Naive Individuals Research Articles

Size Preference of Live Fish Prey in the Pellet-Consuming Pikeperch

The production of pikeperch in a recirculation aquaculture system (RAS) is of growing importance. However, the use of combined technologies may also be justified, especially in countries with larger pond areas. However, this requires the most effective adaptation of pellet-consuming individuals to pond conditions. Foraging training, a form of environmental enrichment to compensate for the poor environment in hatchery rearing, can play a major role in this. The aim of our study was to investigate the prey size preference already observed in wild pikeperch, during prey capture by intensively reared naive individuals. We investigated predation success, latency, number of attempts during the process, and size distribution, in a total of 152 foraging trials of 38 pikeperch fingerlings (mean TL = 90.65 mm) at three different prey sizes (predator–prey length ratio (PPR): 0.11, 0.22, 0.33). Although predation on medium–large prey was more successful overall, it was achieved in more attempts and with greater latency. Small prey was captured with the fewest attempts. These results suggest that when calculating prey size in the foraging training of pikeperch, it is recommended to use a 0.11–0.22 PPR less than the optimal PPR described for wild individuals.

Social Learning of Innovations in Dynamic Predator-Prey Systems.

AbstractWe investigate the social transmission of innovations between predators. We focus on two classic predator-prey models. We assume that innovations increase predator attack rates or conversion efficiencies or that innovations reduce predator mortality or handling time. We find that a common outcome is the destabilization of the system. Destabilizing effects include increasing oscillations or limit cycles. Particularly, in more realistic systems (where prey are self-limiting and predators have a type II functional response), destabilization occurs because of overexploitation of the prey. Whenever instability increases the risk of extinction, innovations that benefit individual predators may not have positive long-term effects on predator populations. Additionally, instability could maintain behavioral variability among predators. Interestingly, when predator populations are low despite coexisting with prey populations near their carrying capacity, innovations that could help predators better exploit their prey are least likely to spread. Precisely how unlikely this is depends on whether naive individuals need to observe an informed individual interact with prey to learn the innovation. Our findings help illuminate how innovations could affect biological invasions, urban colonization, and the maintenance of behavioral polymorphisms.

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees.

Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses. Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS). Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigen-experienced ones. All vaccinees had increased galactosylated and sialylated anti-S IgG1. Both naive and antigen-experienced vaccinees showed relatively low macrophage activation potential, as expected, due to the low antibody levels for naive individuals with afucosylated IgG1, and low afucosylation levels for antigen-experienced individuals with high levels of anti-S. Afucosylation levels correlated with FUT8 expression in antigen-specific plasma cells in naive individuals. Interestingly, low fucosylation of anti-S IgG1 upon seroconversion correlated with high anti-S IgG levels after the second dose. Here, we show that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 responses in naive individuals. This observation warrants further studies to elucidate the clinical context in which potent afucosylated responses would be preferred. LSBR1721, 1908; ZonMW10430012010021, 09150161910033, 10430012010008; DFG398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.

Exploring Yersinia ruckeri (O1 Biotype 2) infection in three early life-stages of rainbow trout.

Enteric redmouth disease (ERM) caused by the enterobacterium Yersinia ruckeri poses a significant threat to salmonid aquaculture globally. Despite decades of experimental infection studies, key knowledge gaps remain regarding the onset of disease susceptibility and mechanisms of immunity during early developmental stages, undermining disease management efforts in all susceptible life-stages. In this study, a series of immersion challenges were conducted, challenging and re-challenging rainbow trout Oncorhynchus mykiss (Walbaum) at 7, 14 and 51 d post-hatch (dph; mean weights = 0.085, 0.1 and 2.0 g respectively) to high concentrations (1.72 × 107-1.1 × 108 CFU) of Y. ruckeri at 15°C. This study indicates the hitherto unknown initial point of susceptibility to infection as the time of first ingestion of exogenous food (14 dph), and shows that individuals surviving primary challenge at 14 dph are significantly more likely to survive re-challenge at 51 dph compared with naive individuals (hazard ratio = 1.446, p = 0.032). Other key findings include large variation in mortality between different development-stages, from 21.1% at 14 dph to 81.2% at 51 dph, and novel age-dependent symptoms not reported previously. Results from this study enhance our understanding of ERM in juvenile rainbow trout and inform the development of improved aquatic animal health management strategies, thereby contributing to the productivity and sustainability of salmonid aquaculture into the future.

