When coronavirus disease 2019 (COVID-19) spread across the world, many countries were forced to enact costly and restrictive lockdowns, and it was not until the development and mass deployment of various vaccines that these ended. While several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were developed using conventional methods such as using attenuated forms of the virus, less traditional vaccines were also developed.
Study: SARS-CoV-2 antibody and T cell responses one year after COVID-19 and the booster effect of vaccination: a prospective cohort study. Image Credit: Kateryna Kon/Shutterstock
mRNA vaccines, for instance, the BNT162B2 vaccine, expose the vaccinee to a strand of mRNA encoding for a specific antigen and rely on the host’s cell machinery to translate it. Other manufacturers mounted viral surface proteins on nanoframes to allow local protein concentration to remain high, resulting in a more effective immune response. The vast majority of these vaccines targeted the spike protein, specifically the receptor-binding domain (RBD) within the S1 subunit of the spike protein. The RBD binds to angiotensin-converting enzyme 2 (ACE2), allowing viral cell entry, essential to SARS-CoV-2 pathogenicity.
In a study published in the Journal of Infection, researchers from the Netherlands Department of Medical Microbiology and Infection Control have been investigating the immune response in previously infected healthcare workers after they receive these vaccines.
The scientists only included healthcare workers (HCWs) who had tested positive from SARS-COV-2 using an RT-PCR test approximately one year previously and showed significant signs of seroconversion. Blood samples were obtained by venipuncture. Serum was isolated first, and the peripheral blood mononuclear cells were further isolated using paque density gradient separation. Commercially available ELISpot assays assessed T cell responses against SARS-CoV-2 antigens.
IgG antibodies were detected using quantitative ELISA assays. Statistical analysis of the final results used data expressed as medians with interquartile range. Mann-Whitney U tests were used to compare two groups, the Kruskal-Wallis test to compare over two groups. Spearman’s rank correlations assessed associations and strength of associations between groups.
The researchers included 55 SARS-CoV-2 seroconverted healthcare workers (HCW) in their final cohort. They were predominantly female and had a median age of 43. Nine of these reused vaccination, seven had already received one dose, and 16 had already received two doses.
The scientists stimulated the growth of peripheral blood mononuclear cells (PBMCs)isolated from 32 previously infected healthcare workers who had not been vaccinated. All of these showed at least weak responses to S1, and 53% showed strong/very strong anti-S1 responses. 93.8% and 90.6% showed at least weak responses to the nucleotide and membrane proteins, respectively, but a far lower proportion (28% and 25%) showed strong/very strong responses against these proteins. All healthcare workers showed T cell responses against SARS-CoV-2, and 84% showed a T cell response against all antigens tested. At one year post-infection, all HCWs showed anti-RBD IgG antibodies.
T cell responses rose significantly after the first vaccination dose, irrespective of the vaccine received. Median responses against the S1 subunit rose from 24 to 204. As expected, nucleotide and membrane-specific responses did not alter. Anti-RBD IgG concentrations also increased significantly, with the median concentration rising from 97 to 5930 IU/mL. Although the association between T-cell and IgG responses after the first vaccination was not significant, a strong statistically significant association was detected between the two after the second vaccination.
In healthcare workers who had been previously infected with SARS-CoV-2 and received full vaccination before the samples were collected, the researchers found that T cell and antibody response remained strong up to four months (the maximum duration tested) post-vaccination, and similar to the other HCWs, T cell reactivity remained significantly higher against the spike protein compared to the nucleocapsid or membrane proteins.
The authors highlight that their study shows that all previously infected healthcare workers showed a significant immune response, both specific S1 T cell and IgG, up to one year post-infection. These responses were boosted by even one vaccination. They also showed that vaccine-induced responses remained detectable up to four months post-infection. These findings are supported by many similar studies showing almost the same results, albeit in both healthcare workers and non-healthcare workers.
The researchers acknowledge that they did not examine the responses of neutralizing antibodies but explain that as many individuals received different vaccines, assessing this would have forced them to split their relatively small samples size even further, reducing the statistical significance of the study.
Mak, W. et al. (2021) “SARS-CoV-2 antibody and T cell responses one year after COVID-19 and the booster effect of vaccination: a prospective cohort study”, Journal of Infection. doi: 10.1016/j.jinf.2021.12.003. https://www.sciencedirect.com/science/article/pii/S0163445321005934#!
Unraveling How Strigoractone Hormone Regulates Massive Gene Networks Controlling Plant Growth
As sessile organisms, plants have to continually adapt their growth and architecture to the ever-changing environment. To do so, plants have evolved distinct molecular mechanisms to sense and respond to the environment and integrate the signals from outside with endogenous developmental programs.
New research from Nitzan Shabek’s laboratory at the UC Davis College of Biological Sciences, published in Nature Plants, unravels the underlying mechanism of protein targeting and destruction in a specific plant hormone signaling pathway.
Our lab aims at deciphering sensing mechanisms in plants and understanding how specific enzymes function can be regulated at the molecular levels. We have been studying a new plant hormone signal, strigolactone, that governs numerous processes of growth and development including branching and root architecture.”
