Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques

Deng, Wei; Lv, Qi; Li, Fengdi; Liu, Jiangning; Song, Zhiqi; Qi, Feifei; Wang, Qiang; Yü, Ping; Liu, Mingya; Zhou, Shasha; Zhang, Yaqing; Gao, Hong; Wang, Nan; Jia, Zhimin; Gao, Kai; Liu, Jiayi; Xiao, Cheng; Shang, Haiquan; Wang, Xiangxi; Bao, Linlin; Qin, Chuan

doi:10.1038/s41392-022-00979-z

Cited by 17 publications

(13 citation statements)

References 32 publications

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“…Antigenic distance among different SARS-CoV-2 variants could explain how the efficacy of vaccines could be influenced by the difference or relatedness of prior vaccinations. This study using sequential immunization regimen supports the rationale that boosting Omicron-based vaccines following previous immunizations with the wild strain-based vaccine would selectively induce the immune responses cross-reactive with both the wild strain and Omicron 41 – 43 . Given that the respiratory tract is the most important site for viral entry, transmission, and spread, we compared the performance of different administration routes including intraperitoneal, intranasal and aerosol inhalation.…”

Section: Discussionsupporting

confidence: 67%

Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5

et al. 2023

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SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1–BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.

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Section: Discussionsupporting

confidence: 67%

Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5

et al. 2023

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“…These results are consistent with human serum data obtained after immunization with bivalent mRNA vaccines targeting B.1.351 16,17 or BA.1 14,18 . Increases in neutralizing antibody breadth with bivalent vaccine formulations or boosters also have been reported in the context of inactivated 25,26 and spike protein-based [27][28][29] SARS-CoV-2 vaccine candidates.…”

Section: Discussionmentioning

confidence: 73%

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

Scheaffer

Lee

Whitener

et al. 2022

Preprint

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The emergence of SARS-CoV-2 variants in the Omicron lineage with large number of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.

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“…Omicron displays a reduced pathogenic phenotype in animal models. Virus replication in the lower respiratory tract is reduced both in rodents [ 43 , 44 ] and non-human primates [ 45 , 46 ]. Omicron also displays a reduced transmission efficiency compared to Lineage A, Alpha, and Delta in hamsters.…”

Section: Discussionmentioning

confidence: 99%

Infection- or vaccine mediated immunity reduces SARS-CoV-2 transmission, but increases competitiveness of Omicron in hamsters

Port

Yinda

Riopelle

et al. 2022

Preprint

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Omicron has demonstrated a competitive advantage over Delta in vaccinated people. To understand this, we designed a transmission chain experiment using naive, intranasally (IN) or intramuscularly (IM) vaccinated, and previously infected (PI) hamsters. Vaccination and previous infection protected animals from disease and virus replication after Delta and Omicron dual challenge. A gradient in transmission blockage was observed: IM vaccination displayed moderate transmission blockage potential over three airborne chains (approx. 70%), whereas, IN vaccination and PI blocked airborne transmission in >90%. In naive hamsters, Delta completely outcompeted Omicron within and between hosts after dual infection in onward transmission. Although Delta also outcompeted Omicron in the vaccinated and PI transmission chains, an increase in Omicron competitiveness was observed in these groups. This correlated with the increase in the strength of the humoral response against Delta, with the strongest response seen in PI animals. These data highlight the continuous need to assess the emergence and spread of novel variants in populations with pre-existing immunity and address the additional evolutionary pressure this may exert on the virus.

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Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques

Cited by 17 publications

References 32 publications

Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5

Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

Infection- or vaccine mediated immunity reduces SARS-CoV-2 transmission, but increases competitiveness of Omicron in hamsters

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