Publications by authors named "Sayda Elbashir"
Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in young children and older adults. We designed a codon-optimized mRNA vaccine, mRNA-1345, encoding the RSV F-glycoprotein stabilized in the prefusion (preF) conformation and with a deletion at the cytoplasmic tail. mRNA-1345 cell surface protein expression was higher and detected for longer versus previous mRNA-based RSV vaccine candidates evaluated clinically.
View Article and Find Full Text PDFMessenger RNA (mRNA) has emerged as a highly effective and versatile platform for vaccine delivery. We previously designed a virus-like particle (VLP)-forming mRNA vaccine against human immunodeficiency virus-1 (HIV-1) that elicited envelope-specific neutralizing antibodies and protection from heterologous simian-human immunodeficiency virus (SHIV) infection in rhesus macaques. Here, we introduce a key technological advance to this platform by inclusion of mRNA encoding a retroviral protease to process Gag and produce mature VLPs.
View Article and Find Full Text PDFThe continued diversification of SARS-CoV-2 omicron lineage has given rise to the JN.1 variant and descendant strains (KP.2, KP.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates how antiviral monoclonal antibodies (mAbs), particularly casirivimab and imdevimab (CAS+IMD), affect immune responses when individuals are vaccinated against SARS-CoV-2 after receiving mAb treatment.
- It was found that the presence of CAS+IMD during vaccination reduced the effectiveness of the vaccine in generating neutralizing antibodies, though other immune responses remained intact.
- This reduction in antibody production is linked to "epitope masking," but can be reversed with booster shots, and influences the immune response differently in those who had not yet begun their natural immunity when treated with mAbs.
Article Synopsis
- 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.
Article Synopsis
- 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.
Article Synopsis
- 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.
Article Synopsis
- 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.
Article Synopsis
- 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.
Article Synopsis
- For vaccines to provide long-lasting immunity and effectiveness, they often require a multi-dose schedule that primes the immune system and boosts its response through repeated doses.
- During the COVID-19 pandemic, 2-dose vaccination regimens were often administered with short intervals to offer quick protection, but studies indicate that longer intervals between doses might enhance immunity durability.
- Research on the mRNA-1273 vaccine in mice found that intervals of 6 to 8 weeks between doses led to higher antibody levels and stronger immune responses, suggesting that longer dosing intervals could be beneficial in non-pandemic contexts.
Monoclonal antibodies have been used successfully as recombinant protein therapy; however, for HIV, multiple broadly neutralizing antibodies may be necessary. We used the mRNA-LNP platform for in vivo co-expression of 3 broadly neutralizing antibodies, PGDM1400, PGT121, and N6, directed against the HIV-1 envelope protein. mRNA-encoded HIV-1 antibodies were engineered as single-chain Fc (scFv-Fc) to overcome heavy- and light-chain mismatch.
View Article and Find Full Text PDFArticle Synopsis
- * 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.
Article Synopsis
- 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.
Article Synopsis
- 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.
Article Synopsis
- 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.
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.
View Article and Find Full Text PDFThe development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in inducing neutralizing antibodies.
View Article and Find Full Text PDFProtective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains.
Sci Transl Med
February 2022
Although mRNA vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent COVID-19, the emergence of new viral variants jeopardizes their efficacy. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike protein) or modified (mRNA-1273.351, designed for B.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity.
View Article and Find Full Text PDFAlthough mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.
View Article and Find Full Text PDFB.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization.
View Article and Find Full Text PDFBackground: Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity.
View Article and Find Full Text PDF