Nitzan Shabek, assistant professor of biochemistry and structural biology, Department of Plant Biology
The work stems from a study by Shabek, published in Nature in 2018, unravelling molecular and structural changes in an enzyme, MAX2 (or D3) ubiquitin ligase. MAX2 was found in locked or unlocked forms that can recruit a strigolactone sensor, D14, and target for destruction a DNA transcriptional repressor complex, D53. Ubiquitins are small proteins, found in all eukaryotes, that “tag” other proteins for destruction within a cell.
To find the key to unlock MAX2 and to better understand its molecular dynamics in plants, postdoctoral fellows Lior Tal and Malathy Palayam, with junior specialist Aleczander Young, used an approach that integrated advanced structural biology, biochemistry, and plant genetics.
“We leveraged structure-guided approaches to systemically mutate MAX2 enzyme in Arabidopsis and created a MAX2 stuck in an unlocked form”, said Shabek, “some of these mutations were made by guiding CRISPR/Cas9 genome editing thus providing us a discovery platform to study and analyze the different signaling outputs and illuminate the role of MAX2 dynamics.”
They found that in the unlocked conformation, MAX2 can target the repressor proteins and biochemically decorate them with small ubiquitin proteins, tagging them for destruction. Removing these repressors allows other genes to be expressed – activating a massive gene network that governs shoot branching, root architecture, leaf senescence, and symbiosis with fungi, Shabek said.
Sending these repressors to the proteasome disposal complexes requires the enzyme to relock again. The team also showed that MAX2 not only target the repressors proteins, but once it is locked the strigolactone sensor itself gets destroyed, returning the system to its original state.
Finally, the study uncovered the key to the lock, an organic acid metabolite that can directly trigger the conformational switch.
“Beyond the implication in plants signaling, this is the first work that placed a primary metabolite as a direct new regulator of this type of ubiquitin ligase enzymes and will open new avenues of study in this direction,” Shabek said.
Additional coauthors on the paper are specialist Mily Ron and Professor Anne Britt, Department of Plant Biology. The study was supported by NSF CAREER and EAGER grants to Shabek. X-ray crystallography data was obtained at the Advanced Light Source, Lawrence Berkeley National Laboratory, a U.S. Department of Energy user facility.
Tal, L., et al. (2022) A conformational switch in the SCF-D3/MAX2 ubiquitin ligase facilitates strigolactone signalling. Nature Plants. doi.org/10.1038/s41477-022-01145-7.
Original Article: news-medical.net
UrFU Sociologists Identify Digital Fears Among Young People
Sociologists at the Ural Federal University (UrFU) have identified digital fears among young people. According to experts, these are additional fears that do not replace, but complement and reinforce traditional ones. They emerged against the background of uncertainty, the growth of forces beyond human control. Developed emotional intelligence, creativity, and the ability to collaborate help to overcome them.
In the study, sociologists interviewed 1,050 people aged 18-30. Respondents were asked to assess which digital risks concern them most. The study was launched in 2020 and the results were published in April 2022 in the Changing Societies & Personalities journal.
The first group of fears is influence and control. It touches on the problem of interference with privacy by technical means. This category is the most significant for young people: 55.8% are afraid of total control by means of video-surveillance and monitoring software on their mobile devices. 48.5% of respondents believe they are at risk of wiretapping, tracking content in social networks, and inability to keep correspondence secret.”
Natalia Antonova, Professor, Department of Applied Sociology, UrFU
45.8% of young people fear the manipulative influence of the media and an increase in fake news. At the same time, only 27.8% and 18.1% of respondents are concerned about microchipping and genetic manipulation, respectively. It is likely that these threats seem more controllable, both from the individual (through control of food choices, medical procedures, etc.) and from government programs, the researchers believe.
The second group of concerns is crime and security. Here young people are wary of illegal actions using digital technology.
“One of the main fears of 56% of young people is the security of personal data. This is related both to the growth of personal information in social networks and messengers, and to the growth of hacker attacks and viruses. 42.9% of young citizens are afraid of Internet fraudsters, and 25.8% are afraid of losing important information, including smashing their phones, not saving data, forgetting their passwords, or being without an Internet connection,” explains Sofia Abramova, Associate Professor at the Department of Applied Sociology at UrFU.
The third group of fears is based on changes in the way and pace of life, ways of interaction. Thus, 28.4% of respondents indicate a constant lack of time, the acceleration of communications, and worries about not being able to complete all tasks in time. Respondents are also concerned about the growth of online communications and communications with electronic systems (bots, autoresponders, product systems, etc.).
“As a result, 15.3% of young people raise problems related to increasing social distrust against the background of increasing dependence of human life and health on other people and electronic systems: in public transport, planes, elevators, medical intervention,” explains Sofia Abramova.
Respondents also fear the negative consequences of technological development. For example, 22.2% of young citizens fear the robotization of labor processes and the displacement of humans by robots. 14.6% speak directly about negative emotions in relation to the expansion of artificial intelligence.
