Publications by authors named "Darin K Edwards"
Current COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth understanding of the antigenic and immunogenic properties of available vaccines. Here we examined the antigenicity of two of the original COVID-19 vaccines, mRNA-1273 and NVX-CoV2373, by electron microscopy-based polyclonal epitope mapping (EMPEM) of serum from immunized non-human primates (NHPs) and clinical trial donors.
View Article and Find Full Text PDFSARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization.
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- A study examined the effects of mRNA vaccine boosting (ipsilateral vs. contralateral leg) in mice after initial vaccination, with a focus on immune responses against SARS-CoV-2 variants.
- Both boosting sites resulted in similar levels of antibody responses and immune cell activation, indicating no significant difference.
- Overall, the findings suggest that where the vaccine is injected (same side or opposite leg) does not significantly affect immune protection against the Omicron BA.1 variant.
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- Vaccines have helped reduce COVID-19 severity, but their effectiveness in areas with helminth infections, like the roundworm Hpb, isn't fully understood.
- In a study involving mice, it was found that while B cell responses were similar in both Hpb-infected and uninfected mice post-vaccination, T cell responses were significantly weaker in those infected with Hpb.
- The presence of Hpb compromised the ability of the vaccine to protect against variant strains of SARS-CoV-2, indicating that helminth infections can negatively affect vaccine responses through an IL-10 mediated pathway.
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- Researchers studied how mRNA vaccine boosters affect antibody responses in both mice and humans, finding that initial vaccine doses influenced responses to newer variants.
- In humans, receiving Omicron-matched boosters after prior vaccinations led to a broadened antibody response, suggesting that imprinting can promote the production of antibodies that are effective against various SARS-CoV-2 variants and related viruses.
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- This study focuses on understanding how mRNA-based vaccines, specifically mRNA-1273, generate immune responses by examining the antibody epitope profiles in response to the SARS-CoV-2 spike protein.
- Researchers analyzed serum samples from clinical trial participants who received the mRNA-1273 vaccine, both after the primary series and following a booster dose, to identify specific antibody responses.
- Findings revealed that while initial antibody signals decreased over time, they significantly increased again after a booster, and certain booster formulations, like variant-updated vaccines, resulted in stronger antibody responses compared to the original mRNA-1273 booster.
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- Monovalent and bivalent COVID-19 vaccines containing the Omicron XBB.1.5 variant were approved for use during the 2023-2024 immunization season and are currently undergoing evaluation in a phase 2/3 study.
- Among participants who previously received previous vaccine doses, those who received the monovalent vaccine showed greater increases in neutralizing antibodies against various SARS-CoV-2 variants compared to those who received the bivalent vaccine.
- The results indicate that the XBB.1.5 mRNA vaccines generate strong immune responses against newer variants, validating the update of COVID-19 vaccines to include the XBB.1.5 spike protein.
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- The study investigates how helminth (hookworm) infection affects the effectiveness of an mRNA vaccine designed to fight COVID-19 in mice.
- While both infected and uninfected mice showed strong antibody responses, the T cell responses were significantly weaker in the helminth-infected group.
- The presence of the helminth reduced the vaccine's ability to control newer COVID-19 variants, suggesting that helminth infections can impair vaccine-induced T cell immunity through an IL-10 mediated pathway.
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- SARS-CoV-2 variants are evolving, making it crucial to test updated vaccines on non-human primates to improve human clinical practice.
- Researchers conducted a study on mRNA-1273 vaccination in rhesus macaques, examining both innate and adaptive immune responses using single-cell sequencing.
- They found that the second vaccine dose increased specific immune cells and gene expression linked to better antibody production, highlighting the interaction between innate and adaptive immunity.
Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)-lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding [immunoglobulin G (IgG) and IgA] and neutralizing antibodies.
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- The study explores new mRNA vaccine strategies to enhance effectiveness against COVID-19, focusing on specific protein domains of the virus instead of the full-length spike protein.
- The candidate vaccine mRNA-1283, combining the N-terminal domain and receptor binding domain, shows better antigen expression, stronger antibody responses, and improved stability compared to existing vaccines.
- In animal tests, mRNA-1283 elicits equal or greater immune protection against various COVID-19 variants, supporting its advancement to clinical trials for further evaluation.
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- A phase 2/3 trial compared the safety and effectiveness of the new bivalent mRNA-1273.222 vaccine, targeting Omicron BA.4/BA.5 variants, against the original mRNA-1273 vaccine used as boosters in adults who had previously received it.
- Results showed that the bivalent vaccine produced stronger neutralizing antibody responses against the Omicron variants while maintaining similar effectiveness against the original virus compared to mRNA-1273.
- The safety profile for mRNA-1273.222 was consistent with the previous vaccine, with no new safety issues found, but further monitoring of vaccine effectiveness and potential new variants is advised.
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- A phase 2/3 study compared the efficacy and safety of the Omicron-BA.1 bivalent vaccine (mRNA-1273.214) to the original booster (mRNA-1273) in adults who had previously received two doses of an mRNA vaccine.
