Cross-reactive Responses Research Articles

Scrub Typhus Outbreak among Soldiers in Coastal Training Area, Australia, 2022.

A scrub typhus outbreak occurred among 24 soldiers from 2 Australian Defence Force infantry units following separate training events conducted in the same coastal location in tropical North Queensland, Australia, in June 2022. Seven soldiers visited a hospital, 5 requiring admission. Outbreak recognition was hampered by the geographic dispersion of soldiers after the exercise and delayed case identification resulting from such factors as prolonged incubation, cross-reactive serologic responses to other pathogens, the nonspecific symptoms of scrub typhus, and the illness's nonnotifiable status in the state of Queensland. Our investigation focused on personal protective measures in a subanalysis of 41 soldiers, revealing an association between scrub typhus infection and the use of doxycycline chemoprophylaxis and permethrin uniform dipping.

Component-resolved diagnostics of fruit and vegetable allergy: precise identification and individualized treatment strategies

Vegetable and fruit allergies are common types of food allergies worldwide, most of them are triggered by primary sensitization to pollen. Most allergens in vegetables and fruits belong to a few cross-reactive proteins such as PR-10 proteins, profilins, and nsLTPs. The presence of these allergens in various plants can lead to widespread cross-reactive allergic responses. Component-resolved diagnostics (CRD) can improve diagnostic accuracy by precisely identifying specific allergenic proteins, aiding physicians in making more accurate treatment and management decisions, and reducing unnecessary food avoidance. This article, based on the "Molecular Allergology User's Guide 2.0 (MAUG 2.0)" issued by the European Academy of Allergy and Clinical Immunology (EAACI), analyzes the primary mechanisms, relevant allergens, and diagnostic and clinical management strategies for vegetable and fruit allergies. By detailing and analyzing these allergenic components, this article may help the healthcare professionals to deep the understandings of vegetable and fruit allergies, offer new perspectives and practical guideline for the research and treatment of these allergies, and promot the development of precise diagnostics and personalized treatment strategies.

Mosaic and mixed HIV-1 glycoprotein nanoparticles elicit antibody responses to broadly neutralizing epitopes.

An effective human immunodeficiency virus 1 (HIV-1) vaccine will most likely have to elicit broadly neutralizing antibodies (bNAbs) to overcome the sequence diversity of the envelope glycoprotein (Env). So far, stabilized versions of Env, such as SOSIP trimers, have been able to induce neutralizing antibody (NAb) responses, but those responses are mainly strain-specific. Here we attempted to broaden NAb responses by using a multivalent vaccine and applying a number of design improvements. First, we used highly stabilized SOSIP.v9 trimers. Second, we removed any holes in the glycan shields and optimized glycan occupancy to avoid strain-specific glycan hole responses. Third, we selected five sequences from the same clade (B), as we observed previously that combining Env trimers from clade A, B and C did not improve cross-reactive responses, as they might have been too diverse. Fourth, to improve antibody (Ab) responses, the Env trimers were displayed on two-component I53-50 nanoparticles (NPs). Fifth, to favor activation of cross-reactive B cells, the five Env trimers were co-displayed on mosaic NPs. Sixth, we immunized rabbits four times with long intervals between vaccinations. These efforts led to the induction of cross-reactive B cells and cross-reactive binding Ab responses, but we only sporadically detected cross-neutralizing responses. We conclude that stabilized HIV-1 Env trimers that are not modified specifically for priming naive B cells are unable to elicit strong bNAb responses, and infer that sequential immunization regimens, most likely starting with specific germline-targeting immunogens, will be necessary to overcome Env's defenses against the induction of NAbs. The antigens described here could be excellent boosting immunogens in a sequential immunization regimen, as responses to bNAb epitopes were induced.

Signal peptide exchange alters HIV-1 envelope antigenicity and immunogenicity.

