Naive Individuals Research Articles

Desert Ant (Melophorus bagoti) Dumpers Learn from Experience to Improve Waste Disposal and Show Spatial Fidelity.

The Central Australian red honey-pot ant Melophorus bagoti maintains non-cryptic ground-nesting colonies in the semi-desert habitat, performing all the activities outside the nest during the hottest periods of summer days. These ants rely on path integration and view-based cues for navigation. They manage waste by taking out unwanted food, dead nestmates, and some other wastes, typically depositing such items at distances > 5 m from the nest entrance, a process called dumping. We found that over multiple runs, dumpers headed in the same general direction, showing sector fidelity. Experienced ants dumped waste more efficiently than naive ants. Naive individuals, lacking prior exposure to the outdoor environment around the nest, exhibited much scanning and meandering during waste disposal. In contrast, experienced ants dumped waste with straighter paths and a notable absence of scanning behaviour. Furthermore, experienced dumpers deposited waste at a greater distance from the nest compared to their naive counterparts. We also investigated the navigational knowledge of naive and experienced dumpers by displacing them 2 m away from the nest. Naive dumpers were not oriented towards the nest in their initial trajectory at any of the 2 m test locations, whereas experienced dumpers were oriented towards the nest at all test locations. Naive dumpers were nest-oriented as a group, however, at the test location nearest to where they dumped their waste. These differences suggest that in red honey ants, learning supports waste disposal, with dumping being refined through experience. Dumpers gain greater spatial knowledge through repeated runs outside the nest, contributing to successful homing behaviour.

Lack of Resistance Mutations to the Novel HIV-1 Capsid Inhibitor Lenacapavir Among People Living with HIV in Guangdong, China.

The capsid inhibitor (CAI) lenacapavir (LEN) was approved for use in 2022, yet there are few reports about its drug resistance mutations (DRMs) and sensitivity. To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China. A total of 1035 individuals with HIV-1 infection, including 660highly Active Anti-Retroviral Therapy (HAART) naive individuals and 375hAART experienced individuals whose protease (PR)/ reverse transcriptase (RT) fragments were amplified successfully during drug resistance surveillance between October 2021 and December 2023, were randomly included in this study. The entire HIV-1 gag gene was amplified from plasma in LEN-naive individuals with or without antiretroviral therapy. The epidemiological and demographic information of the enrolled individuals were collected. The Stanford HIV Drug Resistance Database HIVdb program for Capsid was used to interpret the CAI DRMs and the LEN susceptibility. Among 1035 samples, 805 gag sequences were amplified, sequenced and assembled successfully from 518hAART drugs naive individuals and 287hAART drugs experienced individuals. Among them, 0.50% (4/805) carried at least one CAI DRM, of which 0.19% (1/518) from HAART naive individuals and 1.05% (3/287) from HAART experienced individuals. Among the individuals with CAI DRMs, two patients carried CAI major mutations (Q67H) conferring intermediate resistance to LEN and two patients carried CAI accessory mutation (T107A) conferring low level resistance to LEN. Extremely low prevalence of CAI DRMs was detected among people living with HIV (PLWH) in Guangdong, China. Our observations indicate that LEN application may be promising when used in clinical practice in China. Before the administration of LEN, there is no need to consider detecting CAI mutations in PLWH through DRM examination for the time being.

Financial education as a complement to public pensions: the case of naive individuals

Financial education as a complement to public pensions: the case of naive individuals

The Molecular and Biological Patterns Underlying Sustained SARS-CoV-2 Circulation in the Human Population