- Day 91 results showed that mRNA-1273.214 produced significantly higher neutralizing antibody levels against Omicron-BA.1 compared to mRNA-1273 and had comparable responses to the ancestral SARS-CoV-2 virus.
- Both vaccines had similar safety profiles, but the Omicron-BA.1 bivalent vaccine demonstrated better antibody responses across various variants, indicating its potential advantages as a booster.
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- * Vaccine-induced antibodies interact with Fc gamma receptors (FcγRs) and have been linked to better clinical outcomes, although a direct cause-and-effect relationship hasn't been confirmed.
- * Research using mouse models shows that effective immune response against SARS-CoV-2 variants, including Omicron, relies on FcγR engagement and the presence of alveolar macrophages for proper antibody-mediated protection.
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- - Emerging SARS-CoV-2 variants show antigenic changes in the spike protein that make them less susceptible to antibodies from vaccines like mRNA-1273 and BNT162b2, but these vaccines still protect against severe illness and death.
- - The study investigates the role of Fc gamma receptors (FcγRs) in mediating antibody protection against infection, finding that vaccine-induced antibodies need Fc effector functions for effective neutralization of new variants.
- - Research on mice reveals that without specific FcγRs and alveolar macrophages, the protective effects of the mRNA-1273 vaccine against variants like Omicron BA.5 are significantly reduced, highlighting the importance of these immune components in vaccine efficacy.
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- The FDA authorized BNT162b2 and mRNA-1273 vaccines for infants 6 months and older in June 2022, but concerns about their long-term efficacy against new variants remain.
- Previous studies shown that specific vaccine formulations were safe and effective in infant rhesus macaques, demonstrating persistent antibody responses for 12 months.
- When challenged with the Delta variant, vaccinated macaques showed better viral clearance and milder symptoms compared to unvaccinated ones, suggesting that early-life vaccination against SARS-CoV-2 can be beneficial.
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- * Researchers tested two new bivalent vaccines (mRNA-1273.214 and mRNA-1273.222) in mice and found they produced stronger antibody responses against Omicron variants compared to the original vaccine.
- * Administering these bivalent vaccines as boosters significantly improved immune protection and reduced lung infection severity in mice, highlighting their potential effectiveness against circulating strains.
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- The emergence of SARS-CoV-2 variants in the Omicron lineage has led to reduced vaccine effectiveness and ongoing virus transmission due to the spike protein's ability to evade antibodies.
- Researchers evaluated two bivalent vaccines that include mRNAs for spike proteins from both the original virus and recent variants (BA.1 or BA.4/5) and found they produced stronger immune responses in mice compared to existing monovalent vaccines.
- When used as a booster after initial vaccination, these bivalent vaccines not only generated a more robust antibody response but also provided greater protection against BA.5 infections and reduced inflammation in the lungs.
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- Researchers developed a new mRNA vaccine, mRNA-1283, targeting specific spike protein domains of the virus responsible for COVID-19.
- This vaccine demonstrated enhanced antigen expression, antibody responses, and stability when stored in refrigerated conditions compared to the existing mRNA-1273 vaccine.
- In preclinical tests, mRNA-1283 provided similar or better immune protection against various COVID-19 variants in mice, indicating its potential for human clinical trials.
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- Updated immunization strategies are crucial to combat different variants of SARS-CoV-2, leading to a trial for a bivalent vaccine (mRNA-1273.211) targeting both ancestral and Beta variant spike proteins.
- The trial included two booster doses (50-µg and 100-µg) given about 9 months after initial vaccination, focusing on comparing safety, reactogenicity, and antibody responses to previous doses.
- Results showed that the bivalent booster elicited significantly higher neutralizing antibody responses against various variants, matched the safety profile of prior boosters, and indicated a strong protective potential against COVID-19.
Background: The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known.
Methods: In this ongoing, phase 2-3 study, we compared the 50-μg bivalent vaccine mRNA-1273.
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- The rise of SARS-CoV-2 in 2019 prompted the creation of numerous vaccines, with several now approved for human use.
- Monitoring how well these vaccines generate antibody responses against new variants is crucial for shaping public health strategies.
- Research indicates that neutralizing antibody responses in vaccinated mice are not as effective or representative as those in humans or non-human primates, highlighting possible limitations of using mice in these studies.
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- mRNA-based vaccines have gained recognition over the past 20 years for being effective and well-tolerated in fighting infectious diseases.
- Their significant impact was highlighted during the COVID-19 pandemic, where they were quickly developed and demonstrated high effectiveness with good safety profiles.
- The review discusses current technologies, ongoing clinical studies, and future possibilities for mRNA vaccines, showcasing their potential to tackle various pathogens and complex antigens.
Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune-evasion properties have arisen, which could jeopardize recently deployed vaccine- and antibody-based countermeasures.
Methods: Here, we evaluated in mice and hamsters the efficacy of a pre-clinical version of the Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.
The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.
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