mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against 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; Todd, John-Paul M.; McCarthy, Elizabeth; Pessaint, Laurent; Ry, Alex Van; Narvaez, Brandon; Valentin, Daniel; Cook, Anthony; Dodson, Alan; Steingrebe, Katelyn; Flebbe, Dillon R.; 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.; Olia, Adam S.; Liu, Cuiping; Harris, Darcy R.; Carfı́, Andrea; Mascola, John R.; Kwong, Peter D.; Edwards, Darin K.; Andersen, Hanné; Lewis, Mark G.; 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:10.1101/2022.02.03.479037

Cited by 56 publications

(78 citation statements)

References 91 publications

(123 reference statements)

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“…However, our data argued that the heterologous booster scheme is not superior to boosting with the ancestral WA mRNA in terms of establishing immunity against Omicron ( Figure 5E ). Similar conclusion was drawn by a research group from NIH, when they challenged mRNA-1273-vaccinated macaques with live omicron virus 31 . A plausible explanation is although Omicron S protein has ~35 mutations, it still exhibits 97% similarity to the ancestral WA strain in the amino acid sequence.…”

Section: Discussionsupporting

confidence: 77%

Chimeric mRNA based COVID-19 vaccine induces protective immunity against Omicron and Delta

Zhao

Shaabani

et al. 2022

Preprint

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The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines currently in use. Here, we explored various strategies to develop mRNA vaccines that offer potentially safer and wider coverage of VOCs. The initial mouse vaccination results showed that the individual VOC mRNAs carrying furin cleavage mutation induced the generation of neutralizing antibody in a VOC-specific manner. Moreover, we discovered that the antibodies produced from mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs cross-reacted with other VOCs. The broad spectrum of generated nAb was further confirmed when vaccinated mice were challenged with the respective live viruses. However, neither WA-Furin nor Beta-Furin mRNA elicited potent neutralizing activity against the omicron variant. Interestingly, in a mix-and-match booster experiment, omicron-Furin and WA-Furin mRNA elicited comparable protection against omicron. Finally, we tested the concept of bivalent vaccine by introducing the RBD of Delta strain into the intact S antigen of Omicron. The chimeric mRNA induces potent and broadly acting nAb against Omicron and Delta, which paves the way to develop vaccine candidate to target emerging variants in the future.

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Section: Discussionsupporting

confidence: 77%

Chimeric mRNA based COVID-19 vaccine induces protective immunity against Omicron and Delta

Zhao

Shaabani

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…However, Omicron-mRNA boost in vaccinated macaques has not displayed significantly different NAb titers and B cells response 24 . This could be due to different immunization intervals and antigen epitopes.…”

Section: Discussionmentioning

confidence: 88%

“…As a booster with Omicron-matched DNA vaccines, increased width of immune response has been observed 23 . However, in macaque models, vaccination with Omicron-specific boosters do not increase neutralizing antibody (NAb) titers against Omicron and remain the equivalent levels of B cell response 24 . Of note, both two types of vaccines were designed according to full-length spike proteins.…”

Section: Introductionmentioning

confidence: 99%

Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine booster

Peng

Feng

et al. 2022

Preprint

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With the development of COVID-19, even though increased global vaccination coverage, a super variant of SARS-CoV-2, Omicron, carrying a great number of mutations, has been verified its strong capacity of immune escape. An increased risk of SARS-CoV-2 reinfection or breakthrough infection should be concerned. We analyzed the humoral immune response of Omicron breakthrough infection and found its cross-neutralization against VOCs. We established mouse models to verify whether Omicron-specific RBD subunit boost immune response by immunizing Omicron-RBD recombinant proteins. The results suggest that an additional boost vaccination with Omicron-RBD protein could increase humoral immune response against both WT and current VOCs.

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“…Critically, our results provided explicit evidence that Omicron can drastically attenuate its antigenicity across all epitopes on the RBD, which is the key target by neutralizing antibodies. During our manuscript preparation, a preprint reported that an Omicron-specific mRNA vaccine boost appears to provide inferior protection against Omicron infection in non-human primates compared to boost using the WT mRNA vaccine 20 . Moreover, new clinical data suggested that the antibody titers after Omicron breakthrough cases were lower than those of after Delta infection [2][3][4][5][6][7][8] .…”

Section: Discussionmentioning

confidence: 99%

Reduced antigenicity of Omicron lowers host serologic response

Tubiana

Xiang

Fan

et al. 2022

Preprint

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SARS-CoV-2 Omicron variant of concern (VOC) contains fifteen mutations on the receptor binding domain (RBD), evading most neutralizing antibodies from vaccinated sera. Emerging evidence suggests that Omicron breakthrough cases are associated with substantially lower antibody titers than other VOC cases. However, the mechanism remains unclear. Here, using a novel geometric deep-learning model, we discovered that the antigenic profile of Omicron RBD is distinct from the prior VOCs, featuring reduced antigenicity in its remodeled receptor binding sites (RBS). To substantiate our deep-learning prediction, we immunized mice with different recombinant RBD variants and found that the Omicron's extensive mutations can lead to a drastically attenuated serologic response with limited neutralizing activity in vivo, while the T cell response remains potent. Analyses of serum cross-reactivity and competitive ELISA with epitope-specific nanobodies revealed that the antibody response to Omicron was reduced across RBD epitopes, including both the variable RBS and epitopes without any known VOC mutations. Moreover, computational modeling confirmed that the RBS is highly versatile with a capacity to further decrease antigenicity while retaining efficient receptor binding. Longitudinal analysis showed that this evolutionary trend of decrease in antigenicity was also found in hCoV229E, a common cold coronavirus that has been circulating in humans for decades. Thus, our study provided unprecedented insights into the reduced antibody titers associated with Omicron infection, revealed a possible trajectory of future viral evolution and may inform the vaccine development against future outbreaks.

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mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron

Cited by 56 publications

References 91 publications

Chimeric mRNA based COVID-19 vaccine induces protective immunity against Omicron and Delta

Chimeric mRNA based COVID-19 vaccine induces protective immunity against Omicron and Delta

Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine booster

Reduced antigenicity of Omicron lowers host serologic response

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