Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa: A randomized crossover phase 2a/2b trial.

COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo.

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial.

Background: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2.

Release dynamics of nanodiamonds created by laser-driven shock-compression of polyethylene terephthalate.

Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states.

Effect of Starch and Paperboard Reinforcing Structures on Insulative Fiber Foam Composites.

Single-use plastic foams are used extensively as interior packaging to insulate and protect items during shipment but have come under increasing scrutiny due to the volume sent to landfills and their negative impact on the environment. Insulative compression molded cellulose fiber foams could be a viable alternative, but they do not have the mechanical strength of plastic foams. To address this issue, a novel approach was used that combined the insulative properties of cellulose fiber foams, a binder (starch), and three different reinforcing paperboard elements (angular, cylindrical, and grid) to make low-density foam composites with excellent mechanical strength.

A Pseudovirus-Based Neutralization Assay for SARS-CoV-2 Variants: A Rapid, Cost-Effective, BSL-2-Based High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation.

Neutralizing antibody responses from COVID-19 vaccines are pivotal in conferring protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Effective COVID-19 vaccines and assays measuring neutralizing antibodies against emerging variants (i.e.

Immunogenicity and safety of a bivalent (omicron BA.5 plus ancestral) SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose: interim analysis of a phase 3, non-inferiority, randomised, clinical trial.

Background: SARS-CoV-2 variants evade immunity despite vaccination with prototype COVID-19 vaccines or previous infection. The 2019nCoV-311 (part 2) study is evaluating immune responses after two booster doses of a vaccine containing the omicron BA.5 subvariant spike protein in adults previously vaccinated with a prototype mRNA vaccine.

Optically-Trapped Nanodiamond-Relaxometry Detection of Nanomolar Paramagnetic Spins in Aqueous Environments.

Probing electrical and magnetic properties in aqueous environments remains a frontier challenge in nanoscale sensing. Our inability to do so with quantitative accuracy imposes severe limitations, for example, on our understanding of the ionic environments in a diverse array of systems, ranging from novel materials to the living cell. The Nitrogen-Vacancy (NV) center in fluorescent nanodiamonds (FNDs) has emerged as a good candidate to sense temperature, pH, and the concentration of paramagnetic species at the nanoscale, but comes with several hurdles such as particle-to-particle variation which render calibrated measurements difficult, and the challenge to tightly confine and precisely position sensors in aqueous environment.

Three immunizations with Novavax's protein vaccines increase antibody breadth and provide durable protection from SARS-CoV-2.

The immune responses to Novavax's licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-M adjuvanted vaccines predominantly elicits immune events in local tissues with little spillover to the periphery. A third dose of an updated vaccine based on the Gamma (P.

Articulating Hip Spacers with a Constrained Acetabular Liner: Effect of Acetabular Bone Loss and Cementation Quality.

Articulating hip spacers for periprosthetic joint infection (PJI) offer numerous advantages over static spacers such as improved patient mobilization, hip functionality, and soft tissue tension. Our study aimed to determine complication rates of a functional articulating spacer using a constrained liner to determine the role of acetabular cementation mantle and bone loss on the need for second-stage surgery. A retrospective review of 103 patients was performed and demographic information, spacer components and longevity, spacer-related complications, reinfection rates, and grade of bone loss and acetabular cement mantle quality were determined.

Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial.

Importance: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown.

Objective: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo.

Design, Setting, And Participants: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022.

A Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Immunoglobulin G Assay: A Robust Method for Evaluation of Vaccine Immunogenicity Using an Established Correlate of Protection.

As the COVID-19 pandemic continues, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge. Immunogenicity evaluation of vaccines and identification of correlates of protection for vaccine effectiveness is critical to aid the development of vaccines against emerging variants. Anti-recombinant spike (rS) protein immunoglobulin G (IgG) quantitation in the systemic circulation (serum/plasma) is shown to correlate with vaccine efficacy.

Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has significantly reduced the efficacy of some approved vaccines. A fourth dose of NVX-CoV2373 (5 µg SARS-CoV-2 recombinant spike [rS] protein + 50 µg Matrix-M™ adjuvant; Novavax, Gaithersburg, MD) was evaluated to determine induction of cross-reactive antibodies to variants of concern. A phase II randomized study (NCT04368988) recruited participants in Australia and the United States to assess a primary series of NVX-CoV2373 followed by two booster doses (third and fourth doses at 6-month intervals) in adults 18-84 years of age.

