Development of a Liposome-Based Serological Assay for SARS-CoV-2 Variants with Special Emphasis on Coupling Chemistries Required to Maintain Protein Antigenicity.

The conjugation of proteins to the outer membranes of liposomes is a standard procedure used in bioanalytical and drug delivery approaches. Herein, we describe the development of a liposome-based surrogate assay for the quantification of SARS-CoV-2 neutralizing antibodies. Taking into consideration differences in amino acid sequences within the receptor-binding domain (RBD) of SARS-CoV-2 Spike proteins derived from five selected variants of concern (VoC), we studied the impact of coupling chemistries on physicochemical properties and antigenicity.

Exposure to two antigenically distinct SARS-CoV-2 variants broadens neutralization patterns.

Previous exposure to one severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant influences neutralizing antibody responses induced by subsequent exposures. Consecutive exposures predominantly back-boost pre-existing immunity and expand cross-neutralizing antibodies while de novo variant-specific responses are poorly induced. In this study, we analyzed neutralizing antibodies against a panel of variants in plasma samples from individuals after exactly two exposures: twice pre-Omicron variant (either two dose vaccinated or infected and one dose vaccinated), pre-Omicron followed by early Omicron variant, or twice early Omicron variant.

Consensus Sequences for and Introduced into HIV-1 Clade B Laboratory Strains Differentially Influence the Impact of Point Mutations Associated with Immune Escape and with Drug Resistance on Viral Replicative Capacity.

Viral evasion from effective human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses and from antiretroviral therapy through viral sequence variation is frequently accompanied by a loss in viral fitness. The impact of sequence variations on replication capacity in vitro was mostly studied by introducing single mutations into a specific clonal strain such as NL4-3. How the specific viral backbone itself impacts replicative fitness remains elusive.

Dynamics of Dental Education, Organization, and Regulation of Dental Practice in Europe 2016-2023.

Background: This study examines shifts in dental education, organization of dentists, changes in regulation of dental practice across European countries and comparing differences between 2016 and 2023 of member states of the FDI World Dental Federation and WHO-Europe region.

Methods: Surveys conducted by the ERO-FDI in 2016 and 2023 included 45 countries (34 ERO and 11 non-members). Data on practice types, legal frameworks, education, and organization were collected via national dental associations.

Genome-wide association study of long COVID.

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear.

Enhanced variant neutralization through glycan masking of SARS-CoV-2 XBB1.5 RBD.

SARS-CoV-2 continues to evolve antigenically under the immune pressure exerted by both natural infection and vaccination. As new variants emerge, we face the recurring challenge of updating vaccines at significant financial cost to maintain their efficacy. To address this, novel strategies are needed to enhance the breadth of protection offered by vaccines or, at a minimum, extend their effectiveness over time.

In danger: HIV vaccine research and development in Europe.

Highly effective antiretroviral-based HIV prevention plays an important role in ending the global HIV/AIDS epidemic. However, the sustainable control of the epidemic is hampered by unequal access to prevention options, including HIV testing, alongside with drug resistance and ongoing barriers to accessing sustainable HIV treatment. Therefore, an HIV vaccine, combined with effective prevention and treatment, remains an absolute necessity to control the epidemic.

Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses.

Background: The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study.

Methods: 173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.

Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants.

Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed.

Changing dental profession in the WHO European region: analysis of the organization and education framework.

Objectives: The study examines the impact of changes on dental education and practice in Europe, including the development of new practice models such as investor-owned dental centers and practice chains.

Method And Materials: This study aimed to collect and critically examine data regarding the care environment, education, and organizational structures of the dental profession across European Regional Organization of the FDI World Dental Federation (ERO) member states and other countries in the World Health Organization European region. A questionnaire from the ERO was used.

Evolution of protective SARS-CoV-2-specific B and T cell responses upon vaccination and Omicron breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron breakthrough infection (BTI) induced better protection than triple vaccination. To address the underlying immunological mechanisms, we studied antibody and T cell response dynamics during vaccination and after BTI. Each vaccination significantly increased peak neutralization titers with simultaneous increases in circulating spike-specific T cell frequencies.

Hybrid immunity by two COVID-19 mRNA vaccinations and one breakthrough infection provides a robust and balanced cellular immune response as basic immunity against severe acute respiratory syndrome coronavirus 2.

