Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

The emergence of SARS-CoV-2 variants may impact the effectiveness of vaccines, while heterologous vaccine strategy is considered to provide better protection. The immunogenicity of an mRNA-inactivated virus vaccine against the SARS-CoV-2 wild-type (WT) and variants was evaluated in the study. SARS-CoV-2 naïve adults (n = 123) were recruited and placed in the following groups: BNT162b2, CoronaVac or BNT162b2-CoronaVac (Combo) Group. Blood samples were collected to measure neutralization antibodies (NAb) by a live virus microneutralization assay (vMN) and surrogate NAb test. The day 56 vMN geometric mean titre (GMT) was 26.2 [95% confident interval (CI), [22.3–30.9] for Combo, 136.9 (95% CI, 104.2–179.7) for BNT162b2, and 14.7 (95% CI, 11.6–18.6) for CoronaVac groups. At 6 months post-first dose, the GMT declined to 8.0, 28.8 and 7.1 in the Combo, BNT162b2 and CoronaVac groups, respectively. Three groups showed reduced neutralizing activity against D614G, beta, theta and delta variants. At day 56 GMT (74.6) and month 6 GMT (22.7), the delta variant in the BNT162b2 group was higher than that in the Combo (day 56, 7.4; month 6, 5.5) and CoronaVac groups (day 56, 8.0; month 6, 5) (p < 0.0001). Furthermore, the mean surrogate NAb value on day 56 in the BNT162b2 group was 594.7 AU/mL and higher than 40.5 AU/mL in Combo and 38.8 AU/mL in CoronaVac groups (p < 0.0001). None of the participants developed severe adverse events, and all other adverse events were self-limiting. The Combo vaccination strategy was safe. The overall vaccine immunogenicity at day 56 and 6 months were comparable to the homologous CoronaVac group but inferior to the homologous BNT162b2 group, against both the WT and all variants. Furthermore, the antibody response of vaccines waned at 6 months and thereby, a third dose of the vaccine is needed for these vaccines.

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Antibody Response of BNT162b2 and CoronaVac Platforms in Recovered Individuals Previously Infected by COVID-19 against SARS-CoV-2 Wild Type and Delta Variant

Vaccines ◽

10.3390/vaccines9121442 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1442

Author(s):

Ruiqi Zhang ◽

Ka-Wa Khong ◽

Ka-Yi Leung ◽

Danlei Liu ◽

Yujing Fan ◽

...

Keyword(s):

Antibody Response ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Fold Increase ◽

Neutralization Assay ◽

Wild Type ◽

Vaccine Platform ◽

Live Virus ◽

Virus Neutralization Assay ◽

Geometric Mean Titre

Vaccinating recovered patients previously infected by COVID-19 with mRNA vaccines to boost their immune response against wild-type viruses (WT), we aimed to investigate whether vaccine platform and time of vaccination affect immunogenicity against the SARS-CoV-2 WT and Delta variant (DV). Convalescent patients infected by COVID-19 were recruited and received one booster dose of the BNT162b2 (PC-B) or CoronaVac (PC-C) vaccines, while SARS-CoV-2 naïve subjects received two doses of the BNT162b2 (CN-B) or CoronaVac (CN-C) vaccines. The neutralizing antibody in sera against the WT and DV was determined with live virus neutralization assay (vMN). The vMN geometric mean titre (GMT) against WT in recovered individuals previously infected by COVID-19 reduced significantly from 60.0 (95% confidence interval (CI), 46.5–77.4) to 33.9 (95% CI, 26.3–43.7) at 6 months post recovery. In the PC-B group, the BNT162b2 vaccine enhanced antibody response against WT and DV, with 22.3-fold and 20.4-fold increases, respectively. The PC-C group also showed 1.8-fold and 2.2-fold increases for WT and DV, respectively, after receiving the CoronaVac vaccine. There was a 10.6-fold increase in GMT in the CN-B group and a 1.3-fold increase in the CN-C group against DV after full vaccination. In both the PC-B and PC-C groups, there was no difference between GMT against WT and DV after vaccination. Subjects in the CN-B and CN-C groups showed inferior GMT against DV compared with GMT against WT after vaccination. In this study, one booster shot effectively enhanced the pre-existing neutralizing activity against WT and DV in recovered subjects.