Using pseudo-absence models to test for environmental selection in marine movement ecology: the importance of sample size and selection strength

BackgroundUnderstanding the selection of environmental conditions by animals requires knowledge of where they are, but also of where they could have been. Presence data can be accurately estimated by direct sampling, sightings, or through electronic tag deployments. However, absence data are harder to determine because absences are challenging to measure in an uncontrolled setting. To address this problem, ecologists have developed different methods for generating pseudo-absence data relying on theoretical movement models. These null models represent the movement of environmentally naive individuals, creating a set of locations that animals could have been if they were not exhibiting environmental selection.MethodsHere, we use four different kinds of null animal movement models—Brownian motion, Lévy walks, Correlated random walks, and Joint correlated random walks to test the ability and power of each of these null movement models to serve as appropriate animal absence models. We use Kolmogorov-Smirnov tests to detect environmental selection using two data sets, one of simulated animal tracks biased towards warmer sea surface temperatures, and one of 57 observed blue shark tracks of unknown sea surface temperature selection.ResultsThe four different types of movement models showed minimal difference in the ability to serve as appropriate null models for environmental selection studies. Selection strength and sample size were more important in detecting true environmental selection. We show that this method can suffer from high false positive rates, especially in the case where animals are not selecting for specific environments. We provide estimates of test accuracy at different sample sizes and selection strengths to avoid false positives when using this method.ConclusionWe show how movement models can be used to generate pseudo-absences and test for habitat selection in marine organisms. While this approach efficiently detects environmental selection in marine organisms, it cannot detect the underlying mechanisms driving this selection.

Correlation of Binding and Neutralizing Antibodies against SARS-CoV-2 Omicron Variant in Infection-Naïve and Convalescent BNT162b2 Recipients

In vaccine clinical trials, both binding antibody (bAb) levels and neutralization antibody (nAb) titers have been shown to be correlates of SARS-CoV-2 vaccine efficacy. We report a strong correlation bAb and nAb responses against the SARS-CoV-2 Omicron (BA.1) variant in infection-naïve and previously infected (convalescent) individuals after one and two doses of BNT162b2 vaccination. The vaccine-induced bAb levels against Omicron were significantly lower compared to previous variants of concern in both infection-naive and convalescent individuals, with the convalescent individuals showing significantly higher bAb compared to the naïve individuals at all timepoints. The finding that bAb highly correlated with nAb provides evidence for utilizing binding antibody assays as a surrogate for neutralizing antibody assays. Our data also revealed that after full vaccination, a higher percentage of individuals had undetectable Omicron nAb (58.6% in naive individuals, 7.4% in convalescent individuals) compared to the percentage of individuals who had negative Omicron bAb (0% in naive individuals, 0% in convalescent individuals). The discordance between bAb and nAb activities and the high degree of immune escape by Omicron may explain the high frequency of Omicron infections after vaccination.

Post-COVID-19 vaccine SARS-CoV-2 antibody investigation in healthcare professionals

Objectives: Main purpose of this study was evaluating inactive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine subsequent anti-S1 IgG feedback and the aspects involved in such reactions for professionals in healthcare (HCP) as the dominant risk group.Methods: Thirty-six HCPs with previous COVID-19 infection and 164 with no priors, 200 in total, who was working in the Ankara Public Health Molecular Diagnosis Laboratory were included. Main tool of identifying humoral immune response quantifably in serum samples which were obtained 28 days after administering each of two doses of vaccine was Roche Elecsys SARS-CoV-2 kit. Results: Average antibody levels of 164 negative HCPs were 15.82 ± 8.59 IU/mL and 26.042 ± 10.73 IU/mL while 36 positive HCPs demonstrated antibody responses as 66.083 ± 33.927 IU/mL and 90 ± 27.012 IU/mL 28 days after each of two doses of vaccine for both individual groups respectively. A statistically meaningful difference was found in antibody levels after two vaccine doses in both groups (p < 0.0001). The authors observed statistically higher average antibody levels after initial vaccine dosage in HCPs with infection than the antibody levels of naive individuals after second dose (p < 0.0001). Age, gender and vaccination feedback did not have a statistically meaningful disparity (p > 0.05). Conclusions: It was concluded that the average antibody level achieved after inital dose n HCPs with COVID-19 infection was surpassing the average antibody level obtained after the second dose in naive HCPs. The authors recommend further clinical researches on antibody levels and the extent of protection to prohibit COVID-19

Comparison of Gastric Cancer Screening Strategies between Helicobacter pylori-infected, -eradicated, and -naive Individuals

Comparison of Gastric Cancer Screening Strategies between Helicobacter pylori-infected, -eradicated, and -naive Individuals

Changes in mental health, wellbeing and personality following ayahuasca consumption: Results of a naturalistic longitudinal study.

Background: Naturalistic and placebo-controlled studies suggest ayahuasca, a potent psychedelic beverage originating from Indigenous Amazonian tradition, may improve mental health, alter personality structure, and reduce alcohol and drug intake. To better understand ayahuasca's therapeutic potential and to identify factors that influence therapeutic efficacy, we conducted a naturalistic, longitudinal study of facilitated ayahuasca consumption in naïve participants using a comprehensive battery of self-report questionnaires. Materials and Methods: Ayahuasca naive individuals registering for ayahuasca ceremonies were asked to complete a range of validated questionnaires assessing mental health, alcohol/cannabis use, relationships, personality, and connection to self and spirituality, prior to and 1month after attending an ayahuasca ceremony. Data for two mental health measures (the DASS-21 and PANAS) and acute subjective effects via the MEQ-30 were also assessed 7days post-ceremony. Repeated measures ANOVA were used to examine pre-to-post changes, and Pearson correlations explored predictors of improvement in outcomes. Results: Fifty-three attendees (32 women, 21 men) completed pre and post ayahuasca assessments with 55.6% of the sample reporting a complete mystical experience based on the MEQ-30. One-month post-ayahuasca, significant reductions were identified in depression, anxiety, stress, alcohol and cannabis use, body dissociation, accepting external influence, self-alienation, impulsivity, and negative affect/emotionality. Significant increases were identified in positive mood, self-efficacy, authentic living, extraversion, agreeableness, open-mindedness, spirituality, and satisfaction with relationships. While facets of the mystical experience held little predictive validity on outcome measures, baseline traits, particularly high negative emotionality and body dissociation, and low sense of self-efficacy, robustly predicted improvements in mental health and alcohol/cannabis use, and alterations in personality structure which are linked to better mental health. Discussion: This study suggests facilitated ayahuasca consumption in naïve participants may precipitate wide-ranging improvements in mental health, relationships, personality structure, and alcohol use. Associations between baseline traits and therapeutic improvements mark an important first step toward personalized, precision-based medicine and warrant randomized controlled trials to confirm and elaborate on these findings. Contribution Statement: Longitudinal, observational studies and randomized clinical control trials suggest ayahuasca may exert therapeutic effects on mental health and alcohol/cannabis use, and alter personality structure. However, it is unclear if improvements are diagnosis-specific and factors that predict therapeutic gains have yet to be extensively elucidated. This longitudinal, observational study examined the effects of facilitated ayahuasca consumption in naive participants on mental health, alcohol and substance use/abuse, personality traits, relationships, and connection to self and spirituality. We found wide-ranging improvements 1-month post-treatment across these domains, and identified baseline traits which predict pre-to-post changes on primary outcome measures. Improvements were not diagnostic-specific, suggesting ayahuasca may be generally efficacious. Personality traits, body dissociation, and self-efficacy were strong predictors of therapeutic improvements, marking an important first step toward personalized, precision-based medicine. Randomized controlled trials are warranted to confirm and elaborate on these findings.