For four years, SARS-CoV-2, the etiological agent of COVID-19, has been circulating among humans. By the end of the second year, an absence of immunologically naive individuals was observed, attributable to extensive immunization efforts and natural viral exposure. This study focuses on delineating the molecular and biological patterns that facilitate the persistence of SARS-CoV-2, thereby informing predictions on the epidemiological trajectory of COVID-19 toward refining pandemic countermeasures. The aim of this study was to describe the molecular biological patterns identified that contribute to the persistence of the virus in the human population. For over three years since the beginning of the COVID-19 pandemic, molecular genetic monitoring of SARS-CoV-2 has been conducted, which included the collection of nasopharyngeal swabs from infected individuals, assessment of viral load, and subsequent whole-genome sequencing. We discerned dominant genetic lineages correlated with rising disease incidence. We scrutinized amino acid substitutions across SARS-CoV-2 proteins and quantified viral loads in swab samples from patients with emerging COVID-19 variants. Our findings suggest a model of viral persistence characterized by 1) periodic serotype shifts causing substantial diminutions in serum virus-neutralizing activity (> 10-fold), 2) serotype-specific accrual of point mutations in the receptor-binding domain (RBD) to modestly circumvent neutralizing antibodies and enhance receptor affinity, and 3) a gradually increasing amount of virus being shed in mucosal surfaces within a single serotype. This model aptly accounts for the dynamics of COVID-19 incidence in Moscow. For a comprehensive understanding of these dynamics, acquiring population-level data on immune tension and antibody neutralization relative to genetic lineage compositions is essential.

Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.

Respect and anxiety: Guns as ambiguous symbols for criminally involved youth in Sweden

Youth gun violence has surged in Sweden recently. Quantitative studies have described the prevalence and geographical locations of gun violence, but little research has examined how perpetrators and victims themselves experience and make sense of guns. This article draws on ethnographic interviews with young men who have firsthand experience of gun violence in a criminal context. Drawing on narrative analysis, it shows that guns are given multifaceted significance by the research participants and featured both implicitly and explicitly in their stories of their everyday lives. Guns were portrayed ambiguously, as a drastic means of self-protection that could also be used to remedy strained relations. Moreover, guns were presented as a means to build a reputation and gain respect. Gun violence was also charged with a range of emotions, notably hate, fear, and numbness. Even though young men considered that obtaining and using a gun could be justified, they also lamented the shootings, especially those committed by younger, putatively naive individuals.

Affinity-independent memory B cell origin of the early antibody-secreting cell response in naive individuals upon SARS-CoV-2 vaccination

Memory B cells (MBCs) formed over the individual's lifetime constitute nearly half of the circulating B cell repertoire in humans. These pre-existing MBCs dominate recall responses to their cognate antigens, but how they respond to recognition of novel antigens is not well understood. Here, we tracked the origin and followed the differentiation paths of MBCs in the early anti-spike (S)response to mRNA vaccination in SARS-CoV-2-naive individuals on single-cell and monoclonal antibody levels. Pre-existing, highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody-secreting cells (ASCs). By contrast, and despite similar levels of S reactivity, naive B cells showed strong signs of antibody affinity maturation before differentiating into MBCs and ASCs. Thus, pre-existing human MBCs differentiate into ASCs in response to novel antigens, but the quality of the humoral and cellular anti-S response improved through the clonal selection and affinity maturation of naive precursors.

Exploiting floral signals: Olfactory crypsis and visual attraction in crab spider predatory strategies

AbstractPredation exerts a profound influence on the evolution of camouflage and detection abilities in both predators and prey. For instance, flower‐visiting spiders need to ensure their concealment when ambushing on flowers, which compels pollinators to check any spider cues cautiously before landing. Although numerous studies have examined the visual camouflage of spiders deceiving bees, little is known regarding whether spiders also employ olfactory camouflage. Additionally, the detection of spiders by dipteran insects is often overlooked, despite them being major non‐bee pollinators. Here, we explored the detection ability of dipteran pollinators and the crypsis skill of spiders from both olfactory and vision perspectives using the housefly Musca domestica L. (Diptera: Muscidae) as prey, the crab spider Ebrechtella tricuspidata (Fabricius) (Araneae: Thomisidae) as predators and chamomile Matricaria recutita L. (Asteraceae) as substrates. Our olfactory experiments revealed that experienced houseflies could respond to and avoid spider odour. However, this response did not appear to be innate, as naive individuals showed no aversion. Moreover, experienced houseflies did not have any avoidance behaviours to the mixed odours of spider and flower, indicating that spiders achieved olfactory crypsis utilizing floral scent. Our vision experiments and visual modelling demonstrated that houseflies could detect spiders positioned on flower. Surprisingly, instead of avoiding them, houseflies exhibited a preference for flowers occupied by female spiders, suggesting the attractive nature of female spider colouration. This paper provides evidence for the first time that crab spiders use floral scent to achieve olfactory crypsis and proposes a potential yellow‐signalling mechanism for crab spiders to attract insects.

