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

Fang, Zhenhao; Peng, Lei; Lucas, Carolina; Lin, Qianqian; Zhou, Liqun; Yang, Luojia; Feng, Yanzhi; Ren, Ping; Renauer, Paul; Monteiro, Valter Silva; Hahn, Anne M.; Park, Jonathan J.; Zhou, Xiaoyu; Billig, Kendall; Breban, Mallery I.; Castaldi, Christopher; Chaguza, Chrispin; Chen, Nicholas; Ferguson, David; Kerantzas, Nicholas; Koch, Tobias R.; Kumar, Bony De; Landry, Marie L.; Peaper, David R.; Pham, Kien; Schulz, Wade; Tikhonova, Irina; Vogels, Chantal B.F.; Grubaugh, Nathan D.; Wilen, Craig B.; Chen, Sidi

doi:10.1038/s41421-022-00435-w

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…S4 , S8a ). These data highlight the advantage of variant-adapted boosters administration, which is consistent with our previous reports 8 – 10 . Interestingly, compared to the neutralizing titers against BA.2 and BA.2.12.1, BA.2 monovalent but not Delta & BA.2 bivalent booster suffered a loss of BA.4/5 pseudovirus and authentic virus neutralizing titers (Supplementary Fig.…”

supporting

confidence: 92%

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5

et al. 2022

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supporting

confidence: 92%

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5

et al. 2022

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“… 13 , 14 The fourth COVID‐19 wave of South Africa was associated with BA.1 and BA.2. 15 , 16 , 17 In South Africa from April 2022, BA.4 and BA.5 have rapidly replaced BA.2 and initiated the fifth COVID‐19 wave, accounted for more than 50% of sequenced cases. 18 , 19 , 20 The current review article aims to analyse the characteristics of key spike mutations, epidemic characteristics, humoral and cellular immunity, and vaccine effectiveness of five Omicron lineages, especially Omicron BA.2, BA.4, and BA.5.…”

Section: Introductionmentioning

confidence: 99%

“…Since then, BA.2 has increased in many countries, and is more transmissible and possesses a selective advantage over BA.1 13,14 . The fourth COVID‐19 wave of South Africa was associated with BA.1 and BA.2 15–17 . In South Africa from April 2022, BA.4 and BA.5 have rapidly replaced BA.2 and initiated the fifth COVID‐19 wave, accounted for more than 50% of sequenced cases 18–20 .…”

Section: Introductionmentioning

confidence: 99%

The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape, and vaccine effectivity

Zhou

Zhi

Teng

2022

Journal of Medical Virology

100

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As of November 2021, several SARS‐CoV‐2 variants appeared and became dominant epidemic strains in many countries, including five variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron defined by the World Health Organization during the COVID‐19 pandemic. As of August 2022, Omicron is classified into five main lineages, BA.1, BA.2, BA.3, BA.4, BA.5 and some sublineages (BA.1.1, BA.2.12.1, BA.2.11, BA.2.75, BA.4.6) ( https://www.gisaid.org/ ). Compared to the previous VOCs (Alpha, Beta, Gamma, and Delta), all the Omicron lineages have the most highly mutations in the spike protein, and with 50 mutations accumulated throughout the genome. Early data indicated that Omicron BA.2 sublineage had higher infectivity and more immune escape than the early wild‐type (WT) strain, the previous VOCs, and BA.1. Recently, global surveillance data suggest a higher transmissibility of BA.4/BA.5 than BA.1, BA.1.1 and BA.2, and BA.4/BA.5 is becoming dominant strain in many countries globally.

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“…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 . WT, Delta and BA.2 spike plasmids were linearized by restriction enzymes and transcribed to mRNA by in vitro T7 RNA polymerase (NEB, Cat # E2060S) as previously described 10 .…”

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

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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.

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

Cited by 6 publications

References 10 publications

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5

The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape, and vaccine effectivity

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

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