A boost with SARS-CoV-2 BNT162b2 mRNA vaccine elicits strong humoral responses independently of the interval between the first two doses

Due to the recrudescence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections worldwide, mainly caused by the Omicron variant of concern (VOC) and its sub-lineages, several jurisdictions are administering an mRNA vaccine boost. Here, we analyze humoral responses induced after the second and third doses of an mRNA vaccine in naive and previously infected donors who received their second dose with an extended 16-week interval. We observe that the extended interval elicits robust humoral responses against VOCs, but this response is significantly diminished 4 months after the second dose. Administering a boost to these individuals brings back the humoral responses to the same levels obtained after the extended second dose. Interestingly, we observe that administering a boost to individuals that initially received a short 3- to 4-week regimen elicits humoral responses similar to those observed in the long interval regimen. Nevertheless, humoral responses elicited by the boost in naive individuals do not reach those present in previously infected vaccinated individuals.

They do not fear the unknown: Ancylus fluviatilis (Mollusca, Planorbidae) shows no predator avoidance behavior towards a novel invasive predator

Biological invasion is a strong threat to native biodiversity, with limnic systems being especially vulnerable due to historical separation and resulting prey naivety. The prey naivety hypothesis states that native species may not be able to recognize novel predators due to a lack of common evolutionary background and, therefore, become easy targets. In a laboratory experiment, we added cues of native European bullhead (Cottus gobio Linnaeus, 1758) and invasive round goby [Neogobius melanostomus (Pallas, 1814)] to Ancylus fluviatilis Müller, 1774 originating from two different populations within the same river (one naive, one experienced towards round goby) and compared their predator avoidance behavior. Individuals from both populations recognized cues from the known predator C. gobio and reduced their locomotive activity. To round goby cues, however, naive individuals did not respond, thereby supporting the prey naivety hypothesis. Experienced individuals, in contrast, reduced their activity, suggesting a learning effect due to the co-occurrence of invasive predator and prey. At fast moving invasion fronts of highly invasive species like N. melanostomus, prey naivety can, hence, enhance their negative impact on ecosystems. Behavioral adaptation of native species resulting in predator avoidance reactions could, therefore, play an important role in ecosystem resilience and temporal invasion dynamics.

Differential vaccine-induced kinetics of humoral and cellular immune responses in SARS-CoV-2 naive and convalescent health care workers.

Effective vaccination is a key element in the exit strategy from the current severe acute respiratory syndrome- CoV coronavirus-2 (SARS-CoV-2) pandemic, and may also offer protection against severe disease from future variants of concern. Here we prospectively monitored T- cell responses over time, using ELISpot interferon-γ (INF-y) release assays, and B- cell responses, using serological tests, after vaccination and booster with BioNTech/Pfizer mRNA (Pfizer) and Janssen vector (Janssen/Johnson & Johnson) vaccines in hospital health care workers. Vaccine recipients were divided into seropositive and seronegative individuals at baseline, in order to determine the effect of natural immunity on vaccine-induced immune kinetics.We found that convalescent individuals mounted higher spike-specific INF-y-secreting T cell responses and B- cell-mediated IgG responses, after receiving the Janssen vaccine or the first dose of the Pfizer vaccine. IgG levels corresponded to the virus neutralisation capacity as measured by VNT assay. At 8 months post vaccination, spike-specific cellular immunity waned to low levels in individuals with or without prior natural immunity, whereas waning of humoral immunity occurred predominantly in naive individuals. The booster shot effectively re-induced both cellular and humoral immune responses.To conclude, our data supports the implemented single-dose mRNA booster strategy employed in the Netherlands. Furthermore, the level of pre-existing natural immunity may be factored into determining the optimal time window between future booster vaccines.

Neutralizing immunity against SARS-CoV-2 Omicron BA.1 by infection and vaccination

SummaryThe emergence of the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant has raised questions regarding resistance to neutralizing antibodies elicited by natural infection or immunization. We examined the neutralization activity of sera collected from previously SARS-CoV-2-infected individuals and SARS-CoV-2 naive individuals who received BBIBP-CorV or CoronaVac to BA.1 and the earlier variants Alpha, Beta, and Delta. Both sera from convalescent patients over three months after infection and two-dose BBIBP-CorV or CoronaVac vaccine recipients barely inhibited BA.1, less effectively neutralized Beta and Delta, and moderately neutralized Alpha. However, administering a single dose of BBIBP-CorV or CoronaVac in previously infected individuals or a third dose booster vaccination of BBIBP-CorV or CoronaVac in previously vaccinated individuals enhances neutralizing activity against BA.1 and other variants, albeit with a lower antibody titer for BA.1. Our data suggest that a booster vaccination is important to broaden neutralizing antibody responses against the variants.

SARS-CoV-2 vaccine-induced antibody and Tcell response in SARS-CoV-1 survivors.

Preexisting immunity cross-reactive to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in SARS-CoV-1 survivors suggests that a coronavirus disease 2019 vaccine may boost such preexisting cross-reactive memory T cells. We measure SARS-CoV-2 and SARS-CoV-1 spike-specific neutralizing antibody and T cell responses in a single dose of Ad5-nCoV-immunized SARS-CoV-1 survivors 6 months after vaccination. Compared with Ad5-nCoV-immunized naive healthy individuals (NHIs), vaccination of Ad5-nCoV in SARS-CoV-1 survivors boosts the antibody response against SARS-CoV-1 but induces a limited neutralizing antibody that is capable of neutralizing SARS-CoV-2 variants of concern, and nearly all serum samples lose neutralization to Omicron subvariants. Immunized SARS-CoV-1 survivors produce a T cell response to SARS-CoV-2 comparable with that of Ad5-nCoV-immunized NHIs. However, a robust cross-reactive T cell response to SARS-CoV-1 is identified in immunized SARS-CoV-1 survivors compared with Ad5-nCoV-immunized NHIs. These findings suggest that vaccination with Ad5-nCoV elicits a stronger neutralizing antibody and cross-reactive T cell responses against SARS-CoV-1 in SARS-CoV-1 survivors.

Opioid usage differs significantly following ureteroscopy and shockwave lithotripsy, while development of long-term usage is positively correlated with total days' supply and total MME supplied.

This study evaluated possible predictors of long-term opioid usage among patients with ureteric stones who received ureteroscopy (URS) or shockwave lithotripsy (SWL). We also assessed opioid usage characteristics of URS and SWL recipients. This retrospective study used IQVIA PharMetrics® Plus for Academicsadministrative claims database from years 2006-2020 to identify patients with a diagnosis of kidney or ureteral stones who were treated with either SWL or URS. We performed unadjusted bivariate analyses to compare opioid use characteristics of URS and SWL recipients, and performed logistic regression to determine demographic and clinical factors associated with becoming a long-term opioid user. The study population consisted of opioid naive individuals having a diagnosis of a kidney stone who underwent URS (N = 9407) or SWL (N = 4894). About 6.7% (N = 964) of study subjects were long-term opioid users. Unadjusted bivariate associations showed that compared to non-long-term opioid users, long-term opioid users had significantly greater total days' supply, total morphine milliequivalents (MME) supplied, and claims per month. A similar trend was observed for URS (vs. SWL) recipients. However, compared to SWL recipients, URS recipients had 14.3% (1.2-25.6%; p = 0.034) lower odds of becoming long-term users. Total days' supply (OR: 1.041 (95% CI 1.030-1.052; p < 0.001) and total MME supplied (OR 1.001 (95% CI 1.000-1.001; p < 0.001) were significantly associated with long-term usage. Higher total days' supply and total MME supplied as well as SWL were identified as risk factors for becoming long-term opioid users.

Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study.

SummaryBackgroundThe protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised.MethodsIn a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2nd and 3rd vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1.FindingsAmong the 38 elderly individuals recruited to the cohort study between November 23rd, 2020 and April 29th, 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively.InterpretationThis study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity.FundingInstitut Pasteur, Fondation pour la Recherche Médicale (FRM), European Health Emergency Preparedness and Response Authority (HERA), Agence nationale de recherches sur le sida et les hépatites virales – Maladies Infectieuses Emergentes (ANRS-MIE), Agence nationale de la recherche (ANR), Assistance Publique des Hôpitaux de Paris (AP-HP) and Fondation de France.

Cascading indirect genetic effects in a clonal vertebrate.

Understanding how individual differences arise and how their effects propagate through groups are fundamental issues in biology. Individual differences can arise from indirect genetic effects (IGE): genetically based variation in the conspecifics with which an individual interacts. Using a clonal species, the Amazon molly (Poecilia formosa), we test the hypothesis that IGE can propagate to influence phenotypes of the individuals that do not experience them firsthand. We tested this by exposing genetically identical Amazon mollies to conspecific social partners of different clonal lineages, and then moving these focal individuals to new social groups in which they were the only member to have experienced the IGE. We found that genetically different social environments resulted in the focal animals experiencing different levels of aggression, and that these IGE carried over into new social groups to influence the behaviour of naive individuals. These data reveal that IGE can cascade beyond the individuals that experience them. Opportunity for cascading IGE is ubiquitous, especially in species with long-distance dispersal or fission-fusion group dynamics. Cascades could amplify (or mitigate) the effects of IGE on trait variation and on evolutionary trajectories. Expansion of the IGE framework to include cascading and other types of carry-over effects will therefore improve understanding of individual variation and social evolution and allow more accurate prediction of population response to changing environments.

MRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

SummaryIndividuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.

Kinetics and Persistence of the Cellular and Humoral Immune Responses to BNT162b2 mRNA Vaccine in SARS-CoV-2-Naive and -Experienced Subjects: Impact of Booster Dose and Breakthrough Infections.

BackgroundUnderstanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the cellular and humoral immune response in healthcare workers up to 12 months after the initial vaccination, with one additional boosting dose between 6 and 12 months.MethodsThis prospective study enrolled 208 healthcare workers (HCWs) from the Liège University Hospital (CHU) of Liège in Belgium. Participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2) and a booster dose 6-12 months later. Fifty participants were SARS-CoV-2 experienced and 158 were naïve before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3), 6 months (T4) and 12 months (T5) after the second dose. Between T4 and T5, participants also got the third boosting vaccine dose. A total of 1145 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies, using the DiaSorin LIAISON SARS-CoV-2 Trimeric S IgG assay, and for anti-Nucleocapsid antibodies, using Elecsys anti-SARS-CoV-2 assay​​. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization assay. Cell-mediated immune response was evaluated at T4 and T5 on 80 and 55 participants, respectively, by measuring the secretion of IFN-γ on peripheral blood lymphocytes using the QuantiFERON Human IFN-γ SARS-CoV-2, from Qiagen. We analyzed separately the naïve and experienced participants.FindingsWe found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced HCWs compared to naïve HCWs at all time points analyzed except the one after boosting dose. Cellular immune response was also higher in experienced HCWs six months following vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative association between age and persistence of humoral response. The booster dose induced an increase in humoral and cellular immune responses, particularly in naive individuals. Breakthrough infections resulted in higher cellular and humoral responses after the booster dose.ConclusionsOur data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. The benefit of the booster dose was greater in naive individuals. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses.

Thromboembolism and bleeding in patients with atrial fibrillation and liver disease – A nationwide register-based cohort study: Thromboembolism and bleeding in liver disease

BackgroundBalancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging. PurposeTo examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF. MethodsDanish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA2DS2-VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease. ResultsFour hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1–2 (2–3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22–2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45–0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status. ConclusionOral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease.