Related references
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Wanwisa Dejnirattisai et al.
Summary: On November 24, 2021, the sequence of a new SARS-CoV-2 variant, Omicron-B.1.1.529, was announced. Compared to previous variants, Omicron has a higher number of mutations in the Spike (S) protein. Serum neutralization of Omicron by individuals vaccinated or previously infected with Alpha, Beta, Gamma, or Delta variants is significantly reduced or ineffective. Third vaccine doses can boost neutralization titers against Omicron, and high titers are observed in both vaccinated individuals and those infected with the Delta variant. Most potent monoclonal antibodies and antibodies under development are unable to effectively neutralize Omicron due to mutations in its Spike protein. Omicron has structural changes compared to earlier viruses and utilizes mutations that enhance its binding to ACE2, allowing for immune escape. This results in a large number of mutations in the ACE2 binding site and a rebalancing of receptor affinity similar to earlier pandemic viruses.
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Summary: This study investigated several variants of SARS-CoV-2 and found that the Beta variant has the largest antigenic difference compared to other variants, such as Delta, and is poorly neutralized by serum from early pandemic and Delta viruses. The study also revealed that certain antibodies can recognize conserved neutralizing epitopes, while others target specific mutated residues in the Beta variant.
CELL HOST & MICROBE
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Yunlong Cao et al.
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Lihong Liu et al.
Summary: The B.1.1.529/Omicron variant of SARS-CoV-2, initially detected in southern Africa, has rapidly spread globally and is expected to become dominant due to its enhanced transmissibility in the coming weeks. This variant poses a threat to the efficacy of current COVID-19 vaccines and antibody therapies due to its significant antibody resistance. Even individuals who have received vaccines and booster doses may have reduced neutralizing activity against B.1.1.529.
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Summary: SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies. The antibodies elicited by infection with B.1.351 variant are more focused on the class 3 epitope, which is mutated in the Delta variant. Prior infection and vaccination histories may partially determine individuals' susceptibilities to viral mutants in new variants.
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John P. Evans et al.
Summary: Recent reports show that SARS-CoV-2 Omicron variant sub-lineages BA.1, BA.1.1, and BA.2 have raised concerns about their ability to escape vaccine-induced and infection-induced immunity. A study finds that all Omicron sub-lineages, especially BA.1 and BA.1.1, exhibit significant immune escape, but this can be largely overcome by mRNA vaccine booster doses. The findings highlight the importance of booster vaccine doses for protection against all Omicron variants and provide insights into the immunity from natural infection against Omicron sub-lineages.
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Kentaro Tohma et al.
Summary: RNA viruses have the ability to mutate and evade immunity. Antibody responses play a crucial role in viral immunity, but antigenic sites are subject to strong diversifying pressure. Using norovirus as a model, this study investigates the mechanisms of antigenic diversification in non-enveloped, rapidly evolving RNA viruses. The findings reveal that single neutralizing monoclonal antibodies (mAbs) target multiple antigenic sites of GII.4 norovirus. Interactions between multiple epitopes on the viral capsid surface result in a wide range of mAb-binding profiles and differences in immunodominance hierarchy between distantly related GII.4 variants. Time-ordered mutant viruses demonstrate a progressive change in antibody immunodominance along with point mutations during norovirus evolution. Thus, in addition to point mutations, switches in immunodominance could contribute to immune escape in RNA viruses.
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Jasmin Quandt et al.
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Summary: Analyzing vaccinated individuals infected with Omicron/BA.1, this study reveals that vaccination activates memory B cells, leading to specific antibody responses against breakthrough infections. Moreover, the hierarchy of B cell immunodominance was found to shift towards the variable receptor binding domain, indicating the role of preexisting immunity in shaping the immune response against heterologous SARS-CoV-2 variants.
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Annika Roessler et al.
Summary: Studies have shown that the omicron variant of SARS-CoV-2 is an immune escape variant. However, the BA.2 and BA.5 sub-variants of omicron have become dominant in many countries and replaced the BA.1 variant. Our analysis focused on whether BA.2 and BA.5 show further immune escape compared to BA.1. We found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and BA.1.
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Summary: Large-scale vaccination campaigns have been effective in preventing hospitalizations and deaths from COVID-19, but the emergence of SARS-CoV-2 variants that can evade immunity poses challenges to vaccine effectiveness. This study found that certain variants, particularly Omicron BA.1 and BA.2, were highly resistant to neutralization by antibodies produced in response to other variants. This suggests that vaccine updates may be necessary to ensure continued protection against evolving strains.
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Young-Jun Park et al.
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Summary: The expression level of ACE2 in target cells is an important factor affecting the neutralization activity of antibodies. Higher ACE2 expression emphasizes the role of RBD-directed antibodies, while lower ACE2 expression allows antibodies targeting regions outside the RBD to contribute to neutralization.
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Elizabeth M. Anderson et al.
Summary: The study found that SARS-CoV-2 infections and mRNA vaccinations elicit fundamentally different antibody responses. Infection and initial vaccination produce S1 and S2 reactive antibodies, while secondary vaccination mainly enhances S1 antibodies. The research also revealed that infections generate a large proportion of antibodies with efficient binding to the spike protein of common seasonal human coronaviruses but poor binding to the spike protein of SARS-CoV-2, whereas vaccination boosts antibodies that react to the spike protein of common seasonal human coronaviruses and cross-react more efficiently to the spike protein of SARS-CoV-2.
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Summary: This study analyzed the antibody response after Omicron/BA.1 infection in mRNA-vaccinated donors. The findings highlighted strong immune responses and recognition of SARS-CoV-2 variant strains, emphasizing the early role of vaccine-induced memory B cells.
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Kara L. Lynch et al.
Summary: Understanding the kinetics and magnitude of the host antibody response to SARS-CoV-2 is essential for understanding the pathogenesis of COVID-19 and identifying potential therapeutic targets. Research showed that IgM and IgG responses were significantly higher in patients with severe disease compared to those with mild disease, which may have implications for seroprevalence studies, therapeutics, and vaccine development strategies.
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Summary: The D614G mutation in the spike protein of SARS-CoV-2 is not expected to hinder current vaccine development, as viruses with the G614 spike are more susceptible to neutralization, indicating that the mutation may not affect vaccine efficacy.
CELL HOST & MICROBE
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Piyada Supasa et al.
Summary: Research on the UK-dominant variant B.1.1.7 shows that it is harder to neutralize than the parental virus, but widespread escape from antibodies or monoclonal antibodies has not been observed yet.
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Daming Zhou et al.
Summary: The race to develop vaccines against SARS-CoV-2 variants, such as B.1.1.7, B.1.351, and P.1, is ongoing as these variants have mutations in the spike protein, potentially leading to immune escape. A structure-function analysis of B.1.351 revealed tighter ACE2 binding and widespread evasion from monoclonal antibody neutralization, particularly driven by the E484K mutation.
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Xiaoying Shen et al.
Summary: Current COVID-19 vaccines target the ancestral SARS-CoV-2 spike, but the emerging B.1.1.7 variant with multiple spike mutations may impact some antibody therapies while posing no major concerns for vaccine efficacy or increased risk of reinfection.
CELL HOST & MICROBE
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Carolina Lucas et al.
Summary: This study found that individuals previously infected with the virus had higher antibody titres post-vaccination compared to those who were uninfected, but both groups reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. Comprehensive analysis of 16 locally circulating SARS-CoV-2 variants revealed varying degrees of reduction in neutralization capacity associated with specific mutations in the spike gene, suggesting vaccine boosters as a relevant future strategy to counteract the impact of emerging variants on antibody neutralizing activity.
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Pengfei Wang et al.
Summary: The COVID-19 pandemic has had global repercussions, with promising vaccines and monoclonal antibody therapies. However, newly detected variants of SARS-CoV-2 present challenges to these treatment options.
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Summary: Infection with dengue viruses leads to protective antibodies, but the viruses can also use heterotypic antibodies to infect immune cells, worsening the disease. The antigenic dynamics of DENV serotypes in Thailand evolved over a 20-year period, with periods of increased similarity between serotypes correlating with changes in epidemic magnitude.
Correction
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Review
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Katharina Roltgen et al.
Summary: Human immune responses to SARS-CoV-2 have made significant progress in understanding the nature of antibody responses and their role in protecting against infection or modulating the severity of COVID-19, aiding in the development of effective vaccines. However, important questions remain unanswered regarding the duration and effectiveness of antibody responses, immunity differences between infection and vaccination, cellular basis for serological findings, and the potential impact of viral variants on current immunity.
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Summary: Despite challenges posed by COVID-19 variants, convalescent individuals receiving mRNA vaccines exhibit robust and long-lasting immune responses against circulating SARS-CoV-2 variants, providing hope for effective control of the pandemic.
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