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A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa414 ◽

2020 ◽

Author(s):

Marie-Astrid Hoogerwerf ◽

Jan Pieter R Koopman ◽

Jacqueline J Janse ◽

Marijke C C Langenberg ◽

Roos van Schuijlenburg ◽

...

Keyword(s):

Adverse Events ◽

Controlled Trial ◽

Geometric Mean ◽

Egg Load ◽

Infectious Dose ◽

Randomized Controlled ◽

Vaccine Trials ◽

The Mean ◽

Bayesian Statistical Modeling ◽

Hookworm Infections

Abstract Background Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability, and egg output of repeated exposure to hookworm larvae. Methods Twenty-four healthy volunteers were randomized, double-blindly, to 1, 2, or 3 doses of 50 Necator americanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20. Results There was no association between larval dose and number or severity of adverse events. Geometric mean egg loads stabilized at 697, 1668, and 1914 eggs per gram feces for the 1 × 50L3, 2 × 50L3, and 3 × 50L3 group, respectively. Bayesian statistical modeling showed that egg count variability relative to the mean was reduced with a second infectious dose; however, the third dose did not increase egg load or decrease variability. We therefore suggest 2 × 50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes the power of hypothetical vaccine trials. Conclusions Repeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events. Clinical Trials Registration NCT03257072.

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Effect of the African Traditional Medicine,Sutherlandia frutescens, on the Bioavailability of the Antiretroviral Protease Inhibitor, Atazanavir

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/324618 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Adrienne C. Müller ◽

Michael F. Skinner ◽

Isadore Kanfer

Keyword(s):

Single Dose ◽

Geometric Mean ◽

Plasma Concentrations ◽

Time Profile ◽

Blood Samples ◽

Concentration Time ◽

The Mean ◽

Male Subjects ◽

Anti Hiv ◽

Sutherlandia Frutescens

The objective of this study was to investigate the effect ofSutherlandia frutescens(SF) on the bioavailability of atazanavir (ATV) in twelve healthy male subjects. During Phase I (Day 1), subjects ingested a single dose of ATV and blood samples were drawn before dose and at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12, 18, and 24 hours after dose. From Day 3 to Day 14, a single dose of milled SF was administered twice daily to each subject. During Phase II, Day 15, subjects ingested single doses of ATV and SF. Blood samples were drawn as previously described. Plasma was harvested from blood samples and the concentration of ATV therein was determined. For each phase, the mean ATV plasma concentration-time profile was plotted and the means ofAUC0–24andCmaxfor ATV were computed. The geometric mean ratios and confidence intervals (CIs) forCmaxandAUC0–24 hrwere 0.783 (0.609–1.00) and 0.801 (0.634–1.01), respectively. The CIs for both PK parameters fell below the limits of the “no-effect” boundary, set at 0.8–1.25, indicating that SF significantly reduced the bioavailability of ATV. This may potentially result in subtherapeutic plasma concentrations and thus reduced anti-HIV efficacy of ATV.

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Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine

10.1101/2021.11.05.21264700 ◽

2021 ◽

Author(s):

Surakameth Mahasirimongkol ◽

Athiwat Khunphon ◽

Oraya Kwangsukstid ◽

Sompong Sapsutthipas ◽

Minkwan Wichaidit ◽

...

Keyword(s):

Adverse Events ◽

Virus Vaccine ◽

Viral Vector ◽

Natural Infection ◽

Geometric Mean ◽

Wild Type ◽

Vaccine Regimen ◽

Vector Vaccine ◽

Boost Vaccine ◽

Viral Vector Vaccine

Background: Responding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. Method: Immunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. Result: Between April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks ( 873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152 ,and I/I group 108.2 ,95% CI 77-152 ; all p<0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p<0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. Conclusion: The I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.

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Three Doses of an Experimental Detoxified L3-Derived Lipooligosaccharide Meningococcal Vaccine Offer Good Safety but Low Immunogenicity in Healthy Young Adults

Clinical and Vaccine Immunology ◽

10.1128/cvi.00129-10 ◽

2010 ◽

Vol 17 (9) ◽

pp. 1460-1466 ◽

Cited By ~ 13

Author(s):

Pablo Bonvehí ◽

Dominique Boutriau ◽

Javier Casellas ◽

Vincent Weynants ◽

Christiane Feron ◽

...

Keyword(s):

Young Adults ◽

Adverse Events ◽

Membrane Vesicle ◽

Geometric Mean ◽

Fold Increase ◽

Wild Type ◽

Serious Adverse Events ◽

Level 3 ◽

To Receive ◽

Type Strains

ABSTRACT This open, randomized phase I study evaluated the safety and reactogenicity of an experimental meningococcal serogroup B (MenB) vaccine obtained from outer membrane vesicle detoxified L3-derived lipooligosaccharide. Healthy young adults (n = 150) were randomized to receive either experimental vaccine (provided in five formulations, n = 25 in each group) or VA-Mengoc-BC (control, n = 25) administered on a 0- to 6-week/6-month schedule. Serum bactericidal assays performed against three MenB wild-type strains assessed the immune response, defined as a 4-fold increase from pre- to postvaccination. No serious adverse events related to vaccination were reported. Pain at the injection site, fatigue, and headache were the most commonly reported adverse events. Solicited adverse events graded level 3 (i.e., preventing daily activity) were pain (up to 17% of the test subjects versus 32% of the controls), fatigue (up to 12% of the test subjects versus 8% of the controls), and headache (up to 4% of any group). Swelling graded level 3 (greater than 50 mm) occurred in up to 4% of the test subjects versus 8% of the controls. The immune responses ranged from 5% to 36% across experimental vaccines for the L3 H44-76 strain (versus 27% for the control), from 0% to 11% for the L3 NZ98/124 strain (versus 23% for the control), and from 0% to 13% for the L2 760676 strain (versus 59% for the control). All geometric mean titers were below those measured with the control vaccine. The five experimental formulations were safe and well tolerated but tended to be less immunogenic than the control vaccine.

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Correlation between Commercial Anti-RBD IgG Titer and Neutralization Titer against SARS-CoV-2 Beta Variant

Diagnostics ◽

10.3390/diagnostics11122216 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2216

Author(s):

Rosana Wing-Shan Poon ◽

Lu Lu ◽

Carol Ho-Yan Fong ◽

Tak-Chuen Ip ◽

Lin-Lei Chen ◽

...

Keyword(s):

Antibody Titer ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Antibody Concentration ◽

Wild Type ◽

Neutralization Titer ◽

Receptor Binding Site ◽

Live Virus ◽

Antibody Assays

Objectives: The emergence of SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of vaccines and are associated with a rebound in the number of COVID-19 cases globally. These variants contain mutations at the spike (S) protein receptor binding site (RBD), which affect antibody binding. Current commercially available antibody assays were developed before the VOCs emerged. It is unclear whether the levels of these commercially available antibody assays can predict the neutralizing antibody titers against the VOCs. In this study, we sought to determine the correlation between the binding antibody concentration and microneutralization antibody titer against the beta variant. Methods: This study included 58 COVID-19 patients. The concentrations of IgG against the SARS-CoV-2 spike protein RBD and nucleocapsid (N) protein were measured using the Abbott SARS-CoV-2 IgG II Quant assay and the SARS-CoV-2 IgG assay, respectively. The neutralization antibody titer against the wild type lineage A SARS-CoV-2 and against the beta variant (B.1.351) was determined using a conventional live virus neutralization test. Results: The geometric mean MN titer (GMT) against the beta variant was significantly lower than that against the wild type lineage A virus (5.6 vs. 47.3, P<0.0001). The anti-RBD IgG had a better correlation with the neutralizing antibody titer than that of the anti-N IgG assay against the wild type lineage A virus (Spearman rho, 0.5901 vs. 0.3827). However, the correlation between the anti-RBD or the anti-N IgG and the MN titer against the beta variant was poor. Conclusions: Currently available commercial antibody assays may not predict the level of neutralizing antibodies against the variants. A new generation of antibody tests specific for variants are required.

