Breakthrough Infections of E484K-Harboring SARS-CoV-2 Delta Variant, Lombardy, Italy

Baj, Andreina; Novazzi, Federica; Pasciuta, Renée; Genoni, Angelo; Ferrante, Francesca Drago; Valli, Marilena; Partenope, Michele; Tripiciano, Rosalia; Ciserchia, Andrea; Catanoso, Giuseppe; Focosi, Daniele; Maggi, Fabrizio

doi:10.3201/eid2712.211792

Cited by 21 publications

(20 citation statements)

References 3 publications

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“… 63 , 84 − 86 However, breakthrough infections, particularly with variant strains, have been reported even in the presence of detectable and high-level NtAbs. 55 , 57 , 60 , 63 , 87 Anamnestic responses in fully immunized NHPs have been characterized previously with homologous and B.1.351 variant challenge and agree with our observations that viral challenge boosts functional antibody levels. Our analysis shows that viral challenge with a heterologous strain rapidly boosts not only homologous and challenge strain-specific NtAbs but also NtAbs against the unencountered variants, B.1.351 and B.1.617, underpinning the broad-spectrum potential of subunit protein vaccines.…”

Section: Discussionsupporting

confidence: 92%

A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant

Wong

Lieberman

et al. 2022

ACS Infect. Dis.

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FDA-approved and emergency use-authorized vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease; however, information on their long-term efficacy and protective breadth against severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) is currently scarce. Here, we describe the durability and broad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], and B.1.617 [Delta]) for at least three months after the final boost. Protective efficacy and postexposure immunity were evaluated using a heterologous P.1 challenge nearly three months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Postchallenge IgG concentrations were restored to peak immunity levels, and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (nonvaccinated but challenged) macaques, suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide protective immunity against circulating VOCs for at least three months.

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Section: Discussionsupporting

confidence: 92%

A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant

Wong

Lieberman

et al. 2022

ACS Infect. Dis.

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“…This amino acid substitution in the receptor-binding domain, occurring in other VOC such as Beta and Gamma, is associated with reduced sensitivity to monoclonal antibodies, convalescent antisera from early pandemic wave infections, and vaccine elicited anti-sera [ 6 , 16 , 17 ]. While Delta variants bearing the E484K mutation occur mostly sporadically [ 8 ], it has now occurred in Delta sub-lineages with sustained clusters according to recent reports from the UK [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, from the last week of October 2021, the percentage of AY.4.2 increased again from 0.5% to 4% by 21 November 2021. In addition to Beta and Gamma, the E484K mutation has emerged in several different lineages, including Delta [ 8 , 15 ]. Between 29 August and 15 November 2021, 56 cases of Delta strains with the E484K mutation have been identified in Denmark.…”

Section: Prevalence Of Ay42 and B16172 With E484k In Denmarkmentioning

confidence: 99%

“…The Delta sub-lineage AY.4.2 has spread globally, evidenced by over 48,000 sequences uploaded onto GISAID from 42 countries [ 3 ] and frequencies above 1% observed in Romania and Poland [ 4 ] as at 23 November 2021. A Delta strain bearing a known neutralisation-resistant mutation, E484K [ 5 , 6 ], has also established small clusters in the UK [ 7 ] and contributed to breakthrough infections in Italy [ 8 ]. Here, we investigate the sensitivity of the Delta sub-lineage AY.4.2 and Delta lineage B.1.617 with the E484K mutation (+ E484K) to neutralisation by SARS-CoV-2 Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer, Mainz, Germany/New York, United States (US)) vaccine-induced anti-sera.…”

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confidence: 99%

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Neutralisation of the SARS-CoV-2 Delta variant sub-lineages AY.4.2 and B.1.617.2 with the mutation E484K by Comirnaty (BNT162b2 mRNA) vaccine-elicited sera, Denmark, 1 to 26 November 2021

et al. 2021

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Several factors may account for the recent increased spread of the SARS-CoV-2 Delta sub-lineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. We evaluated the sensitivity of AY.4.2 to neutralisation by sera from 30 Comirnaty (BNT162b2 mRNA) vaccine recipients in Denmark in November 2021. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sub-lineages. Conversely, the less prevalent B.1.617.2 with E484K showed a significant more than 4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.

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“…Up to now, the current epidemic of COVID-19 has become a normalized situation, whereby most countries have been able to keep the number of cases to a low level. However, because of virus mutation [ 4 , 5 ], there are still local outbreaks in some countries and regions [ 6 ]. Especially in large-scale public facilities such as transportation and entertainment venues that are essential for public normal life, local outbreaks are more likely to occur.…”

Section: Introductionmentioning

confidence: 99%

A Network Dynamics Model for the Transmission of COVID-19 in Diamond Princess and a Response to Reopen Large-Scale Public Facilities

Zhu

Wang

et al. 2022

Healthcare

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Background: The current epidemic of COVID-19 has become the new normal. However, the novel coronavirus is constantly mutating. In public transportation or large entertainment venues, it can spread more quickly once an infected person is introduced. This study aims to discuss whether large public facilities can be opened and operated under the current epidemic situation. Methods: The dual Barabási–Albert (DBA) model was used to build a contact network. A dynamics compartmental modeling framework was used to simulate the COVID-19 epidemic with different interventions on the Diamond Princess. Results: The effect of isolation only was minor. Regardless of the transmission rate of the virus, joint interventions can prevent 96.95% (95% CI: 96.70–97.15%) of infections. Compared with evacuating only passengers, evacuating the crew and passengers can avoid about 11.90% (95% CI: 11.83–12.06%) of infections; Conclusions: It is feasible to restore public transportation services and reopen large-scale public facilities if monitoring and testing can be in place. Evacuating all people as soon as possible is the most effective way to contain the outbreak in large-scale public facilities.

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Breakthrough Infections of E484K-Harboring SARS-CoV-2 Delta Variant, Lombardy, Italy

Cited by 21 publications

References 3 publications

A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant

A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant

Neutralisation of the SARS-CoV-2 Delta variant sub-lineages AY.4.2 and B.1.617.2 with the mutation E484K by Comirnaty (BNT162b2 mRNA) vaccine-elicited sera, Denmark, 1 to 26 November 2021

A Network Dynamics Model for the Transmission of COVID-19 in Diamond Princess and a Response to Reopen Large-Scale Public Facilities

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