The evaluation of the expression pattern of the LncRNAs (AP006621.9, RP3-323A16.1, and HOXC-AS3), and their target genes (MTOR, TNF-α and TRAF6) in PBMC of long-term non-progressors and HIV-1 infected naive individuals

A selected group of individuals with HIV, known as Elite Controllers (ECs), are able to regulate the replication of the virus in their bodies without needing antiviral drugs. LncRNAs, a type of RNA, are essential components of the chain responsible for controlling transcription in the case of HIV. Researchers suggest that components such as mTOR, TNF-α, and TRAF6 are also actively involved in keeping the HIV infection under control. In this study, a bioinformatic approach was used to determine which long non-coding RNAs (lncRNAs) could bind to mTOR, TNF-α, and TRAF6. The expression levels of these three lncRNAs and their designated targets were then observed in 14 ECs, 45 HIV-positive patients, and 45 healthy control subjects. The results indicated that the expression of TNF-α and TRAF6 were notably greater in the ECs group than in the HIV-positive group (P < 0.0001). Moreover, lnc-HOXC-AS3 was strongly overexpressed in the ECs group when compared to the HIV-positive group (P < 0.0001). By contrast, no important variations were seen in the levels of RP3-323A16.1, and AP006621.9 between the two study groups. Investigations of the receiver-operating characteristic (ROC) curve determined that lnc-HOXC-AS3, TNF-α and TRAF6 had an AUC of 0.92, 0.91, and 0.86 respectively, suggesting that they could be used as feasible biomarkers for separating ECs from HIV-1 positive samples. A significant negative correlation was found between HOXC-AS3 with mTOR and between AP006621.9 with TNF-α and TRAF6 in the HIV-positive group. The expression patterns of the chosen factors, paired with the evidence gained from the ROC curve, suggests that these factors could play an important part in controlling HIV infection, and may be used to detect ECs from HIV positive samples.

Repeated Omicron infection dampens immune imprinting from previous vaccination and induces broad neutralizing antibodies against Omicron sub-variants

ObjectiveSimilar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting has been found to limit the performance of updated vaccines based on the emerging variants of SARS-CoV-2. We aimed to investigate whether repeated exposure to Omicron variant could reduce the immune imprinting from previous vaccination. MethodsA total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. ResultsNeutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50>500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants, both in the vaccine naive and vaccine experienced individuals. ConclusionsOur results demonstrate that repeated Omicron infection dampens immune imprinting from vaccination with WT SARS-CoV-2 and induces broad neutralizing profiles against Omicron sub-variants.

Complement-dependent virion lysis mediated by dengue-Zika virus cross-reactive antibodies correlates with protection from severe dengue disease.

Primary infection with one of four dengue virus serotypes (DENV1-4) may generate antibodies that protect or enhance subsequent secondary heterotypic infections. However, the characteristics of heterotypic cross-reactive antibodies associated with protection from symptomatic infection and severe disease are not well-defined. We selected plasma samples collected before a secondary DENV heterotypic infection that was classified either as dengue fever (DF, n = 31) or dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS, n = 33) from our longstanding pediatric cohort in Nicaragua. We screened various antibody properties to determine the features correlated with protection from DHF/DSS. Protection was associated with high levels of binding of various antibody isotypes, IgG subclasses and effector functions, including antibody-dependent complement deposition, ADCD. Although the samples were derived from DENV-exposed, Zika virus (ZIKV)-naïve individuals, the protective ADCD association was stronger when assays were conducted with recombinant ZIKV antigens. Further, we showed that a complement-mediated virion lysis (virolysis) assay conducted with ZIKV virions was strongly associated with protection, a finding reproduced in an independent sample set collected prior to secondary heterotypic inapparent versus symptomatic DENV infection. Virolysis was the main antibody feature correlated with protection from DHF/DSS and severe symptoms, such as thrombocytopenia, hemorrhagic manifestations, and plasma leakage. Hence, anti-DENV antibodies that cross-react with ZIKV, target virion-associated epitopes, and mediate complement-dependent virolysis are correlated with protection from secondary symptomatic DENV infection and DHF/DSS. These findings may support the rational design and evaluation of dengue vaccines and development of therapeutics.

