Search Results (3,230)

Breast milk can provide passive immunity to infants, serving as a valuable source of maternal antibodies while remaining a non-invasive sample for investigating maternal immune responses. To date, no studies have evaluated SARS-CoV-2 and potentially cross-reactive HCoV antibodies in breast milk following bamlanivimab administration. A 36-year-old postpartum female was PCR-positive for SARS-CoV-2 four days post-delivery. Bamlanivimab was administered intravenously two days later. Breast milk was collected before bamlanivimab infusion, daily for two weeks post-infusion, then weekly until 102 days post-infusion. Mother and infant sera were collected only at 102 days post-infusion. All milk and serum samples were tested for IgG antibodies against SARS-CoV-2 and HCoV. We observed two distinct SARS-CoV-2 antibody peaks at days 3 and 29 post-infusion, likely representing bamlanivimab transfer and the post-infection antibody response. Beta-HCoV antibodies showed two peaks at days 6 and 29, potentially representing backboosted beta-HCoV responses and/or antibody cross-reactivity with SARS-CoV-2. Infant seropositivity for SARS-CoV-2 102 days post-infusion may represent antibodies from passive transfer via breastfeeding or a subclinical infection. This case highlights the value of breast milk as a non-invasive and repeatable sample to help understand maternal immune responses post-infection, exogenous antibody infusion, and passive antibody transfer during breastfeeding, which can provide insights into maternal–infant health research. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Background: This study aimed to assess the prevalence of SARS-CoV-2 infection, vaccination, and immune status among a population, both Dentists and University Professors, within a clinical setting at one and at 12 months after COVID-19 vaccination. Methods: A cross-sectional study involving 47 professionals (aged 27–52) was conducted in the University Fernando Pessoa. Participants completed an online survey on SARS-CoV-2 infection status and vaccination, received and provided plasma samples for serological analysis. The protocol was approved by the UFP-Ethics Committee. Anti-S1-RBD SARS-CoV-2 IgM and IgG antibody titration values (AU/mL) were measured, by enzyme-linked-immunosorbent assay (ELISA), with reactive immunoglobulins (Ig) seropositivity for values ≥1 AU/mL. Results: SARS-CoV-2 infection rate increased from 8.5% in July 2021 to 48.9% in June 2022, with 8.5% experiencing reinfection. Vaccination rate was 91.5% by July 2021 and increased slightly to 93.6% by June 2022; 72.3% of the sample received a third dose. IgG seropositivity increased from 91.5% to 95.7% in June 2022. After one-year, significant associations were found between IgG seropositivity and both participant’s age (p = 0.009; <50 years) and vaccine doses (p = 0.003; 1–3 doses) received. Conclusions: SARS-CoV-2 infection rate, vaccination, and IgG seropositivity rates were high and increased over one year. The age and vaccination status were associated with the immunity status at 12th month follow-up. Findings highlight variability in IgG seroprevalence due to multiple influencing factors, which justifies future studies. Full article

Background: Understanding the duration and quality of immune memory following SARS-CoV-2 infection and vaccination is critical for informing public health strategies and vaccine development. While waning antibody levels have raised concerns about long-term protection, the persistence of memory B cells (MBCs) and T cells plays a vital role in sustaining immunity. Materials and Methods: We conducted a longitudinal prospective study over 12 months, enrolling 285 participants in total, either after natural infection or vaccination with BNT162b2 or mRNA-1273. Peripheral blood samples were collected at four defined time points (baseline, 1–2 months, 6–7 months, and 12–13 months after vaccination or disease onset). Immune responses were assessed through serological assays quantifying anti-RBD IgG and neutralizing antibodies, B-ELISPOT, and multiparameter flow cytometry for S1-specific memory B cells. Results: Both mRNA vaccines induced robust B cell and antibody responses, exceeding those observed after natural infection. Memory B cell frequencies peaked at 6 months and declined by 12 months, but remained above the baseline. The mRNA-1273 vaccine elicited stronger and more durable humoral and memory B-cell-mediated immunity compared to BNT162b2, likely influenced by its higher mRNA dose and longer prime-boost interval. Class-switched memory B cells and S1-specific B cells were significantly expanded in vaccine recipients. Natural infection induced more heterogeneous immune memory. Conclusions: Both mRNA vaccination and natural SARS-CoV-2 infection induce a comparable expansion of memory B cell subsets, reflecting a consistent pattern of humoral immune responses across all studied groups. These findings highlight the importance of vaccination in generating sustained immunological memory and suggest that the vaccine platform and dosage influence the magnitude and durability of immune responses against SARS-CoV-2. Full article

Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. Methods: Specifically, four proprietary adjuvants (EmT4^TM, LiT4Q^TM, MiT4^TM, and AlT4^TM) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. Results: Results showed significant improvement in immune response strength and breadth—especially against more distant SARS-CoV-2 variants such as Omicron—when adjuvants were used in combination with boosters following an RNA vaccine prime. Conclusions: The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity. Full article