HIV-1 envelope (Env) is the key target for antibodies (Abs) against the virus and thus an important HIV-1 vaccine component. Env is synthesized from a gp160 precursor with a signal peptide (SP) at its N-terminus. This study investigated the influence of the SP on Env antigenicity and immunogenicity. Env proteins from two HIV-1 isolates, AA05 and AC02, were analyzed as gp120 and gp160 in their native wild-type (WT) forms and as chimeras with swapped SPs (AA05-02 and AC02-05). The WT and chimeric Env were assessed for antigenicity and glycosylation using monoclonal antibodies (mAbs) and glycan probes. Immunogenicity was tested in mice using three vaccine types: gp120 protein, gp120 DNA+gp120 protein, and gp120 DNA+gp160 DNA. The recombinant AC02 gp120 protein was antigenically superior to AA05 as indicated by higher reactivity with most mAbs tested. When SPs were swapped, the antigenicity of the chimeric gp120s (AA05-02 and AC02-05) resembled that of the gp120s from which the SPs were derived; AA05-02 was similar to AC02 and vice versa. Glycan probe reactivity followed a similar pattern: AA05-02 and AC02 showed similar affinity to high-mannose specific mAbs and lectins. Interestingly, the antigenicity of gp160s showed an opposite pattern; membrane-bound gp160 expressed with the AA05 SP (AA05 and AC02-05) showed greater mAb binding than gp160 with the AC02 SP (AC02 and AA05-02). Mice immunized with gp120 protein showed that AA05-02 induced stronger cross-reactive binding Ab responses than AA05 WT, and AC02 elicited stronger responses than AC02-05, indicating AC02 SP enhanced gp120 immunogenicity. However, when DNA vaccines were included (gp120 DNA+gp120 protein and gp120 DNA+gp160 DNA), the use of heterologous SPs diminished the immunogenicity of the WT immunogens. Among the three vaccine regimens tested, only gp120 DNA+gp160 DNA immunization elicited low-level Tier 2 neutralizing Abs, with AA05 WT inducing Abs with greater neutralization capabilities than AA05-02. These data demonstrate that the SP can significantly impact the antigenicity and immunogenicity of HIV-1 Env proteins. Hence, while SP swapping is a common practice in constructing Env immunogens, this study highlights the importance of careful consideration of the effects of replacing native SPs on the immunogenicity of Env vaccines.

Antibody Responses in SARS-CoV-2-Exposed and/or Vaccinated Individuals Target Conserved Epitopes from Multiple CoV-2 Antigens.

There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), short-lived immunity, and susceptibility to immune imprinting due to frequent boosting practices. In this study, we examined the specificity of cross-reactive IgG antibody responses in mRNA-vaccinated, AstraZeneca-vaccinated, and unvaccinated donors to identify potentially conserved, cross-reactive epitopes to target in order to create a broadly protective SARS-CoV-2 vaccine. Our study provides evidence for cross-reactive IgG antibodies specific to eight different spike (S) variants. Furthermore, the specificities of these cross-variant IgG antibody titers were associated to some extent with spike S1- and S2-subunit-derived epitopes P1 and P2, respectively. In addition, nucleocapsid (N)- and membrane (M)-specific IgG antibody titers correlated with N- and M-derived epitopes conserved across beta-CoVs, P3-7. This study reveals conserved epitopes of viral antigens, targeted by natural and/or vaccine-induced human immunity, for future designs of next-generation COVID-19 vaccines.

Rational selection of TbpB variants elucidates a bivalent vaccine formulation with broad spectrum coverage against Neisseria gonorrhoeae.

Neisseria gonorrhoeae is the causative agent of gonorrhea, an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. An attractive candidate vaccine antigen because of its essential function and surface exposure, the gonococcal transferrin binding protein B (TbpB) exhibits high levels of antigenic variability which poses a significant obstacle in evoking a broadly protective vaccine composition. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a potential gonococcal vaccine and identify two TbpB variants that when formulated together elicit a highly cross-reactive antibody response in both rabbits and mice against a diverse panel of TbpB variants and clinically relevant gonococcal strains. Further, this formulation performed well in experimental proxies of real-world usage, including eliciting bactericidal activity against 8 diverse gonococcal strains and decreasing the median duration of colonization after vaginal infection in female mice by two heterologous strains of N. gonorrhoeae . Together, these data support the use of a combination of TbpB variants for a broadly protective gonococcal vaccine.