This longitudinal prospective controlled multicenter study aimed to monitor immunity generated by three exposures caused by breakthrough infections (BTI) after COVID-19-vaccination considering pre-existing cell-mediated immunity to common-corona-viruses (CoV) which may impact cellular reactivity against SARS-CoV-2. Anti-SARS-CoV-2-spike-IgG antibodies (anti-S-IgG) and cellular reactivity against Spike-(S)- and nucleocapsid-(N)-proteins were determined in fully-vaccinated (F) individuals who either experienced BTI (F+BTI) or had booster vaccination (F+Booster) compared to partially vaccinated (P+BTI) and unvaccinated (U) from 1 to 24 weeks post PCR-confirmed infection. High avidity anti-S-IgG were found in F+BTI compared to U, the latter exhibiting increased long-lasting pro-inflammatory cytokines to S-stimulation.

Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract.

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa.

A Multi-Faceted Binding Assessment of Aptamers Targeting the SARS-CoV-2 Spike Protein.

The COVID-19 pandemic has underscored the critical need for the advancement of diagnostic and therapeutic platforms. These platforms rely on the rapid development of molecular binders that should facilitate surveillance and swift intervention against viral infections. In this study, we have evaluated by three independent research groups the binding characteristics of various published RNA and DNA aptamers targeting the spike protein of the SARS-CoV-2 virus.

Prolonged delivery of HIV-1 vaccine nanoparticles from hydrogels.

Immunization is a straightforward concept but remains for some pathogens like HIV-1 a challenge. Thus, new approaches towards increasing the efficacy of vaccines are required to turn the tide. There is increasing evidence that antigen exposure over several days to weeks induces a much stronger and more sustained immune response compared to traditional bolus injection, which usually leads to antigen elimination from the body within a couple of days.

Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells.

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32 nanoprotrusions deposit distinct plasma membrane patches onto target T cells.

Transgene expression knock-down in recombinant Modified Vaccinia virus Ankara vectors improves genetic stability and sustained transgene maintenance across multiple passages.

Modified vaccinia virus Ankara is a versatile vaccine vector, well suited for transgene delivery, with an excellent safety profile. However, certain transgenes render recombinant MVA (rMVA) genetically unstable, leading to the accumulation of mutated rMVA with impaired transgene expression. This represents a major challenge for upscaling and manufacturing of rMVA vaccines.

Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors' PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen.

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients.

Population-based study of the durability of humoral immunity after SARS-CoV-2 infection.

SARS-CoV-2 antibody quantity and quality are key markers of humoral immunity. However, there is substantial uncertainty about their durability. We investigated levels and temporal change of SARS-CoV-2 antibody quantity and quality.

A shift of paradigm: From avoiding nanoparticular complement activation in the field of nanomedicines to its exploitation in the context of vaccine development.

The complement system plays a central role in our innate immunity to fight pathogenic microorganisms, foreign and altered cells, or any modified molecule. Consequences of complement activation include cell lysis, release of histamines, and opsonization of foreign structures in preparation for phagocytosis. Because nanoparticles interact with the immune system in various ways and can massively activate the complement system due to their virus-mimetic size and foreign texture, detrimental side effects have been described after administration like pro-inflammatory responses, inflammation, mild to severe anaphylactic crisis and potentially complement activated-related pseudoallergy (CARPA).

Assessing immunogenicity barriers of the HIV-1 envelope trimer.

Understanding the balance between epitope shielding and accessibility on HIV-1 envelope (Env) trimers is essential to guide immunogen selection for broadly neutralizing antibody (bnAb) based vaccines. To investigate the antigenic space of Env immunogens, we created a strategy based on synthetic, high diversity, Designed Ankyrin Repeat Protein (DARPin) libraries. We show that DARPin Antigenicity Analysis (DANA), a purely in vitro screening tool, has the capability to extrapolate relevant information of antigenic properties of Env immunogens.

Immunogenicity of a silica nanoparticle-based SARS-CoV-2 vaccine in mice.

Safe and effective vaccines have been regarded early on as critical in combating the COVID-19 pandemic. Among the deployed vaccine platforms, subunit vaccines have a particularly good safety profile but may suffer from a lower immunogenicity compared to mRNA based or viral vector vaccines. In fact, this phenomenon has also been observed for SARS-CoV-2 subunit vaccines comprising the receptor-binding domain (RBD) of the spike (S) protein.