Background/Objectives: An initial COVID-19 candidate vaccine containing a purified ancestral SARS-CoV-2 spike antigen was characterized with an ELISA using recombinant monoclonal antibodies (mAbs) generated against this variant. Upon the emergence of a new Beta (B.1.351) spike variant early in the pandemic, the assessment of a bivalent vaccine containing ancestral and Beta spike antigens began. Due to accelerated project timelines, mAbs generated specifically against the Beta spike antigen were not available at the time to address assay development and vaccine testing requirements. Methods: Using only the initial mAb panel raised against the ancestral spike antigen, an epitope-blocking ELISA strategy was developed to independently measure Beta spike antigen in bivalent vaccine formulations. To facilitate this, epitope profiling of spike antigens from both ancestral and Beta variants was performed with biolayer interferometry and hydrogen–deuterium exchange mass spectrometry using the original panel of mAbs. Results: The resulting blocking ELISA was precise and specific for the Beta spike antigen and detected the expected amount of this antigen in bivalent vaccine formulations. The specific amount of ancestral spike protein in the bivalent vaccine was also confirmed using the original ELISA developed at the onset of the pandemic. Conclusions: This epitope-blocking strategy helped to overcome key reagent availability issues and could be applied to other projects involving related proteins. Full article

Background: Vaccination effectively reduces the risk of infection, including COVID-19 yet older adults often receive insufficient attention despite their increased vulnerability. The study aimed to correlate serological results with underlying conditions, vaccination status, and COVID-19 history. Methods: This non-interventional, multicenter study aimed to assess vaccination coverage and SARS-CoV-2 antibody levels among residents of eight long-term care facilities (LTCFs) in Southern Poland. Data collection took place between January and June 2022, with 429 participants recruited based on their ability to provide informed consent and their residency in LTCFs. Sociodemographic data, medical history, and COVID-19-related information—including infection history and vaccination status—were collected through surveys. Blood samples were obtained for serological testing using enzyme-linked immunosorbent assays (ELISA) to detect anti-SARS-CoV-2 antibodies. Statistical analysis, including Spearman’s correlation, revealed significant associations between antibody levels and vaccination status, as well as between RT-PCR-confirmed COVID-19 infections and higher antibody titers. Results: Among the seven different qualitative serological, only the Anti-SARS-CoV-2 NCP (IgG) and Anti-SARS-CoV-2 (IgA) tests showed a positive correlation with the Anti-SARS-CoV-2 QuantiVac (IgG) test, which was used as a comparator. A weak correlation was noted with the age of the residents. Conclusions: Our findings suggest that vaccination positively influences antibody responses, underscoring the importance of immunization among LTCF residents. Additionally, certain comorbidities—such as degenerative joint disease and diabetes—showed weak correlations with higher antibody levels. This study provides valuable insights into the humoral immune response to COVID-19 in vulnerable populations residing in LTCFs. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants. Full article

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope footprint and distributed hotspot architecture, additionally supported by backbone-mediated specific interactions, which are less sensitive to amino acid substitutions and together enable exceptional tolerance to mutational escape. In contrast, BD-604 and OMI-42 exhibit localized binding modes with strong dependence on side-chain interactions, rendering them particularly vulnerable to escape mutations at K417N, L455M, F456L and A475V. Similarly, P5S-1H1 and P5S-2B10 display intermediate behavior—effective in some contexts but increasingly susceptible to antigenic drift due to narrower epitope coverage and concentrated hotspots. Our computational predictions show strong agreement with experimental deep mutational scanning data, validating the accuracy of the models and reinforcing the value of binding hotspot mapping in predicting antibody vulnerability. This work highlights that neutralization breadth and durability are not solely dictated by epitope location, but also by how binding energy is distributed across the interface. The results provide atomistic insight into mechanisms driving resilience to immune escape for broadly neutralizing antibodies targeting the ACE2 binding interface—which stems from cumulative effects of structural diversity in binding contacts, redundancy in interaction patterns and reduced vulnerability to mutation-prone positions. Full article

Background: Immunological strategies for antibody-guided vaccine design intend to enhance viral neutralization and protection and increase efficacy. Here, we discuss advances in antibody-guided vaccine design and current antibody-guided strategies, including epitope-based, nanoparticle-based, and scaffold-based vaccine approaches. We review the challenges and limitations of vaccines against different pathogens, such as influenza A virus, HIV-1 virus, single-celled malaria parasite, respiratory syncytial virus, and SARS-CoV-2. We summarize the available literature guidance, including emerging techniques in immunological vaccine design, to help understand and improve antibody-based immunity. The search strategy we applied is a comprehensive literature review of major databases, with specific search terms related to antibody-mediated vaccine design, viral neutralization, and immune protection. We discuss the how future directions for next-generation vaccine platforms and personalized vaccines based on immunogenetics will help improve vaccine design for increased specificity and potency of antibodies that neutralize pathogens, offering more precise and effective immune responses and, therefore, protection. Full article

Background/Objectives: SARS-CoV-2 vaccine candidates comprising the receptor binding domain (RBD) of the spike protein have been shown to confer protection against infection. Previous research evaluating vaccine candidates with SARS-CoV-2 RBD fused to ferritin (RBD-ferritin) and other scaffolds suggested that multimeric assemblies of RBD can enhance antigen presentation to improve the potency and breadth of immune responses. Though RBDs directly fused to a self-assembling scaffold can be delivered as messenger RNA (mRNA) formulated with lipid nanoparticles (LNPs), reports of SARS-CoV-2 vaccine candidates that combine these approaches remain scarce. Methods: Here, we designed RBD fused to AP205 or TIP60 self-assembling nanoparticles following a search of available structures focused on several scaffold properties. RBD-AP205 and RBD-TIP60 were tested for antigenicity following transfection and for immunogenicity and neutralization potency when delivered as mRNA in mice, with RBD-ferritin as a direct comparator. Results: All scaffolded RBD constructs were readily secreted to transfection supernatant and showed antigenicity in ELISA, though clear heterogeneity in assembly was observed. RBD-AP205 and RBD-TIP60 also exhibited robust antibody binding and neutralization titers in mice that were comparable to those elicited by RBD-ferritin or a full-length membrane-bound spike. Conclusions: These data suggest that AP205 and TIP60 can present RBD as effectively as ferritin and induce similar immune responses. By describing additional scaffolds for multimeric display that accommodate mRNA delivery platforms, this work can provide new tools for future vaccine design efforts. Full article

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

Ferritin nanocages with spherical shells carry proteins or antigens that enable their use as highly efficient nanoreactors and nanocarriers. Mimicking the surface Spike (S) receptor-binding domain (RBD) from SARS-CoV-2, ferritin nanocages induce neutralizing antibody production or block viral entry. Herein, by implementing molecular dynamics simulation, we evaluate the efficiency in the interaction pattern (active or alternative sites) of H-ferritin displaying the 24 S RBDs with host-cell-receptor or monoclonal antibodies (mAbs; B38 or VVH-72). Our constructed nanocage targeted the receptor- or antibody-binding interfaces, suggesting that mAbs demonstrate an enhanced binding affinity with the RBD, with key interactions originating from its variable heavy chain. The S RBD interactions with ACE2 and B38 involved the same binding site but led to divergent dynamic responses. In particular, both B38 chains showed that asymmetric fluctuations had a major effect on their engagement with the Spike RBD. Although the receptor increased the binding affinity of VVH-72 for the RBD, the mAb structural orientation on the nanocage remained identical to its conformation when bound to the host receptor. Overall, our findings characterize the essential pharmacophore formed by Spike RBD residues over nanocage molecules, which mediates high-affinity interactions with either binding partner. Importantly, the ferritin-displayed RBD maintained native receptor and antibody binding profiles, positioning it as a promising scaffold for pre-fusion stabilization and protective RBD vaccine design. Full article

Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELD^TM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: Healthy adults over 18 years of age received two injections of ECV-19 or CS vaccines, with 4 weeks between prime and boost. Analysis was carried out in individuals with immunogenicity measurements available at all 4 timepoints (weeks 0, 6, 30, and 56; n = 535 for ECV-19 and n = 260 for CS). Results: 2 weeks after boosting (week 6), ECV-19 elicited higher median anti-RBD IgG (1512 vs. 340 BAU/mL, p < 0.001) and neutralizing antibodies (1280 vs. 453 median microneutralization (MN) titer, p < 0.001) compared to CS. Anti-RBD IgG remained higher for ECV-19 compared to CS through week 30 (412 vs. 238 BAU/mL, p < 0.001) and 56 (425 vs. 260 BAU/mL, p < 0.001). MN titers remained higher for ECV-19 compared to CS through week 30 (640 vs. 453, p < 0.001) and 56 (453 vs. 320, p < 0.001). Correlation between anti-RBD IgG and neutralization titers persisted throughout the study. Women generally exhibited greater antibody responses than men. In the first six months following immunization, the ECV-19 group had a median antibody half-life of 80 days for anti-RBD IgG and 112 days for MN titer. In the subsequent six months, antibody half-life increased to 237 days for anti-RBD IgG and 168 days for MN titer. Conclusions: Following initial prime-boost vaccination, ECV-19 maintained higher anti-RBD IgG and neutralizing antibody titers relative to the CS comparator over a full-year period. Full article