Development and validation of the mindful eating scale (mind-eat scale) in a general population

BackgroundMindful eating is a concept that is increasingly being used to promote healthy eating. Observational studies have suggested associations with healthier eating behaviors, lower weight status, and favorable cardiovascular biomarkers. However, existing scales assessing mindful eating have some limitations. Our study aimed to develop and validate a scale assessing the level of mindful eating in a general population. MethodsThe Mind-Eat Scale was developed in four main steps: 1. Generating an initial item pool covering all aspects of mindful eating; 2. Reviewing items with experts and naive individuals; 3. Administering the scale to a large and representative sample from the NutriNet-Santé cohort (N = 3102); 4. Conducting psychometric analyses. Construct validity was assessed using exploratory (EFA) (N1 = 1302) and confirmatory (CFA) (N2 = 1302, N3 = 498) factor analyses. Content, discriminant, convergent, and divergent validity, internal consistency, and test-retest reliability were examined. ResultsThe initial pool of 95 items was refined to 24 items using EFA. The EFA highlighted six dimensions: Awareness, Non-reactivity, Openness, Gratitude, Non-judgement, and Hunger/Satiety, consisting of four items per dimension. CFAs showed a good fit for first and second-order models. Adequate content validity was confirmed. Discriminant, convergent, and divergent validity were supported by significant differences between subgroups of individuals, and correlations with eating behaviors and psychological well-being scales. The Mind-Eat Scale showed good reliability for all six dimensions, with high McDonald's ω and adequate intraclass correlation coefficients (ICC). ConclusionsThis study validated the first tool assessing a total mindful eating score and its sub-dimensions in a general population. This scale can be an asset for clinical and epidemiological research on dietary behavior and related chronic diseases.

Understanding the Role of Naive Learners in Cultural Change.

AbstractA change to a population's social network is a change to the substrate of cultural transmission, affecting behavioral diversity and adaptive cultural evolution. While features of network structure such as population size and density have been well studied, less is understood about the influence of social processes such as population turnover-or the repeated replacement of individuals by naive individuals. Experimental data have led to the hypothesis that naive learners can drive cultural evolution by better assessing the relative value of behaviors, although this hypothesis has been expressed only verbally. We conducted a formal exploration of this hypothesis using a generative model that concurrently simulated its two key ingredients: social transmission and reinforcement learning. We simulated competition between high- and low-reward behaviors while varying turnover magnitude and tempo. Variation in turnover influenced changes in the distributions of cultural behaviors, irrespective of initial knowledge-state conditions. We found optimal turnover regimes that amplified the production of higher reward behaviors through two key mechanisms: repertoire composition and enhanced valuation by agents that knew both behaviors. These effects depended on network and learning parameters. Our model provides formal theoretical support for, and predictions about, the hypothesis that naive learners can shape cultural change through their enhanced sampling ability. By moving from experimental data to theory, we illuminate an underdiscussed generative process that can lead to changes in cultural behavior, arising from an interaction between social dynamics and learning.

Pretreatment HIV-1 Resistance in Argentina: Results from the Second Surveillance Study Following World Health Organization Guidelines (2019).

More than 62,000 individuals are currently on antiretroviral treatment within the public health system in Argentina. In 2019, more than 50% of people on ART received non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this context, the second nationwide HIV-1 pretreatment drug resistance surveillance study was carried out between April and December 2019 to assess the prevalence of HIV-1 drug resistance in Argentina using the World Health Organization guidelines. This was a nationwide cross-sectional study enrolling consecutive 18-year-old and older individuals starting ARVs at 19 ART-dispensing centers. This allowed us to estimate a point prevalence rate of resistance-associated mutations (RAMs) with a confidence interval (CI) of 5% (for the total population and for those without antiretroviral exposure). Four-hundred forty-seven individuals were included in the study. The prevalence of mutations associated with resistance was detected in 27.7% (95% CI 25.6-34.9%) of the population. For NNRTI, it was 19.6% (95% CI 16.3-24.5%), for integrase strand transfer inhibitor (INSTI) 6.1% (95% CI 6.1-11.9%), for nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) 3% (95% CI 1.9-5.9%), and for protease inhibitors 1.5% (95% CI 0.7-3.6%). Naive individuals had variants of resistance to NRTIs in 16.8% (95% CI 12.8-21.4) and 5.7% (95% CI 2.9-15.9) to INSTI. For experienced individuals, the prevalence of variants associated with resistance was 30.38% (95% CI 20.8-42.2) for NRTIs and 7.7% (95% CI 2.9-15.9) for INSTI. This study shows an increase in the frequency of nonpolymorphic RAMs associated with resistance to NNRTI. This study generates the framework of evidence that supports the use of schemes based on high genetic barrier integrase inhibitors as the first line of treatment and the need for the use of resistance test before prescribing schemes based on NNRTI. We report for the first time the presence of a natural polymorphism associated with the most prevalent recombinant viral form in Argentina and the presence of a mutation linked to first-line integrase inhibitors such as raltegravir.

Early host immune responses in a human organoid-derived gallbladder monolayer to Salmonella Typhi strains from patients with acute and chronic infections: a comparative analysis.

Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly. Interestingly, if not antibiotic-treated, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma. Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients would differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer model, and S. Typhi strains derived from acutely and chronically infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate host mitogen-activated protein kinase (MAPK) and S6 transcription factors. These variations might be attributed to differential cytokine signaling, predominantly via TNF-α and IL-6 production and appear to be influenced by the duration the isolate was subjected to selective pressures in the gallbladder. These findings represent a significant leap in understanding the complexities behind chronic S. Typhi infections in the gallbladder and may uncover potential intervention targets.

Immigration delays but does not prevent adaptation following environmental change: experimental evidence.

In today's rapidly changing world, it is critical to examine how animal populations will respond to severe environmental change. Following events such as pollution or deforestation that cause populations to decline, extinction will occur unless populations can adapt in response to natural selection, a process called evolutionary rescue. Theory predicts that immigration can delay extinction and provide novel genetic material that can prevent inbreeding depression and facilitate adaptation. However, when potential source populations have not experienced the new environment before (i.e., are naive), immigration can counteract selection and constrain adaptation. This study evaluated the effects of immigration of naive individuals on evolutionary rescue using the red flour beetle, Tribolium castaneum, as a model system. Small populations were exposed to a challenging environment, and three immigration rates (zero, one, or five migrants per generation) were implemented with migrants from a benign environment. Following an initial decline in population size across all treatments, populations receiving no immigration gained a higher growth rate one generation earlier than those with immigration, illustrating the constraining effects of immigration on adaptation. After seven generations, a reciprocal transplant experiment found evidence for adaptation regardless of immigration rate. Thus, while the immigration of naive individuals briefly delayed adaptation, it did not increase extinction risk or prevent adaptation following environmental change.

Intradermal delivery of the third dose of the mRNA-1273 SARS-CoV-2 vaccine: safety and immunogenicity of a fractional booster dose

ObjectivesThe aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. MethodsCOVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. ResultsIn January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. DiscussionIntradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness.

