Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2

Peng, Lei; Renauer, Paul; Ökten, Arya; Fang, Zhenhao; Park, Jonathan J.; Zhou, Xiaoyu; Lin, Qianqian; Dong, Matthew B.; Filler, Renata; Xiong, Qiancheng; Clark, Paul; Lin, Chenxiang; Wilen, Craig B.; Chen, Sidi

doi:10.1016/j.xcrm.2022.100634

Cited by 12 publications

(11 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They showed a higher level of Beta-specific neutralization in mice receiving a high dose of Beta-based vaccine. Interestingly, another mRNA vaccine study showed improved neutralization against Reference or Delta when immunized with the corresponding spike sequence, but no significant improvement with Beta mRNA 20 . Both groups illustrated that all vaccine types were able to protect mice from challenge with Reference, Beta, and Delta VOC.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern

et al. 2022

View full text Add to dashboard Cite

Using our strongly immunogenic SmT1 SARS-CoV-2 spike antigen platform, we developed antigens based on the Beta & Delta variants of concern (VOC). These antigens elicited higher neutralizing antibody activity to the corresponding variant than comparable vaccine formulations based on the original reference strain, while a multivalent vaccine generated cross-neutralizing activity in all three variants. This suggests that while current vaccines may be effective at reducing severe disease to existing VOC, variant-specific antigens, whether in a mono- or multivalent vaccine, may be required to induce optimal immune responses and reduce infection against arising variants.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The substantial differences between WT and Omicron spikes lead to extensive immune escape of Omicron from WT mRNA vaccine 4 , which prompted the idea of developing Omicron-specific vaccines. We generated several COVID-19 variant-specific mRNA vaccine candidates (including Omicron BA.1) 5 , 6 which were designed based on variants’ spike stabilized by six proline mutations 7 . Variant-specific vaccine candidates, or lipid nanoparticle (LNP)-mRNAs, unequivocally exhibited advantage over WT LNP-mRNA in terms of eliciting neutralizing antibody against cognate antigens 5 , 6 .…”

mentioning

confidence: 99%

“…We generated several COVID-19 variant-specific mRNA vaccine candidates (including Omicron BA.1) 5 , 6 which were designed based on variants’ spike stabilized by six proline mutations 7 . Variant-specific vaccine candidates, or lipid nanoparticle (LNP)-mRNAs, unequivocally exhibited advantage over WT LNP-mRNA in terms of eliciting neutralizing antibody against cognate antigens 5 , 6 . Moreover, immune profiling of Omicron BA.1 LNP-mRNA showed a significant boosting effect on waning immunity of WT LNP-mRNA-vaccinated mice to both Delta and Omicron BA.1 variants.…”

mentioning

confidence: 99%

“…To answer these questions, we characterized the antibody response induced by WT or variant specific LNP-mRNAs to Omicron BA.2 and compared it with immune response to BA.1. Samples used for BA.2 characterization were collected from mice that received two doses of 1 µg WT, B.1.351 (Beta variant) or B.1.617 (ancestor to the Delta variant (lineage B.1.617.2)) LNP-mRNAs 6 . All three LNP-mRNAs elicited significant antibody response to BA.2 (Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2

Fang

Peng²,

Lucas³

et al. 2022

Cell Discov

Self Cite

View full text Add to dashboard Cite

“…The WT and Delta spike plasmids were cloned in our previous study 7, 8 . BA.2 spike plasmid was cloned based on the isolate sequencing data in GISAID EpiCoV (EPI_ISL_6795834.2) 9 .…”

Section: Methodsmentioning

confidence: 99%

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron subvariants BA.2, BA.2.12.1 and BA.5

Fang

Chen

2022

Preprint

Self Cite

View full text Add to dashboard Cite

As the immune protection conferred by first booster shot wanes over time and new Omicron subvariant emerges with stronger immune evasion, the need for variant-adapted COVID vaccine booster is increasingly imminent. However, the rapid replacement of dominant Omicron subvariants (from BA.1 to BA.2, then BA.2.12.1 and now BA.4/5) poses a great challenge to update COVID vaccine targeting the fast-evolving variants while maintaining potency against existing variants. It is a crucial question to ask which variant-based antigen(s) to use in the next generation COVID vaccine to elicit potent and broad response to past, present, and potential rising variants. Bivalent vaccine candidates have been under active clinical testing such as Modern mRNA-1273.214. In this study, we generate a Delta + BA.2 bivalent mRNA vaccine candidate and tested in animals. We compare the antibody response elicited by ancestral (wild type, WT), Delta, BA.2 spike based monovalent or Delta & BA.2 bivalent mRNA boosters against Omicron BA.2, BA.2.12.1 and BA.4/5 subvariants. In mice pre-immunized with two doses of WT lipid nanoparticle mRNA (LNP-mRNA), all three monovalent and one bivalent boosters elevated Omicron neutralizing antibody titers to various degree. The boosting effect of Delta and BA.2 specific monovalent or bivalent LNP-mRNAs is universally higher than that of WT LNP-mRNA, which modestly increased antibody titer in neutralization assays of Omicron BA.5, BA.2.12.1 and BA.2. The Delta & BA.2 bivalent LNP-mRNA showed better performance of titer boosting than either monovalent counterparts, which is especially evident in neutralization of Omicron BA.4 or BA.5. Interestingly compared to the neutralizing titers of BA.2 and BA.2.12.1 pseudovirus, BA.2 monovalent but not Delta & BA.2 bivalent booster suffered a significant loss of BA.4/5 neutralizing titer, indicative of broader activity of bivalent booster and strong neutralization evasion of Omicron BA.4 or BA.5 even in the BA.2 mRNA vaccinated individuals. These data provide evaluation of WT, Delta, BA.2 monovalent and bivalent boosters antibody potency against Omicron BA.2, BA.2.12.1 and BA.4/5 subvariants.

show abstract

Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2

Cited by 12 publications

References 53 publications

Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern

Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern

Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron subvariants BA.2, BA.2.12.1 and BA.5

Contact Info

Product

Resources

About