M2e nanovaccines supplemented with recombinant hemagglutinin protect chickens against heterologous HPAI H5N1 challenge

Current poultry vaccines against influenza A viruses target the globular head region of the hemagglutinin (HA1), providing limited protection against antigenically divergent strains. Experimental subunit vaccines based on the conserved ectodomain of the matrix protein 2 (M2e) induce cross-reactive antibody responses, but fail to fully prevent virus shedding after low pathogenic avian influenza (LPAI) virus challenge, and are ineffective against highly pathogenic avian influenza (HPAI) viruses. This study assessed the benefits of combining nanoparticles bearing three tandem M2e repeats (NR-3M2e nanorings or NF-3M2e nanofilaments) with an HA1 subunit vaccine in protecting chickens against a heterologous HPAI H5N1 virus challenge. Chickens vaccinated with the combined formulations developed M2e and HA1-specific antibodies, were fully protected from clinical disease and mortality, and showed no histopathological lesions or virus shedding, unlike those given only HA1, NR-3M2e, or NF-3M2e. Thus, the combined vaccine formulations provided complete cross-protection against HPAI H5N1 virus, and prevented environmental virus shedding, crucial for controlling avian influenza outbreaks.

A Recombinant Mosaic HAs Influenza Vaccine Elicits Broad-Spectrum Immune Response and Protection of Influenza a Viruses.

The annual co-circulation of two influenza A subtypes, H1N1 and H3N2, viruses in humans poses significant public health threats worldwide. However, the continuous antigenic drift and shift of influenza viruses limited the effectiveness of current seasonal influenza vaccines, necessitating the development of new vaccines against both seasonal and pandemic viruses. One potential solution to this challenge is to improve inactivated vaccines by including multiple T-cell epitopes. In this study, we designed stabilized trimeric recombinant mosaic HA proteins named HAm, which contain the most potential HA T-cell epitopes of seasonal influenza A virus. We further evaluated the antigenicity, hemagglutinin activity, and structural integrity of HAm and compared its immunogenicity and efficacy to a commercial quadrivalent inactivated influenza vaccine (QIV) in mice. Our results demonstrated that the HAm vaccine was able to induce broadly cross-reactive antibodies and T-cell responses against homologous, heterologous, and heterosubtypic influenza-naive mice. Additionally, the HAm antigens outperformed QIV vaccine antigens by eliciting protective antibodies against panels of antigenically drifted influenza vaccine strains from 2009 to 2024 and protecting against ancestral viruses' lethal challenge. These results suggest that the HAm vaccine is a promising potential candidate for future universal seasonal and pandemic influenza vaccine development.

T-Cell Receptors Cross-Reactive to Coronaviral Epitopes Homologous to the SPR Peptide.

The COVID-19 pandemic caused by the rapid spread of the novel coronavirus SARS-CoV-2, has promoted an interest in studying the T-cell immune response. It was found that the polyclonal and cross-reactive T-cell response against seasonal coronaviruses and other SARS-CoV-2 strains reduced disease severity. We investigated the immunodominant T-cell epitope SPRWYFYYYL from the nucleocapsid protein of SARS-CoV-2. The immune response to this epitope is characterized by the formation of highly homologous (convergent) receptors that have been found in the T-cell receptor (TCR) repertoires of different individuals. This epitope belongs to a group of highly conserved peptides that are rarely mutated in novel SARS-CoV-2 strains and are homologous to the epitopes of seasonal coronaviruses. It has been suggested that the cross-reactive response to homologous peptides contributes to the reduction of COVID-19 severity. However, some investigators have questioned this hypothesis, suggesting that the low affinity of the cross-reactive receptors reduces the strength of the immune response. The aim of this study was to evaluate the effect of amino acid substitutions in the SPR epitope on its binding affinity to specific TCRs. For this, we performed antigen-dependent cellular expansions were performed using samples from four COVID-19-transfected donors and sequenced their TCR repertoires. The resulting SPR-specific repertoire of β-chains in TCRs had a greater sequence diversity than the repertoire of α-chains. However, the TCR repertoires of all four donors contained public receptors, three of which were cloned and used to generate the Jurkat E6-1 TPR cell line. Only one of these receptors was activated by the SPR peptide and recognized with the same affinity by its mutant homologue LPRWYFYYY from seasonal coronaviruses. This indicates that the presence of the mutation did not affect the strength of the immune response, which may explain why the cross-reactive response to the SPR epitope is so frequent and contributes positively to COVID-19 infection.

A Prototype of Graphene E-Nose for Exhaled Breath Detection and Label-Free Diagnosis of Helicobacter Pylori Infection.

Helicobacter pylori (HP), a common microanaerobic bacteria that lives in the human mouth and stomach, is reported to infect ≈50% of the global population. The current diagnostic methods for HP are either invasive, time-consuming, or harmful. Therefore, a noninvasive and label-free HP diagnostic method needs to be developed urgently. Herein, reduced graphene oxide (rGO) is composited with different metal-based materials to construct a graphene-based electronic nose (e-nose), which exhibits excellent sensitivity and cross-reactive response to several gases in exhaled breath (EB). Principal component analysis (PCA) shows that four typical types of gases in EB can be well discriminated. Additionally, the potential of the e-nose in label-free detection of HP infection is demonstrated through the measurement and analysis of EB samples. Furthermore, a prototype of an e-nose device is designed and constructed for automatic EB detection and HP diagnosis. The accuracy of the prototype machine integrated with the graphene-based e-nose can reach 92% and 91% in the training and validation sets, respectively. These results demonstrate that the highly sensitive graphene-based e-nose has great potential for the label-free diagnosis of HP and may become a novel tool for non-invasive disease screening and diagnosis.

Enhancing NA immunogenicity through novel VLP designs.

Current influenza virus vaccines poorly display key neuraminidase (NA) epitopes and do not robustly induce NA-reactive antibodies; instead, they focus on the induction of hemagglutinin (HA)-reactive antibodies. Next-generation influenza vaccines should be optimized in order to activate NA-reactive B cells and to induce a broadly cross-reactive and protective antibody response. We aimed at enhancing the immunogenicity of the NA on vaccines by two strategies: (i) modifying the HA:NA ratio of the vaccine preparation and (ii) exposing epitopes on the lateral surface or beneath the head of the NA by extending the NA stalk. The H1N1 glycoproteins from the influenza virus A/California/04/2009 strain were displayed on human immunodeficiency virus 1 (HIV-1) gag-based virus-like particles (VLP). Using the baculovirus insect cell expression system, we biased the quantity of surface glycoproteins employing two different promoters, the very late baculovirus p10 promoter and the early and late gp64 promoter. This led to a 1:1 to 2:1 HA:NA ratio, which was approximately double or triple the amount of NA as present on the wild-type influenza A virus (HA:NA ratio 3:1 to 5:1). Furthermore, by insertion of 15 amino acids from the A-New York/61/2012 strain (NY12) which prolongates the NA stalk (NA long stalk; NA-LS), we intended to improve the accessibility of the NA. Six different types of VLPs were produced and purified using a platform downstream process based on Capto-Core 700™ followed by Capto-Heparin™ affinity chromatography combined with ultracentrifugation. These VLPs were then tested in a mouse model. Robust titers of antibodies that inhibit the neuraminidase activity were elicited even after vaccination with two low doses (0.3 μg) of the H1N1 VLPs without compromising the anti-HA responses. In conclusion, our results demonstrate the feasibility of the two developed strategies to retain HA immunogenicity and improve NA immunogenicity as a future influenza vaccine candidate.

Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals

Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated the effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding the greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate mapping, in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced by mosaic-8b, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19-vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.

Site-specific serology unveils cross-reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes.

Efficient identification of human monoclonal antibodies targeting specific antigenic sites is pivotal for advancing vaccines and immunotherapies against infectious diseases and cancer. Existing screening techniques, however, limit our ability to discover monoclonal antibodies with desired specificity. In this study, we introduce a novel method, blocking of binding (BoB) enzyme-linked immunoassay (ELISA), enabling the detection of high-avidity human antibodies directed to defined epitopes. Leveraging BoB-ELISA, we analyzed the antibody response to known epitopes of influenza A hemagglutinin (HA) in the serum of vaccinated donors. Our findings revealed that serum antibodies targeting head epitopes were immunodominant, whereas antibodies against the stem epitope, although subdominant, were highly prevalent. Extending our analysis across multiple HA strains, we examined the cross-reactive antibody response targeting the stem epitope. Importantly, employing BoB-ELISA we identified donors harboring potent heterosubtypic antibodies targeting the HA stem. B-cell clonal analysis of these donors revealed three novel, genealogically independent monoclonal antibodies with broad cross-reactivity to multiple HAs. In summary, we demonstrated that BoB-ELISA is a sensitive technique for measuring B-cell epitope immunogenicity, enabling the identification of novel monoclonal antibodies with implications for enhanced vaccine development and immunotherapies.

Acetylated bacterial proteins as potent antigens inducing an anti-modified protein antibody response

ObjectiveGut-residing bacteria, such as Escherichia coli, can acetylate their proteome under conditions of amine starvation. It is postulated that the (gut) microbiome is involved in the breach of immune tolerance...

Effects of genetic diversity on the allergenicity of peanut (Arachis hypogaea) proteins: identification of the hypoallergenic accessions using BALB/c mice model and in silico analysis of Ara h 3 allergen cross-reactivity

This study investigated the effects of genetic diversity in the allergenicity of peanut and assessed the allergenic capacity of six Arachis hypogaea accessions using a Balb/c mouse model. It also explored potential cross-reactivities between Ara h 3 (peanut allergen) and Gly m (soybean allergen) using computational tools. Female Balb/c mice were injected with peanut protein extracts and alum. Serum-specific antibodies (IgE, IgGt, IgG1, IgG2a) were measured using ELISA, and allergic protein profiles were examined via western blot. Structural homology, B cell epitopes, and molecular interactions between Ara h 3 and Gly m with human IgE were also investigated. The mice developed high sIgE and sIgG1 responses, with antibodies recognizing 19 bands on western blot. Notably, Saharan accessions showed unique features such as no bands on western blot profiles, reduced anaphylactic symptoms, lower IgE titers, and less intestinal tissue damage. Molecular docking results suggest significant cross-allergenicity, supported by allergenicity predictions and structural homology analysis. This comprehensive analysis provides insights into shared epitopes, potential competition for binding sites, and molecular dynamics of cross-reactive responses, enhancing understanding of food allergen interactions. The study recommends using Algerian Sahara peanut accessions in breeding, genomics studies, and industry for safer peanut options for individuals with allergies. SignificanceThe significance of this study lies in its contribution to addressing a major public health issue: peanut allergy, which represents a significant cause of anaphylaxis affecting numerous individuals and families worldwide. By exploring the genetic diversity of peanut proteins and identifying hypoallergenic accessions through experimental and computational approaches, this research offers valuable insights for mitigating allergic reactions. The findings highlight that certain accessions from the Saharan region exhibit reduced allergenicity, resulting in attenuated anaphylactic symptoms, lower IgE levels, and reduced intestinal damage in murine models. Furthermore, the study's in silico analysis sheds light on the issue of cross-reactivity between peanut and soybean allergens, providing crucial information for understanding allergen interactions at the molecular level. Overall, this research contributes to advancing knowledge in the field of food allergen research and has practical implications for improving the quality of life for individuals allergic to peanuts, particularly through the selection of safer peanut varieties and their cultivation.

Neutralizing antibody responses against contemporary and future influenza A(H3N2) viruses in paradoxical clades elicited by repeated and single vaccinations.

As one of the most effective measures to prevent seasonal influenza viruses, annual influenza vaccination is globally recommended. Nevertheless, evidence regarding the impact of repeated vaccination to contemporary and future influenza has been inconclusive. A total of 100 subjects singly or repeatedly immunized with influenza vaccines including 3C.2a1 or 3C.3a1 A(H3N2) during 2018-2019 and 2019-2020 influenza season were recruited. We investigated neutralization antibody by microneutralization assay using four antigenically distinct A(H3N2) viruses circulating from 2018 to 2023, and tracked the dynamics of B cell receptor (BCR) repertoire for consecutive vaccinations. We found that vaccination elicited cross-reactive antibody responses against future emerging strains. Broader neutralizing antibodies to A(H3N2) viruses and more diverse BCR repertoires were observed in the repeated vaccination. Meanwhile, a higher frequency of BCR sequences shared among the repeated-vaccinated individuals with consistently boosting antibody response was found than those with a reduced antibody response. Our findings suggest that repeated seasonal vaccination could broaden the breadth of antibody responses, which may improve vaccine protection against future emerging viruses.

Assessing the Correlation of Periodontal Inflamed Surface Area (PISA) With Systemic Inflammatory Markers.

Background Periodontitis has a vital role in eliciting a cross-reactivity or systemic inflammatory response, making periodontal inflamed surface area (PISA)a primary contributor to the inflammatory burden posed by periodontitis. PISA helps in the quantification of the amount of inflamed periodontal tissue. However, the existing literature data concerning PISA as an indicator of inflammatory burden are scarce, with limited research on the relationship between systemic inflammatory markers and PISA. Aim The present clinic-hematological cross-sectional study aimed to correlate PISA with systemic inflammatory markers. The studyalso aimed to assess serum concentrations of inflammatory markers such as erythrocyte sedimentation rates (ESR), C-reactive protein (CRP), and peripheral blood markers such as neutrophils and monocytes and to correlate these markers with PISA. Methods The study assessed 62 subjects, who were divided into two groups of 31 subjects, each followingbleeding on probing (BOP) criteria. Group I consisted of subjects with generalized chronic gingivitis, and Group II included subjects with generalized chronic periodontitis. In two groups, BOP, probing pocket depth, clinical attachment level, and gingival recession were assessed along with PISA by a custom-made R function derived from a pre-existing, freely available MS Excel spreadsheet(Microsoft Corporation, Redmond, Washington). The results of the assessment were then compared. Results A statistically highly significant positive correlation was seen in PISA and CRP with a correlation coefficient of 0.4875 and p-value of 0.000059. A similar statistically significant positive correlation was seen in ESR and PISA with a correlation coefficient of 0.4089 and p-value of 0.000968. A statistically non-significant correlation was seen in neutrophils and PISA with p=0.576018. However, a moderate and positive statistically significant association was seen in monocyte and PISA with a correlation coefficient of 0.3258 and p-value of 0.009956. Conclusions The present study concludes that most of the common systemic inflammatory markers have a positive correlation with PISA. However, more studies are required to establish this correlation.

Accelerated and precise identification of antioxidants and pesticides using a smartphone-based colorimetric sensor array

The integration of smartphones with conventional analytical approaches plays a crucial role in enhancing on-site detection platforms for point-of-care testing. Here, we developed a simple, rapid, and efficient three-channel colorimetric sensor array, leveraging the peroxidase (POD)-like activity of polydopamine-decorated FeNi foam (PDFeNi foam), to identify antioxidants using both microplate readers and smartphones for signal readouts. The exceptional catalytic capacity of PDFeNi foam enabled the quick catalytic oxidation of three typical peroxidase substrates (TMB, OPD and 4-AT) within 3 min. Consequently, we constructed a colorimetric sensor array with cross-reactive responses, which was successfully applied to differentiate five antioxidants (i.e., glycine (GLY), glutathione (GSH), citric acid (CA), ascorbic acid (AA), and tannic acid (TAN)) within the concentration range of 0.1–10 μM, quantitatively analyze individual antioxidants (with AA and CA as model analytes), and assess binary mixtures of AA and GSH. The practical application was further validated by discriminating antioxidants in serum samples with a smartphone for signal readout. In addition, since pesticides could be absorbed on the surface of PDFeNi foam through π-π stacking and hydrogen bonding, the active sites were differentially masked, leading to featured modulation on POD-like activity of PDFeNi foam, thereby forming the basis for pesticides discrimination on the sensor array. The nanozyme-based sensor array provides a simple, rapid, visual and high-throughput strategy for precise identification of various analytes with a versatile platform, highlighting its potential application in point-care-of diagnostic, food safety and environmental surveillance.

Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals.

Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced by mosaic-8b, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.

Informing the Need for a SARS-CoV-2 Booster Based on the Immune Responses Among Young Healthy Adults to Variants Circulating in Late 2023.

COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity. In this cross-sectional study, we evaluated the adaptive immune responses in US active duty personnel who completed a COVID-19 primary vaccine series and had heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were based on the most recent exposure in terms of timing (within or beyond 12 months) and type (vaccine or infection). Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants when compared with previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was >12 months from enrollment. In contrast, the CD4+ T-cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing.