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| Open AccessNeutralization, effector function and immune imprinting of Omicron variants
Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.
- Amin Addetia
- , Luca Piccoli
- & David Veesler
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Article
| Open AccessAlgorithm for optimized mRNA design improves stability and immunogenicity
An algorithm based on concepts established in computational linguistics enables rapid principled design of mRNA vaccines optimizing both structural stability and codon usage, resulting in improved half-life, protein expression and immune responses.
- He Zhang
- , Liang Zhang
- & Liang Huang
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SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
COVID-19 booster immunizations aimed at spike protein from new SARS-CoV-2 variants induce robust germinal centre B cell responses against the original spike protein, as well as de novo B cell responses against the variant spike protein.
- Wafaa B. Alsoussi
- , Sameer Kumar Malladi
- & Ali H. Ellebedy
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| Open AccessAntibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination
Pre-existing high-affinity antibodies alter germinal centre and memory B cell selection by lowering the activation threshold for B cells and through direct masking of their cognate epitopes, thereby permitting a diverse set of abundant lower-affinity clones targeting alternate epitopes to participate in the immune response.
- Dennis Schaefer-Babajew
- , Zijun Wang
- & Michel C. Nussenzweig
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Article
| Open AccessIncreased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost
A third dose of an mRNA vaccine against SARS-CoV-2 results in an expanded B cell repertoire that produces antibodies with increased potency and breadth.
- Frauke Muecksch
- , Zijun Wang
- & Michel C. Nussenzweig
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Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron
Sera from unvaccinated, vaccinated, and previously infected and vaccinated individuals show reduced neutralizing and spike protein-binding activity towards the Omicron (B.1.1.529) variant of SARS-CoV-2 compared to other variants.
- Juan Manuel Carreño
- , Hala Alshammary
- & Florian Krammer
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Article
| Open AccessOptimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
CV2CoV, a second-generation mRNA COVID-19 vaccine with non-modified nucleosides but optimized non-coding regions, is demonstrated to be effective against SARS-CoV-2 challenge when tested in non-human primates.
- Makda S. Gebre
- , Susanne Rauch
- & Dan H. Barouch
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Immunogenicity and efficacy of heterologous ChAdOx1–BNT162b2 vaccination
An observational study of more than 13,000 healthcare workers shows that a prime–boost vaccine regimen of AstraZeneca ChAdOx1-S-nCoV-19 with Pfizer BNT162b2 provides enhanced protection against SARS-CoV-2 infection compared with two doses of BNT162b2.
- Bruno Pozzetto
- , Vincent Legros
- & Sophie Trouillet-Assant
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Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Immune analyses against circulating SARS-CoV-2 variants show that mRNA vaccination induces robust neutralizing antibodies and boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.
- Carolina Lucas
- , Chantal B. F. Vogels
- & Akiko Iwasaki
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Article
| Open AccessRapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine
Longitudinal analyses of SARS-CoV-2 mRNA vaccine-elicited epitope-specific CD8+ T cell responses shows that CD8+ T cells are rapidly induced after prime vaccination and stably maintained after boost vaccination.
- Valerie Oberhardt
- , Hendrik Luxenburger
- & Maike Hofmann
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Systems vaccinology of the BNT162b2 mRNA vaccine in humans
Profiling the immune responses of 56 volunteers vaccinated with BNT162b2 reveals how this mRNA vaccine primes the innate immune system to mount a potent response to SARS-CoV-2 after booster immunization.
- Prabhu S. Arunachalam
- , Madeleine K. D. Scott
- & Bali Pulendran
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SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses
Analysis of antigen-specific B cells in lymph nodes of individuals vaccinated with BNT162b2 reveals lasting germinal centre responses, explaining the robust humoral immunity induced by SARS-CoV-2 mRNA-based vaccines.
- Jackson S. Turner
- , Jane A. O’Halloran
- & Ali H. Ellebedy
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BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants
Samples of serum from individuals immunized with the BNT162b2 vaccine show neutralization activity against engineered SARS-CoV-2s bearing the spike mutations from B.1.617 and other variants.
- Jianying Liu
- , Yang Liu
- & Pei-Yong Shi
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Article |
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses
Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.
- Kevin O. Saunders
- , Esther Lee
- & Barton F. Haynes
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BNT162b vaccines protect rhesus macaques from SARS-CoV-2
BNT162b1 and BNT162b2 are two candidate mRNA vaccines against COVID-19 that elicit high virus-entry inhibition titres in mice, elicit high virus-neutralizing titres in rhesus macaques and protect macaques from SARS-CoV-2 challenge.
- Annette B. Vogel
- , Isis Kanevsky
- & Ugur Sahin
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SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness
mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.
- Kizzmekia S. Corbett
- , Darin K. Edwards
- & Barney S. Graham
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An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma
Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4+ and CD8+ T-cell immunity.
- Ugur Sahin
- , Petra Oehm
- & Özlem Türeci
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Letter |
Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination
A single, low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA encoding the pre-membrane and envelope glycoproteins of Zika virus protects both mice and rhesus macaques against infection and elicits rapid and long-lasting neutralizing antibody responses.
- Norbert Pardi
- , Michael J. Hogan
- & Drew Weissman
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Letter |
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
The development of a nanoparticle RNA vaccine is reported that preferentially targets dendritic cells after systemic administration, and is shown to provide durable interferon-α-dependent antigen-specific immunity in mouse tumour models; initial results in advanced melanoma patients indicate potential efficacy in humans.
- Lena M. Kranz
- , Mustafa Diken
- & Ugur Sahin