mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

Gagné, Matthew; Moliva, Juan I.; Foulds, Kathryn E.; Andrew, Shayne F.; Flynn, Barbara J.; Werner, Anne P.; Wagner, Danielle A.; Teng, I-Ting; Lin, Bob C.; Moore, Christopher; Jean-Baptiste, Nazaire; Carroll, R. N. P.; Foster, Stephanie L.; Patel, Mit; Ellis, Madison; Edara, Venkata-Viswanadh; Maldonado, Nahara Vargas; Minai, Mahnaz; McCormick, Lauren; Honeycutt, Christopher Cole; Nagata, Bianca M.; Bock, Kevin W.; Dulan, Caitlyn N M; Cordon, Jamilet; Flebbe, Dillon R.; Todd, John-Paul M.; McCarthy, Elizabeth; Pessaint, Laurent; Ry, Alex Van; Narvaez, Brandon; Valentin, Daniel; Cook, Anthony; Dodson, Alan; Steingrebe, Katelyn; Nurmukhambetova, Saule; Godbole, Sucheta; Henry, Amy R.; Laboune, Farida; Roberts-Torres, Jesmine; Lorang, Cynthia G.; Amin, Shivani; Trost, Jessica F.; Naisan, Mursal; Basappa, Manjula; Willis, Jacquelyn; Wang, Lingshu; Shi, Wei; Doria‐Rose, Nicole A.; Zhang, Yi; Yang, Eun Sung; Leung, Kwanyee; O’Dell, Sijy; Schmidt, Stephen D.; Olia, Adam S.; Liu, Cuiping; Harris, Darcy R.; Chuang, Gwo-Yu; Stewart‐Jones, Guillaume; Renzi, Isabella; Lai, Yen‐Ting; Malinowski, Agata; Wu, Kai; Mascola, John R.; Carfı́, Andrea; Kwong, Peter D.; Edwards, Darin K.; Lewis, Mark G.; Andersen, Hanné; Corbett, Kizzmekia S.; Nason, Martha; McDermott, Adrian B.; Suthar, Mehul S.; Moore, Ian N.; Roederer, Mario; Sullivan, Nancy J.; Douek, Daniel C.; Seder, Robert A.

doi:10.1016/j.cell.2022.03.038

Cited by 198 publications

(201 citation statements)

References 88 publications

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“…It will be interesting to see how the field utilizes this matrix of probes–individually, such as with the Omicron spike or RBD, as a series, such as assessing sera with RBDs from Alpha through Omicron, or as a matrix. For instance, we have provided WA-1, Beta, Delta, and Omicron probes for confirming elicitation of cross-reactive B cells by mRNA-1273 or mRNA-Omicron boost and for evaluating their ACE2 binding inhibition [ 44 ]. Another recent research identified convergent immune responses elicited by Beta- or Gamma-infection when compared to ancestral virus infection using S2P, RBD, and NTD probes from WA-1, Beta, and Gamma variants [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

et al. 2022

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Since the outbreak of the COVID-19 pandemic, widespread infections have allowed SARS-CoV-2 to evolve in human, leading to the emergence of multiple circulating variants. Some of these variants show increased resistance to vaccine-elicited immunity, convalescent plasma, or monoclonal antibodies. In particular, mutations in the SARS-CoV-2 spike have drawn attention. To facilitate the isolation of neutralizing antibodies and the monitoring of vaccine effectiveness against these variants, we designed and produced biotin-labeled molecular probes of variant SARS-CoV-2 spikes and their subdomains, using a structure-based construct design that incorporated an N-terminal purification tag, a specific amino acid sequence for protease cleavage, the variant spike-based region of interest, and a C-terminal sequence targeted by biotin ligase. These probes could be produced by a single step using in-process biotinylation and purification. We characterized the physical properties and antigenicity of these probes, comprising the N-terminal domain (NTD), the receptor-binding domain (RBD), the RBD and subdomain 1 (RBD-SD1), and the prefusion-stabilized spike ectodomain (S2P) with sequences from SARS-CoV-2 variants of concern or of interest, including variants Alpha, Beta, Gamma, Epsilon, Iota, Kappa, Delta, Lambda, Mu, and Omicron. We functionally validated probes by using yeast expressing a panel of nine SARS-CoV-2 spike-binding antibodies and confirmed sorting capabilities of variant probes using yeast displaying libraries of plasma antibodies from COVID-19 convalescent donors. We deposited these constructs to Addgene to enable their dissemination. Overall, this study describes a matrix of SARS-CoV-2 variant molecular probes that allow for assessment of immune responses, identification of serum antibody specificity, and isolation and characterization of neutralizing antibodies.

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Section: Discussionmentioning

confidence: 99%

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

et al. 2022

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“…For full protection, antibodies against SARS-CoV-2 WT and Omicron might be needed. However, a boost with an Omicron-specific mRNA vaccine after a WT mRNA vaccination did not provide enhanced immune responses or protection compared to a WT-specific boost in non-human primates [ 50 ]. On the other hand, a chimeric mRNA vaccine encoding a chimera of the Delta-RBD variant and the entire S antigen of Omicron induced potent and broadly neutralizing antibodies against Omicron (both BA.1 and BA.2) and Delta in mice [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of Coronavirus-Neutralizing Activity in COVID-19 Patients

Hastert

Henß

Rhein

et al. 2022

Viruses

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has now been continuing for more than two years. The infection causes COVID-19, a disease of the respiratory and cardiovascular system of variable severity. Here, the humoral immune response of 80 COVID-19 patients from the University Hospital Frankfurt/Main, Germany, was characterized longitudinally. The SARS-CoV-2 neutralization activity of serum waned over time. The neutralizing potential of serum directed towards the human alpha-coronavirus NL-63 (NL63) also waned, indicating that no cross-priming against alpha-coronaviruses occurred. A subset of the recovered patients (n = 13) was additionally vaccinated with the mRNA vaccine Comirnaty. Vaccination increased neutralization activity against SARS-CoV-2 wild-type (WT), Delta, and Omicron, although Omicron-specific neutralization was not detectable prior to vaccination. In addition, the vaccination induced neutralizing antibodies against the more distantly related SARS-CoV-1 but not against NL63. The results indicate that although SARS-CoV-2 humoral immune responses induced by infection wane, vaccination induces a broad neutralizing activity against multiple SARS-CoVs, but not to the common cold alpha-coronavirus NL63.

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“…When macaques were boosted with either the standard Moderna mRNA or an Omicron‐adapted mRNA, comparable neutralizing antibody titres against WT and Omicron were observed in both cases. Both boosters increased the breadth of the antibody response (Gagne et al ., 2022 ). Macaques which were boosted with the Pfizer mRNA vaccine and were subsequently challenged with Omicron controlled rapidly viral replication in the lower respiratory tract.…”

Section: The Futurementioning

confidence: 99%

COVID‐19: Omicron – the latest, the least virulent, but probably not the last variant of concern of SARS‐CoV‐2

Brüssow

2022

Microbial Biotechnology

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Summary The Omicron variant rapidly became the dominant SARS‐CoV‐2 strain in South Africa and elsewhere. This review explores whether this rise was due to an increased transmission of the variant or its escape from population immunity by an extensively mutated spike protein. The mutations affected the structure of the spike protein leading to the loss of neutralization by most, but not all, therapeutic monoclonal antibodies. Omicron also shows substantial immune escape from serum antibodies in convalescent patients and vaccinees. A booster immunization increased, however, the titre and breadth of antiviral antibody response. The cellular immune response against Omicron was largely preserved explaining a satisfying protection of boosted vaccinees against severe infections. Clinicians observed less severe infection with Omicron, but other scientists warned that this must not necessarily reflect less intrinsic virulence. However, in animal experiments with mice and hamsters, Omicron infections also displayed a lesser virulence than previous VOCs and lung functions were less compromised. Cell biologists demonstrated that Omicron differs from Delta by preferring the endocytic pathway for cell entry over fusion with the plasma membrane which might explain Omicron’s distinct replication along the respiratory tract compared with Delta. Omicron represents a distinct evolutionary lineage that deviated from the mainstream of evolving SARS‐CoV‐2 already in mid‐2020 raising questions about where it circulated before getting widespread in December 2021. The role of Omicron for the future trajectory of the COVID‐19 pandemic is discussed.

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mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

Cited by 198 publications

References 88 publications

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

Longitudinal Analysis of Coronavirus-Neutralizing Activity in COVID-19 Patients

COVID‐19: Omicron – the latest, the least virulent, but probably not the last variant of concern of SARS‐CoV‐2

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