efficacy trials
Recently Published Documents


TOTAL DOCUMENTS

464
(FIVE YEARS 120)

H-INDEX

41
(FIVE YEARS 7)

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Wahib M. Atroosh ◽  
Yee-Ling Lau ◽  
Georges Snounou ◽  
Meram Azzani ◽  
Hesham M. Al-Mekhlafi

Abstract Background Genotyping of the three Plasmodium falciparum polymorphic genes, msp1, msp2 and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. However, the suitability of a particular gene is compromised in areas where its allelic variants distribution is significantly skewed, a phenomenon that might occur in isolated parasite populations or in areas of very low transmission. Moreover, observation of amplification bias has diminished the value of glurp as a marker. Methods The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR–RFLP protocol for genotyping of samples in drug efficacy clinical trials. The value of pfhrp2 was validated by side-by-side analyses of 5 admission-recrudescence sample pairs from Yemeni malaria patients. Results The outcome of the single pfhrp2 gene discrimination analysis has been found consistent with msp1, msp2 and glurp pool genotyping analysis for the differentiation of recrudescence from new infection. Conclusion The findings suggest that under the appropriate circumstances, pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene.


2021 ◽  
Author(s):  
Greg Guerin

Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).


2021 ◽  
Vol 12 ◽  
Author(s):  
Ria Lassaunière ◽  
Caroline T. Tiemessen

Receptors for the crystallisable fragment (Fc) of immunoglobulin (Ig) G, Fcγ receptors (FcγRs), link the humoral and cellular arms of the immune response, providing a diverse armamentarium of antimicrobial effector functions. Findings from HIV-1 vaccine efficacy trials highlight the need for further study of Fc-FcR interactions in understanding what may constitute vaccine-induced protective immunity. These include host genetic correlates identified within the low affinity Fcγ-receptor locus in three HIV-1 efficacy trials – VAX004, RV144, and HVTN 505. This perspective summarizes our present knowledge of FcγR genetics in the context of findings from HIV-1 efficacy trials, and draws on genetic variation described in other contexts, such as mother-to-child HIV-1 transmission and HIV-1 disease progression, to explore the potential contribution of FcγR variability in modulating different HIV-1 vaccine efficacy outcomes. Appreciating the complexity and the importance of the collective contribution of variation within the FCGR gene locus is important for understanding the role of FcγRs in protection against HIV-1 acquisition.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunda Huang ◽  
Oleg Borisov ◽  
Jia Jin Kee ◽  
Lindsay N. Carpp ◽  
Terri Wrin ◽  
...  

AbstractVaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization’s anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ghazanfar Abbas ◽  
Abdul Ghafar ◽  
John Hurley ◽  
Jenni Bauquier ◽  
Anne Beasley ◽  
...  

Abstract Background Cyathostomins are the most important and common parasitic nematodes of horses, with > 50 species known to occur worldwide. The frequent and indiscriminate use of anthelmintics has resulted in the development of anthelmintic resistance (AR) in horse nematodes. In this study we assessed the efficacy of commonly used anthelmintics against cyathostomins in Australian thoroughbred horses. Methods Two drug efficacy trials per farm were conducted on two thoroughbred horse farms in the state of Victoria, Australia. In the first trial, the horses on Farm A were treated with single and combinations of anthelmintics, including oxfendazole (OFZ), abamectin (ABM), abamectin and morantel (ABM + MOR), moxidectin (MOX) and oxfendazole and pyrantel (OFZ + PYR), at the recommended doses, whereas the horses on Farm B only received MOX, at the recommended dose. The faecal egg count reduction test (FECRT) was used to determine the efficacy and egg reappearance period (ERP) of anthelmintics. Based on the results of the first trial, the efficacies of MOX and a combination of ABM + MOR were reassessed to confirm their activities against cyathostomins. Results Of the five anthelmintic products tested on Farm A, resistance against OFZ, ABM and OFZ + PYR was found, with efficacies of − 41% (− 195% lower confidence limit [LCL]), 73% (60% LCL) and 82% (66% LCL) at 2 weeks post-treatment, respectively. The FECRT showed high efficacies of MOX and ABM + MOR (100%) at 2 week post-treatment and shortened ERPs for these anthelmintics (ABM + MOR: 4 weeks; MOX: 5 weeks). Resistance to MOX was found on Farm B, with a reduced efficacy of 90% (70% LCL) and 89% (82% LCL) at 2 weeks post-treatment in trials one and two, respectively. Conclusions This study provides the first evidence of MOX- and multidrug-resistant (ABM and combinations of anthelmintics) cyathostomins in Australia and indicates the need for continuous surveillance of the efficacy of currently effective anthelmintics and large-scale investigations to assess the ERP for various anthelmintics. Graphical Abstract


2021 ◽  
pp. ASN.2021060778
Author(s):  
Scott Sibbel ◽  
Katherine McKeon ◽  
Jiacong Luo ◽  
Karl Wendt ◽  
Adam Walker ◽  
...  

Background Patients on hemodialysis have an elevated risk for COVID-19 infection but were not included in efficacy trials of SARS-CoV-2 vaccines. Methods We conducted a retrospective, observational study to estimate the real-world effectiveness and immunogenicity of two mRNA SARS-CoV-2 vaccines in a large, representative population of adult hemodialysis patients in the United States. In separate, parallel analyses, patients who began a vaccination series with BNT162b2 or mRNA-1273 in January and February 2021 were matched with unvaccinated patients and followed after they completed the first of two doses. In a subset of patients, blood samples were collected approximately 28 days after the second dose and anti-SARS-CoV-2 immunoglobulin G was measured. Results A total of 12,169 patients received the BNT162b2 vaccine (matched with 44,377 unvaccinated controls); 23,037 patients received the mRNA-1273 vaccine (matched with 63,243 unvaccinated controls). Compared with controls, vaccinated patients' risk of being diagnosed with COVID-19 post-vaccination became progressively lower after the first dose (day 1) to days ≥43. Following a COVID-19 diagnosis, vaccinated patients were significantly less likely than unvaccinated patients to be hospitalized (for BNT162b2, 28.0% versus 43.4%; for mRNA-1273, 37.2% versus 45.6%) and significantly less likely to die (for BNT162b2, 4.0% versus 12.1%; for mRNA-1273, 5.6% versus 14.5%). Antibodies were detected in 98.1% (309/315) and 96.0% (308/321) of BNT162b2 and mRNA-1273 patients, respectively. Conclusions In patients on hemodialysis, vaccination with BNT162b2 or mRNA-12 was associated with a lower risk of COVID-19 diagnosis and significantly lower risk of hospitalization or death among those diagnosed with COVID-19. SARS-CoV-2 antibodies were detected in nearly all patients after vaccination. These findings support the use of these vaccines in this population.


2021 ◽  
Author(s):  
Jeffrey B Ulmer

DNA vaccines were first discovered more than 30 years ago. Because DNA vaccines result in antigen production in situ (i.e., mimic a virus infection), they elicit broad-based immune responses, including antibodies and T cells. Induction of protective immunity has been established in scores of animal models of infectious and non-infectious diseases. Hundreds of human clinical trials have been conducted demonstrating safety and, in many cases, antigen-specific immune responses. Several animal health vaccines based on DNA have been approved and are in use. Many DNA vaccines are in various stages of human clinical testing, including a few in phase 3 efficacy trials and the recent Emergency Use Authorization of a COVID-19 vaccine, but to date no DNA vaccines have been fully licensed for human use. DNA vaccines are thermostable and amenable to large-scale manufacturing at relatively low cost, hence well-suited for global use, particularly in the developing world. If potency in humans could be achieved, DNA vaccines would have the potential to be a radical innovation that could disrupt the vaccine industry.


Author(s):  
Suresh Kumar Srinivasamurthy ◽  
Laxminarayana Kurady Bairy

COVID-19 pandemic has affected the world in all its dimensions. With herd immunity being a distant and non-practical possibility, vaccination remains most tractable approach to reduce morbidity and mortality. Several early phase clinical trials have proved the immunogenicity of vaccines. The efficacy trials have shown reduction in chance of acquiring COVID-19 disease after vaccination. The vaccines approved for emergency use have reported efficacy above 50% thus making them important public health tool in controlling the pandemic. Nevertheless, several questions remain elusive such as whether these approved vaccines are effective against newer variants of the virus; whether vaccination prevents transmission of the virus in the community; clinical impact of vaccination on morbidity and mortality. This review aims to elucidate the status of vaccine candidates in advanced trials along with the vaccines, which have been granted emergency approvals. Further, we collate the data on vaccines efficacy phase 3 trials and their probability of efficacy against newer variants.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wee Yong Tan ◽  
Abdul Hanif Khan Yusof Khan ◽  
Mohd Naim Mohd Yaakob ◽  
Anna Misyail Abdul Rashid ◽  
Wei Chao Loh ◽  
...  

Abstract Background Transverse myelitis (TM) is a relatively uncommon condition, and vaccine-associated myelitis is even rarer. Concern regarding neurological complications following vaccination escalated following the report of TM during the safety and efficacy trials of the COVID-19 vaccine. Case presentation We report the first case of Longitudinal Extensive Transverse Myelitis (LETM) in Malaysia following administration of the chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine. A 25-year-old female presented with bilateral lower limb weakness and inability to walk with a sensory level up to T8 with absent visual symptoms. Urgent gadolinium-enhanced magnetic resonance imaging (MRI) of the spine showed long segment TM over the thoracic region. Cerebrospinal fluid autoantibodies for anti-aquaporin-4 and anti-myelin-oligodendrocyte were negative. A diagnosis of LETM following vaccination was made, and the patient was started on a high dose of intravenous methylprednisolone. The patient eventually made a recovery following treatment. Conclusion LETM is a rare but serious adverse reaction following vaccination. Previously reported cases showed an onset of symptoms between 10 to 14 days post-vaccination, suggesting a delayed immunogenic reaction. However, the incidence of myelitis in COVID-19 is much more common, far greater than the risk associated with vaccination.


2021 ◽  
Author(s):  
Yunda Huang ◽  
Oleg Borisov ◽  
Jia Jin Kee ◽  
Lindsay N. Carpp ◽  
Terri Wrin ◽  
...  

Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization's anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.


Sign in / Sign up

Export Citation Format

Share Document