vaccine reported is based on a hybrid recombinant protein FliCVP6VP8, which includes a VP6 protein fragment, a rotavirus A VP8 protein fragment, and S. typhimurium FliC flagellin components. AIM: The aim was to evaluate the immunogenicity and safety of а preparation Rotavirus vaccine, recombinant in preclinical studies. MATERIALS AND METHODS: The immunogenicity of vaccine (blood antibody titers, antigen-specific proliferative response of spleen cells) was evaluated in BALB/c mice. The acute and subchronic toxicity, the possible irritating effect, pyrogenicity and the anaphylactic effect and delayed type hypersensitivity were evaluated in laboratory mice, rats, Guinea pigs, and rabbits. RESULTS: Double immunization of mice with the candidate vaccine demonstrated a significant increase in antibody titers in mouse sera compared to that in control mice. Evaluation of antigen-specific proliferative response after double immunization with a candidate vaccine demonstrated a significant increase in the values of stimulated proliferation. Evaluation of safety through acute and chronic toxicity studies demonstrated no toxicity. The immunostimulatory effect of vaccine was demonstrated when evaluating the number of antibody-producing cells with sheep red blood cells as antigens. The number of white blood cells was demonstrated to increase after the prolonged vaccine administration. CONCLUSIONS: The preclinical studies have demonstrated safety of the candidate rotavirus vaccine and its capability to produce the immune response.

1963 ◽  
Vol 118 (6) ◽  
pp. 1021-1035 ◽  
Author(s):  
Jack R. Battisto ◽  
Merrill W. Chase

Guinea pigs fed picryl chloride to induce specific immunologic unresponsiveness cleared small amounts of venously infused antipicryl antibody at a rate equal to that of normal guinea pigs. Catabolism of passively administered picryl-specific antibody did not alter the unresponsive state of picryl chloride-fed guinea pigs or the responsive state of normal guinea pigs. Lymphoid cells of picryl chloride immunized guinea pigs produced equal amounts of picryl-specific antibody in picryl chloride-fed and normal animals. Allergen-fed guinea pigs remained unresponsive to attempted sensitization with the allergen in excess of 10 months after the final feeding, though some became feebly sensitive between 9 and 11 months. Second attempts to make unresponsive animals hypersensitive were unsuccessful. White blood cells of guinea pigs unresponsive to picryl chloride were unable to transfer delayed-type hypersensitivity for picryl chloride to normal recipients yet readily transferred tuberculin hypersensitivity.


1974 ◽  
Vol 139 (3) ◽  
pp. 543-559 ◽  
Author(s):  
G. B. Mackaness ◽  
P. H. Lagrange ◽  
T. E. Miller ◽  
T. Ishibashi

An explanation was sought for the fact that delayed-type hypersensitivity (DTH) does not normally occur in response to T-cell-dependent antigens unless an adjuvant is used. But when sheep red blood cells (SRBC) were administered intravenously DTH did appear, provided that the dose of antigen was less than that required to give a maximum antibody response. Animals in which T-cell activity had been blocked by a large dose of antigen could not be sensitized adoptively, and their spleen cells failed to transfer DTH to normal recipients. The serum of blocked animals partially inhibited the induction of DTH, and after absorption with SRBC its blocking activity increased substantially. Moreover, absorbed serum inhibited DTH in previously sensitized animals, but it did not inhibit the proliferative response to SRBC in peripheral lymph nodes or reduce the number of plaque-forming cells produced therein. On the contrary, the hemagglutinating titer was actually increased by blocking serum even though DTH was totally suppressed. It is concluded that a product of the interaction between antigens and antibody blocks the activated T cells which mediate DTH without interfering with helper cells.


Author(s):  
Delma P. Thomas ◽  
Dianne E. Godar

Ultraviolet radiation (UVR) from all three waveband regions of the UV spectrum, UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm), can be emitted by some medical devices and consumer products. Sunlamps can expose the blood to a considerable amount of UVR, particularly UVA and/or UVB. The percent transmission of each waveband through the epidermis to the dermis, which contains blood, increases in the order of increasing wavelength: UVC (10%) < UVB (20%) < UVA (30%). To investigate the effects of UVR on white blood cells, we chose transmission electron microscopy to examine the ultrastructure changes in L5178Y-R murine lymphoma cells.


1990 ◽  
Vol 63 (01) ◽  
pp. 112-121 ◽  
Author(s):  
David N Bell ◽  
Samira Spain ◽  
Harry L Goldsmith

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.


2013 ◽  
Author(s):  
Olga Papalou ◽  
Sarantis Livadas ◽  
Athanasios Karachalios ◽  
Nektarios Benetatos ◽  
George Boutzios ◽  
...  

2014 ◽  
Vol 23 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Christos Triantos ◽  
Emmanuel Louvros ◽  
Maria Kalafateli ◽  
Anne Riddell ◽  
Ulrich Thalheimer ◽  
...  

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 noncirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleedingbut was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)].Conclusions: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti-Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.List of abbreviations: AFP, alpha-fetoprotein; aPTT, activated partial thromboplastin time; CP, Child-Pugh; FXa, activated factor X; GAGS, glycosaminoglycans; Hb, hemoglobin; HCC, hepatocellular carcinoma; HVPG, hepatic venous pressure gradient; INR, International normalized ratio; LMWHs, low molecular weight heparins; MELD, Model for End-stage Liver Disease; PPP, platelet-poor plasma; PRBC, packed red blood cells; PT, prothrombin time; SBP, sponataneous bacterial peritonitis; TEG, thromboelastography; WBC, white blood cells.


2012 ◽  
Author(s):  
Erin Sandford ◽  
Megan Orr ◽  
Xianyao Li ◽  
Huaijun Zhou ◽  
timothy J. Johnson ◽  
...  

Author(s):  
Ranu Kumar ◽  
Prasad Kapildeo

We are traditionally used Microscope in clinical laboratory for determination of white blood cells of human blood smear. Now, in this study we were used Foldscope with Smartphone in the place of Microscope and examine many samples of human blood smear which was collected from local diagnostic centers. We were very easily quantity & morphology analysis of all types of WBC cells such as Neutrophils, Lymphocytes, Monocytes, Eosionophils, Basophils in blood smear with the help of Foldscope & image taken by Smartphone. The main objective of this study is to use Foldscope for quantity & morphology analysis of human WBCs at field level especially poor resource area where healthcare services or centers is not available & where carry of microscope is not possible.


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