The fifth type of fear is social inequality. Young people negatively assess the growth of inequality in access to information resources and technology, the exclusion of citizens from the economy depending on the level of digital competence and education, and age. As a result, they fear that benefits will be distributed more and more unequally, both among the inhabitants of the country and between countries.
“It is noteworthy that young people are simultaneously afraid of total surveillance via phone and afraid of being left without mobile devices. Fears shape the irrational behavior of the digital generation, entailing serious transformations in everyday life,” says Natalia Antonova.
Abramova, S.B., et al. (2022) Digital Fears Experienced by Young People in the Age of Technoscience. Changing Societies & Personalities. doi.org/10.15826/csp.2022.6.1.163.
Original Source: news-medical.net
Study demonstrates increased incidence of SARS-CoV-2 Omicron breakthrough infection in cancer patients
In a recently published article in the journal Cancer Cell, scientists have demonstrated the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients residing in Austria and Italy. The study reveals an induction in Omicron breakthrough infections in patients with hematologic and solid cancers.
Study: Enhanced SARS-CoV-2 breakthrough infections in patients with hematologic and solid cancers due to Omicron. Image Credit: Lightspring/Shutterstock
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19) pandemic, has been found to cause severe infections in immunocompromised patients, including cancer patients. Moreover, a relatively lower level of neutralizing antibodies in response to COVID-19 vaccines has also been observed in cancer patients, especially those receiving B cell-targeting therapies.
The emergence of SARS-CoV-2 variants with improved immune fitness, such as delta and Omicron variants, has caused a sharp increase in breakthrough infections even in fully vaccinated individuals. However, the vaccines still show high protective efficacy against severe and fatal infections. COVID-19 vaccines have shown acceptable efficacy against severe disease, even in Omicron-infected cancer patients. However, the isolation and quarantine measures associated with SARS-CoV-2 infection may impair the routine administration of anticancer therapy, which can reduce the survival prognosis in cancer patients.
In the current study, the scientists have assessed the incidence of SARS-CoV-2 infection in cancer patients throughout the pandemic.
The study included 3,959 cancer patients, of whom 77% had solid cancer, and 23% had hematologic cancer. About 69% of the patients did not receive any anticancer treatment at the time of COVID-19 vaccination. Regarding vaccine coverage, about 85% of the patients had received at least one vaccine dose, and 15% remained unvaccinated. The incidence of SARS-CoV-2 infection in these patients was assessed between February 2020 and 2022.
SARS-CoV-2 infection was detected in about 24% of the patients during the study period. During the delta-dominated wave, vaccine breakthrough infection was observed in 43% of the patients. In contrast, a significantly higher percentage of breakthrough infection (70%) was observed among the patients during the Omicron-dominated wave. During both delta and Omicron waves, cancer patients receiving systemic anticancer treatment showed a significantly higher percentage of breakthrough infection than those not receiving treatment (83% vs. 56%).
Regarding disease severity irrespective of vaccination status, a higher frequency of COVID-19-related hospitalization was observed during the delta wave compared to that during the Omicron wave. However, a relatively shorter duration of hospital stay was observed in vaccinated patients compared to that in unvaccinated patients. In addition, only 9% of patients with breakthrough infections were admitted to the intensive care unit (ICU). This highlights the protective efficacy of COVID-19 vaccines against severe disease.
Humoral immune response to vaccination
To determine vaccine-induced antibody response against delta and Omicron variants, the scientists measured blood levels of anti-delta and anti-Omicron spike receptor-binding domain (RBD) antibodies in a total of 78 cancer patients. In the analysis, they also included 25 healthcare workers as controls.
In response to vaccination, healthcare workers showed higher levels of total anti-spike antibodies compared to cancer patients. The lowest level of wildtype RBD-specific antibodies was observed in hematologic cancer patients receiving B cell-targeted treatment, followed by hematologic cancer patients not receiving B cell-targeted treatment and patients with solid tumors. A similar trend was observed for delta- and Omicron-specific spike RBD antibodies.
The serum samples collected from hematologic cancer patients without B cell-targeted treatment and solid tumor patients significantly inhibited the interaction between wildtype/delta RBD and angiotensin-converting enzyme 2 (ACE2; host cell receptor for viral entry). However, a significantly lower level of inhibition was observed for patients receiving B cell-targeted treatment. Importantly, a marked reduction in inhibition of Omicron RBD – ACE2 interaction was observed for all patients with solid tumors and hematologic cancer.
The study demonstrates an increased incidence of vaccine breakthrough infections but a reduced disease severity among patients with solid tumors and hematologic cancer during the Omicron wave compared to the delta wave.
The study also highlights that COVID-19 vaccine-induced antibody response is lower in cancer patients than in healthy individuals. The reduction in antibody response is highest among hematologic patients receiving B cell-targeted treatment. Overall, a significant impairment in vaccine-induced Omicron neutralization has been observed in cancer patients.
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