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Corticosteroids Contribute to Serious Adverse Events Following Live Attenuated Varicella Vaccination and Live Attenuated Zoster Vaccination

Vaccines ◽

10.3390/vaccines9010023 ◽

2021 ◽

Vol 9 (1) ◽

pp. 23

Author(s):

Nathan B. Price ◽

Charles Grose

Keyword(s):

Adverse Events ◽

Varicella Zoster Virus ◽

Case Reports ◽

Severe Infection ◽

Varicella Vaccination ◽

Wild Type ◽

Serious Adverse Events ◽

Live Virus ◽

Varicella Zoster ◽

Low Dosage

Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids contribute to serious adverse events (SAEs) following live varicella vaccination and live zoster vaccination. To this end, we examined multiple published reports of SAEs following varicella vaccination (VarivaxTM) and zoster vaccination (ZostavaxTM). We observed that five of eight viral SAEs following varicella vaccination, including two deaths, occurred in children receiving corticosteroids, while one of three fatal viral SAEs following live zoster vaccination occurred in an adult being treated with low-dosage prednisone. The latter death after live zoster vaccination occurred in a 70 year-old man with rheumatoid arthritis, being treated with prednisone 10 mg daily. Thus, corticosteroids contributed to more severe infectious complications in subjects immunized with each of the two live virus vaccines. Further, when we surveyed the rheumatology literature as well as individual case reports, we documented examples where daily dosages of 7.5–20 mg prednisone were associated with increased rates of severe wild-type varicella-zoster virus infections in children and adults.

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DMSA-scintigraphy in paediatrics: Is the evaluation of the geometric mean necessary for the calculation of the differential renal function?

Nuklearmedizin ◽

10.1055/s-0038-1625921 ◽

2001 ◽

Vol 40 (04) ◽

pp. 107-110 ◽

Cited By ~ 1

Author(s):

B. Roßmüller ◽

S. Alalp ◽

S. Fischer ◽

S. Dresel ◽

K. Hahn ◽

...

Keyword(s):

Renal Function ◽

Geometric Mean ◽

Region Of Interest ◽

Posterior View ◽

Renal Abnormality ◽

Anterior View ◽

Differential Renal Function ◽

The Mean ◽

The Right ◽

To Receive

SummaryFor assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimer-captosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. Aim of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. Methods: 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 ± 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256,300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr]. Results: The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p<0.01). The mean difference between the PFgeom and the PFdors was 1.5 ± 1.4%. A difference > 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference >5% did not show any renal abnormality. Conclusion: The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differntial renal function in orthotopic kidneys, so that in these cases the anterior view is not necesssary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.

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A multicenter prospective hospital-based cohort study on the efficacy and safety of pitavastatin.

Current Diabetes Reviews ◽

10.2174/1573399817666201228164243 ◽

2020 ◽

Vol 17 ◽

Author(s):

Abdullah Shehab ◽

Asim Ahmed Elnour ◽

Akshaya Srikanth Bhagavathula ◽

Joseph Pulavelil Kurian ◽

Gazi Hassan ◽

...

Keyword(s):

Cohort Study ◽

Adverse Events ◽

United Arab Emirates ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Efficacy And Safety ◽

Onset Diabetes ◽

The Mean ◽

New Onset

Aims: We aim to investigate the efficacy and safety of pitavastatin 4 mg in a population of people living in the United Arab Emirates (UAE). Background: Pitavastatin is a member of the HMG-CoA reductase inhibitors family which was approved for use in adult subjects with primary hyperlipidemia or mixed dyslipidemia. To date, no published studies have assessed the efficacy and safety of pitavastatin in the United Arab Emirates. Objective: The main objective of the current study was to investigate the efficacy and safety of pitavastatin in subjects with dyslipidemia for primary prevention of cardiovascular diseases based on total cardiovascular risk. Methods: This was a multicentre (four private hospitals) prospective cohort study to analyze data on the use of pitavastatin for dyslipidemia in adult outpatients in Abu Dhabi and Dubai emirates, United Arab Emirates. We have followed-up the clinical profiles of subjects in four hospitals for six-weeks during the period from June 2015 to June 2017. Efficacy was based on the evaluation of the mean (± standard deviation) change in low-density lipoprotein cholesterol between baseline and week six after the initiation of pitavastatin therapy. Safety was reported as the incidence of adverse events occurred with the use of pitavastatin and the development of new-onset diabetes. Results: A total of 400 subjects who were receiving pitavastatin 4 mg were included. The mean age of subjects was 50.7 ±10.8 years, of these 79.0% were males. At the baseline, the mean level of total cholesterol was 185.4 ±41.5 mg/dL, low density lipoprotein was 154.9 ±48.55 mg/dL, high-density lipoprotein cholesterol was 40.5 ±11.23 mg/dL and fasting blood glucose was 115.0 (±16.63) mg/dl. At the end of six weeks, low density lipoprotein levels significantly decreased to 112.09 ±41.90 mg/dl (standard mean difference [SMD] (-42.8%), 95% CI: -42.88 [-49.17 to -36.58] mg/dl, P <0.001), while high density lipoprotein levels improved (SMD, 95% CI: 1.77% [0.25 to 3.28] mg/dl, P <0.022). There were 55 subjects (13.7%) reported various adverse events such as myalgia (7.5%), sleep disorders (2.5%), and myopathy (2.2%). Furthermore, 4 (1.0%) have had developed new-onset diabetes post six-weeks of initiation of pitavastatin therapy. Conclusion: Pitavastatin 4 mg had howed robust efficacy in reducing LDL-C levels and improving HDL-C levels in subjects with dyslipidemias. The use of pitavastatin was associated with a low discontinuation rate, fewer adverse events, and very limited cases of new-onset diabetes.

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Association of Retained Fetal Membranes with Haematological Profile in Crossbred Cows

THE INDIAN JOURNAL OF VETERINARY SCIENCES AND BIOTECHNOLOGY ◽

10.21887/ijvsbt.v12i3.7101 ◽

2017 ◽

Vol 12 (3) ◽

Author(s):

K. Rokde ◽

S. Kumar ◽

A. Bhardwaz ◽

S. S. Mahour ◽

S. P. Nema ◽

...

Keyword(s):

Eosinophil Count ◽

Jugular Vein ◽

Dairy Farm ◽

Fetal Membranes ◽

Monocyte Count ◽

Blood Samples ◽

Mean Values ◽

Crossbred Cows ◽

Haematological Profile ◽

The Mean

This study was carried out on clinical cases of retained fetal membranes in crossbred cows presented at College Clinics and College dairy farm and from Villages in and around Mhow. The blood samples were collected from jugular vein just before 12 hr. postpartum and on 7th day postpartum. Haematological profile revealed that the mean values of haemoglobin, neutrophil and monocyte count after 12 hrs and 7th day postpartum were significantly lower and lymphocyte count was significantly higher in RFM cows (n=18) than normally calved cows (n=6). The differences in mean TLC, eosinophil and basophil counts were non-significant at 12 hrs postpartum, however on 7th day postpartum the TLC and eosinophil count were significantly higher and basophil count was non-significantly different in RFM cows than the normally calved cows.

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