Safety, efficacy, and immunogenicity of the NVX-CoV2373 vaccine.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. As SARS-CoV-2 moves into endemic status, vaccination remains a key element in protecting the health of individuals, societies, and economies worldwide.

Areas Covered: NVX-CoV2373 (Novavax, Gaithersburg, MD) is a recombinant protein vaccine composed of SARS-CoV-2 spike trimer nanoparticles formulated with saponin-based Matrix-M™ adjuvant (Novavax, Gaithersburg, MD).

Immunogenicity of NVX-CoV2373 in PREVENT-19: A Phase 3, Randomized, Placebo-Controlled Trial in Adults in the United States and Mexico.

Background: NVX-CoV2373, an adjuvanted, recombinant SARS-CoV-2 spike (rS) protein vaccine, consistently demonstrated protective efficacy against COVID-19 in clinical trials and has received regulatory authorizations or approvals worldwide.

Methods: PREVENT-19 (NCT04611802) is a phase 3, randomized, observer-blinded, placebo-controlled trial evaluating safety, immunogenicity, and efficacy of NVX-CoV2373 in ≈30 000 participants ≥18 years in the United States and Mexico. Vaccine humoral immune response (ie, serum immunoglobulin [IgG] antibodies, hACE2 receptor binding inhibition antibodies, and neutralizing antibodies to SARS-CoV-2) (ancestral strain) was assessed in 1200 participants randomly selected and equally divided between participants 18-64 and ≥65 years.

Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination.

Background: NVX-CoV2373 is an efficacious coronavirus disease 2019 (COVID-19) vaccine comprising full-length recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (rS) glycoprotein and Matrix-M adjuvant. Phase 2 of a randomized, placebo-controlled, phase 1/2 trial in healthy adults (18-84 years of age) previously reported good safety/tolerability and robust humoral immunogenicity.

Methods: Participants were randomized to placebo or 1 or 2 doses of 5-µg or 25-µg rS with 50 µg Matrix-M adjuvant 21 days apart.

Efficacy of mRNA-1273 and Novavax ancestral or BA.1 spike booster vaccines against SARS-CoV-2 BA.5 infection in nonhuman primates.

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.

The Matrix-M™ adjuvant: A critical component of vaccines for the 21 century.

Matrix-M™ adjuvant is a key component of several novel vaccine candidates. The Matrix-M adjuvant consists of two distinct fractions of saponins purified from the Molina tree, combined with cholesterol and phospholipids to form 40-nm open cage-like nanoparticles, achieving potent adjuvanticity with a favorable safety profile. Matrix-M induces early activation of innate immune cells at the injection site and in the draining lymph nodes.

Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents: A Randomized Clinical Trial.

Importance: Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.

Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants.

SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.

Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This assay measures the inhibition of SARS-CoV-2 spike (S) protein binding to the receptor, hACE2, by serum from vaccine clinical trials.

Novavax NVX-COV2373 triggers neutralization of Omicron sub-lineages.

The SARS-CoV-2 Omicron (B.1.1.

Antibody Correlates of Protection From Severe Respiratory Syncytial Virus Disease in a Vaccine Efficacy Trial.

Background: Respiratory syncytial virus (RSV) can cause serious lung infections in young children and there is currently no available vaccine.

Methods: We used complementary statistical frameworks to analyze 4 RSV serology measurements in mothers and their infants in South Africa who participated in a phase 3 maternal immunization trial of an RSV F protein nanoparticle vaccine as correlates of risk and of protection against different RSV disease endpoints.

Results: We found evidence to support each antibody measurement-encompassing RSV-neutralizing antibodies and F surface glycoprotein-binding antibodies-as an inverse correlate of risk of RSV-associated acute lower respiratory tract infection with severe hypoxia in at least 1 framework, with vaccine-induced fold-rise from the maternal enrollment to day 14 samples of anti-F immunoglobulin G (IgG) binding antibodies having the most consistent evidence.

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial.

Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover.