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Antibody Evasion by Omicron Variants BA.4 and BA.5
Omicron has fueled the recent global increase of COVID-19 cases. Omicron’s antibody evasion is one reason for this rise in cases, which Dr. Zhengli Shi, Wuhan Institute of Virology, highlighted in this week’s curator commentary. In their article "Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, & BA.5," Wang, Q., et al. assessed Omicron sublineages BA.2.12.1 and BA.4/5 against a panel of monoclonal antibodies. The authors described BA.4/5 as "substantially" more resistant to neutralization, mainly because of spike protein substitutions at residues L452 and F486. Shi noted that understanding how spike protein substitutions impact neutralization activity are important for informing future vaccines and treatments. Fortunately, Takashita, E., et al. demonstrated the therapeutic antibody bebtelovimab and antivirals remdesivir, molnupiravir and nirmatrelvir retained activity against BA.4 and BA.5 in The New England Journal of Medicine.
Omicron BA.2.75 Substitutions Affect Immune Evasion
Global SARS-CoV-2 genomic sequencing allows scientists to characterize and plan for new variants. The recently emerged Omicron sublineage BA.2.75 carries more spike protein substitutions than BA.4/5. To understand how these changes affect the immune evasion by BA.2.75, Yamasoba, D., et al. assayed pseudoviruses encoding the BA.2.75 spike protein against monoclonal antibodies in their preprint. The authors reported that therapeutic antibodies regdanvimab, sotrovimab and tixagevimab were functional against BA.2.75, though BA.2.75 appears more resistant to bebtelovimab. In another preprint, Cao, Y., et al. found BA.2.75 shows higher immune evasion than BA.4/5 against sera samples from individuals with past Delta infections, with BA.2.75 having a "distinct" antibody evasion profile compared to BA.4/5. The authors suggested this may account for BA.2.75’s growth advantage in India that experienced high rates of infections caused by the Delta variant. These early data on the BA.2.75 Omicron sublineage support continued surveillance, research and characterization of new variants to plan for public health measures.
Boosters Provide Protection Against Omicron
While Omicron variants evade previous immunity, booster doses of COVID-19 vaccines induce neutralizing antibodies to Omicron. In their preprint, Bhiman, J., et al. observed high titers of neutralizing antibodies against Omicron BA.1 and BA.4 after 3 doses of the Novavax COVID-19 vaccine, which the CDC recently recommended for adults in the U.S. Published in Science, Bowen, J., et al. noted increased neutralizing antibodies and antibody breadth against Omicron sublineages in individuals who received a third homologous or heterologous booster dose regardless of vaccine type. In the future, mucosal boosters could be used to bolster protection to variants. Tang, J., et al. in Science Immunology found addition of a mucosal vaccine encoding the spike protein with a primary mRNA vaccination series induced a strong neutralization of the Omicron BA.1.1 variant in a mouse model. In the meantime, vaccinations in conjunction with masking and testing will help slow the summer spike in cases.Lynn Enquist, Ph.D.
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How is the genome of SARS-CoV-2 evolving? What mechanism does the coronavirus use to target human cells? How does the immune system react to SARS-CoV-2?
Will serology provide the ultimate answer? Does the existence of the antibody equal protection due to antibody neutralization? How often should patients be tested?
What are the results of the newest treatment? What drugs are in the pipeline? What are the latest outcomes from clinical trials?
What are the different kinds of vaccines? Do coronaviruses evolve to escape vaccines? What have we learned from work with Ebola virus and SARS vaccines development?
How does a pandemic start? How long will this pandemic last: can data models give us some hints? COVID-19 affects people differently depending on their age, how does this affect transmission? How does social distancing influence transmission rates?
Scientifically speaking, what is a coronavirus? What are the similarities and differences in structure and activities of SARS, MERS and SARS-CoV-2? What is the PK/PD of Remdesivir?
Biweekly Commentary Letter
By Zhengli Shi, Ph.D., senior scientist, Wuhan Institute of Virology, Chinese Academy of Sciences. Shi is a curator of the registry.
"Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5" by Wang, Q., et al., published in Nature on July 5, 2022.
View the Commentary on ASM Connect View Past Commentaries
- Audio Interview: "Understanding the Omicron Variant of SARS-CoV-2" Feb. 24, 2022.
- Audio Interview: "Covid-19 Vaccination and the Omicron Variant" Dec. 30, 2021.
- "How booster shots can help protect you from Omicron" Dec. 17, 2021.
- Audio Interview: "The Omicron Variant of SARS-CoV-2" Dec. 2, 2021.
- Coronapod: "Everything we know about the new COVID variant" Nov. 26, 2021.
- "Are COVID-19 Vaccine Boosters Needed? The Science behind Boosters" Nov. 24, 2021.
- Dr. Vaughn Cooper: "Evolutionary biology of SARS-CoV-2" March 23, 2021 (YouTube 1:01:46).
- COVID-19 Conversations: "Variants and Vaccines" March 17, 2021 (1:27:06).
- Scientific panel discussion on the new variant, 501Y.V2 Jan. 18, 2021 (1:58:28).
- Dr. Vaughn Cooper: "The ongoing evolution of SARS-CoV-2" April 1, 2020 (YouTube11:21).
- Dr. Pamela Bjorkman: "Intro to Viruses, Antivirals, and Vaccines" April 10, 2020 (YouTube 52:57).
- Dr. Scott Page: "Understanding Fatality Rate Models" April 3, 2020 (YouTube 10:12).
- Minute Physics: "How to tell if we’re beating Covid-19" March 27, 2020 (YouTube 7:15).
- 3 Blue 1 Brown "Simulating an Epidemic" March 27, 2020 (YouTube 2:07).
- Dr. Britt Glaunsinger: "Coronaviruses 101, Focus on Molecular Virology" March 25, 2020 (YouTube 1:02:18).
- Dr. Vaughn Cooper: "Evolutionary Biology of Novel Coronavirus SARS-CoV-2" March 24, 2020 (YouTube 11:48).
- Pennings and colleagues: "How does SARS-CoV-2 spread?" March 24, 2020 (Vimeo 8:25).
- Dr. Nick Jewell: "The Exponential Power of Now" March 19, 2020 (YouTube 1:06:00).
- Online Marty: "Disease Spread Simulation" March 18, 2020 (YouTube 2:52).
- Pennings and colleagues: "Coronavirus in numbers" March 11, 2020 (Vimeo 10:18).
- Pennings: "SARS-CoV-2 and phylogenetic trees" March 2, 2020 (Vimeo 14:15).
- University of Pennsylvania: "Coronavirus Outbreak Symposium" April 3, 2020 (YouTube).
- Audio Interview: "Vaccine Efficacy and Boosters in Covid-19" Sept. 23, 2021.
- This Week In Virology: "COVID-19 clinical update #79 with Dr. Daniel Griffin" Sept. 11, 2021.
- Audio Interview: "Another New Covid-19 Vaccine" July 1, 2021.
- Coronapod: "CureVac disappoints in COVID vaccine trial" June 18, 2021 (13:29).
- Coronapod: "The variant blamed for India's catastrophic second wave" May 14, 2021 (8:36).
- Audio Interview: "The Real-World Effectiveness of Covid-19 Vaccination" Feb. 25, 2021.
- Audio Interview: "Covid-19 in South Africa and a New SARS-CoV-2 Variant" Jan. 14, 2021.
- Antimicrobial Agents and Chemotherapy (AAC) Podcast: "Therapeutic approaches for COVID-19: Myths and Facts" May 5, 2020.
- DIY Transcriptomics.
- "COVID-360: A Collaborative Effort to Develop a Multidisciplinary Set of Online Resources for Engaging Teaching on the COVID-19 Pandemic" March 2021 (J. Microbiol. Biol. Educ.).
- "Analysis of a COVID-19 Clinical Trial to Emphasize Experimental Design and Quantitative Reasoning in an Introductory Biology Course" March 2021 (J. Microbiol. Biol. Educ.).
- "Genome Analysis of SARS-CoV-2 Case Study: An Undergraduate Online Learning Activity To Introduce Bioinformatics, BLAST, and the Power of Genome Databases" March 2021 (J. Microbiol. Biol. Educ.).
- "COVID-19, SARS-CoV-2 and the Pandemic" (MIT Free Course).
- Coursera: "Fighting COVID-19 with Epidemiology: A Johns Hopkins Teach-Out" (Free Course).
- "COVID vaccine immunity is waning — how much does that matter?" Sept. 17, 2021.
- "Evolution of the COVID-19 vaccine development landscape" Sept. 4, 2021.
- "Not just antibodies: B cells and T cells mediate immunity to COVID-19" Aug. 24, 2021.
- "How the coronavirus infects cells — and why Delta is so dangerous" July 28, 2021.
- "A correlate of protection for SARS-CoV-2 vaccines is urgently needed" July 8, 2021.
- "How Immunity Generated from COVID-19 Vaccines Differs from an Infection" June 22, 2021.
- "Antibody (Serology) Tests for COVID-19: a Case Study" May 12, 2021.
- "What scientists know about new, fast-spreading coronavirus variants" May 24, 2021.
- "Pfizer COVID vaccine protects against worrying coronavirus variants" May 6, 2021.
- "One million coronavirus sequences: popular genome site hits mega milestone" April 23, 2021.
- "Pandemic Response Catalyst Conversations: Validating & Sharing Scientific Information" Oct. 13, 2020.
- Atul Gawande: "Amid the Coronavirus Crisis, a Regimen for Re-entry" May 13, 2020.
- Dougan and Holt: “How to make a new COVID-19 vaccine starting from scratch” April 9, 2020.