SARS-CoV-2-infection- and vaccine-induced antibody responses are long lasting with an initial waning phase followed by a stabilization phase

It is thought that mRNA-based vaccine-induced immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes quickly, based mostly on short-term studies. Here, we analyzed the kinetics and durability of the humoral responses to SARS-CoV-2 infection and vaccination using >8,000 longitudinal samples collected over a 3-year period in New York City. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state antibody titers than naive individuals. Antibody kinetics were characterized by two phases: an initial rapid decay, followed by a stabilization phase with very slow decay. Booster vaccination equalized the differences in antibody concentration between participants with and without hybrid immunity, but the peak antibody titers decreased with each successive antigen exposure. Breakthrough infections increased antibodies to similar titers as an additional vaccine dose in naive individuals. Our study provides strong evidence that SARS-CoV-2 antibody responses are long lasting, with initial waning followed by stabilization.

Age-specific transmission dynamics of SARS-CoV-2 during the first 2 years of the pandemic.

During its first 2 years, the SARS-CoV-2 pandemic manifested as multiple waves shaped by complex interactions between variants of concern, non-pharmaceutical interventions, and the immunological landscape of the population. Understanding how the age-specific epidemiology of SARS-CoV-2 has evolved throughout the pandemic is crucial for informing policy decisions. In this article, we aimed to develop an inference-based modeling approach to reconstruct the burden of true infections and hospital admissions in children, adolescents, and adults over the seven waves of four variants (wild-type, Alpha, Delta, and Omicron BA.1) during the first 2 years of the pandemic, using the Netherlands as the motivating example. We find that reported cases are a considerable underestimate and a generally poor predictor of true infection burden, especially because case reporting differs by age. The contribution of children and adolescents to total infection and hospitalization burden increased with successive variants and was largest during the Omicron BA.1 period. However, the ratio of hospitalizations to infections decreased with each subsequent variant in all age categories. Before the Delta period, almost all infections were primary infections occurring in naive individuals. During the Delta and Omicron BA.1 periods, primary infections were common in children but relatively rare in adults who experienced either reinfections or breakthrough infections. Our approach can be used to understand age-specific epidemiology through successive waves in other countries where random community surveys uncovering true SARS-CoV-2 dynamics are absent but basic surveillance and statistics data are available.

Sustained S-IgG and S-IgA antibodies to Moderna's mRNA-1273 vaccine in a Sub-Saharan African cohort suggests need for booster timing reconsiderations.

This study sought to elucidate the long-term antibody responses to the Moderna mRNA-1273 COVID-19 vaccine within a Ugandan cohort, aiming to contribute to the sparse data on m-RNA vaccine immunogenicity in Sub-Saharan Africa. We tracked the development and persistence of the elicited antibodies in 19 participants aged 18 to 67, who received two doses of the mRNA-1273 vaccine. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibodies against the spike (S) and nucleoproteins (N). The study's temporal scope extended from the baseline to one year, capturing immediate and long-term immune responses. Statistical analyses were performed using the Wilcoxon test to evaluate changes in antibody levels across predetermined intervals with the Hochberg correction for multiple comparisons. Our results showed a significant initial rise in spike-directed IgG (S-IgG) and spike-directed IgA (S-IgA) levels, which remained elevated for the duration of the study. The S-IgG concentrations peaked 14 days afterboosting, while spike-directed IgM (S-IgM) levels were transient, aligning with their early response role. Notably, post-booster antibody concentrations did not significantly change. Prior S-IgG status influenced the post-priming S-IgA dynamics, with baseline S-IgG positive individuals maintaining higher S-IgA responses, a difference that did not reach statistical difference post-boost. Three instances of breakthrough infections: two among participants who exhibited baseline seropositivity for S-IgG, and one in a participant initially seronegative for S-IgG. In conclusion, the mRNA-1273 vaccine elicited robust and persistent S-IgG and S-IgA antibody responses, particularly after the first dose, indicating potential for long-term immunity. Prior viral exposure enhances post-vaccination S-IgA responses compared to naive individuals, which aligned with the prior-naïve, post-boost. The stable antibody levels observed post-booster dose, remaining high over an extended period, with no significant secondary rise, and no difference by baseline exposure, suggest that initial vaccination may sufficiently prime the immune system for prolonged protection in this population, allowing for potential to delay booster schedules as antibody responses remained high at the time of boosting. This finding calls for a reassessment of the booster dose scheduling in this demographic.