In the midst of the COVID-19 pandemic, researchers have been working tirelessly to develop effective treatments against the SARS-CoV-2 virus. One potential solution that has garnered significant attention is the use of broadly neutralizing antibodies (bnAbs) against the virus. Recently, a team of researchers reported the successful generation of bnAbs against SARS-CoV-2 and related sarbecoviruses through immunization.
First, let's break down what we mean by "broadly neutralizing antibodies." Antibodies are proteins produced by the immune system that can recognize and bind to specific molecules, called antigens, on the surface of pathogens like viruses. By binding to these antigens, antibodies can prevent the virus from infecting cells or help to flag infected cells for destruction by other immune cells. However, because viruses can mutate rapidly, they can also evolve new antigens that are not recognized by existing antibodies, making it difficult to develop effective treatments.
Broadly neutralizing antibodies, as the name suggests, are antibodies that can recognize and bind to a wide range of antigen variants. This makes them particularly valuable in the fight against rapidly evolving viruses like SARS-CoV-2.
The team of researchers, led by scientists at the University of Washington, used a strategy called "germline-targeting immunization" to generate bnAbs against sarbecoviruses. Germline targeting involves using a vaccine to stimulate the immune system to produce antibodies that are similar to the precursor antibodies found in the germline cells that give rise to all other immune cells. These precursor antibodies have the potential to develop into bnAbs, so by targeting them, researchers hope to generate a more effective immune response.
The researchers used a vaccine candidate that contained stabilized spike proteins from SARS-CoV-2 and related sarbecoviruses. They immunized mice with the vaccine and then used a process called "single B cell sorting" to identify the cells that produced the most promising bnAbs. They then isolated the genetic code for these bnAbs and used it to create synthetic versions of the antibodies, which were then tested in vitro against a range of sarbecoviruses.
The results were promising: the team identified several bnAbs that were able to neutralize a wide range of sarbecoviruses, including SARS-CoV-2, SARS-CoV-1 (the virus that caused the 2002-2003 SARS outbreak), and bat sarbecoviruses. The researchers note that further studies will be needed to assess the safety and efficacy of these bnAbs in humans, but they believe that the germline-targeting immunization strategy could be a promising approach for generating effective treatments against emerging viral diseases.
Overall, the generation of bnAbs against sarbecoviruses represents an important advance in the ongoing efforts to combat COVID-19 and related viruses. By harnessing the power of the immune system to produce highly effective antibodies, researchers may be able to develop more targeted and durable treatments against these rapidly evolving pathogens.
Commonly Asked Questions:
What is vaccine neutralizing antibody?
What is the target of neutralizing antibodies against influenza virus?
What are broadly neutralizing antibodies for Covid 19?
What are non-neutralizing antibody responses?
A vaccine neutralizing antibody is an antibody that specifically targets and neutralizes a pathogen, such as a virus or bacterium, preventing it from infecting cells in the body. These antibodies are generated by the immune system in response to vaccination or natural infection.
The target of neutralizing antibodies against influenza virus is the viral surface protein hemagglutinin (HA), which is responsible for allowing the virus to enter host cells. Neutralizing antibodies bind to the HA protein and prevent it from attaching to host cells, thereby blocking viral entry and replication.
Broadly neutralizing antibodies for COVID-19 are a class of antibodies that can recognize and neutralize multiple strains of the SARS-CoV-2 virus, including variants of concern. These antibodies are highly effective in preventing viral entry and replication and have shown promise as potential therapeutics for COVID-19.
Non-neutralizing antibody responses are immune responses that generate antibodies that do not directly neutralize a pathogen, but instead, bind to it and facilitate its clearance by other immune cells. Non-neutralizing antibodies can also have other functions, such as signaling to other immune cells or activating complement pathways. While non-neutralizing antibodies may not prevent infection on their own, they can still contribute to overall protection against a pathogen.
References:
Schmidt F, Weisblum Y, Rutkowska M, et al. Broadly neutralizing antibody against SARS-CoV-2 and emerging variants. Nature. 2021; 592: 616-621. doi: 10.1038/s41586-021-03396-3.
Wu NC, Yuan M, Bangaru S, et al. An alternative binding mode of IGHV3-53 antibodies to the SARS-CoV-2 receptor binding domain. Cell Rep. 2021; 34(13): 108946. doi: 10.1016/j.celrep.2021.108946.
Baum A, Fulton BO, Wloga E, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science. 2020 Aug 21;369(6506):1014-1018. doi: 10.1126/science.abd0831. Epub 2020 Jul 15. PMID: 32669339; PMCID: PMC7360745.
Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021 Feb 11;384(6):497-499. doi: 10.1056/NEJMc2033369. Epub 2020 Oct 28. PMID: 33113295; PMCID: PMC7646211.
Liu L, Wang P, Nair MS, et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020 Oct;584(7821):450-456. doi: 10.1038/s41586-020-2571-7. Epub 2020 Jul 22. PMID: 32703872; PMCID: PMC7852113.
McCallum M, De Marco A, Lempp FA, et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell. 2021 Jan 7;184(1):233-245.e16. doi: 10.1016/j.cell.2020.12.028. Epub 2020 Dec 23. PMID: 3330698; PMCID: PMC7768697.
Pinto D, Park YJ, Beltramello M, et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020 Aug;583(7815):290-295. doi: 10.1038/s41586-020-2349-y. Epub 2020 May 18. PMID: 32422645; PMCID: PMC7288833.
Starr TN, Greaney AJ, Hilton SK, et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell. 2020 Sep 3;182(5):1295-1310.e20. doi: 10.1016/j.cell.2020.08.012. Epub 2020 Aug 6. PMID: 32877694; PMCID: PMC7411997.
Wang P, Casner RG, Nair MS, et al. Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell Host Microbe. 2021 Apr 14;29(4):747-751.e4. doi: 10.1016/j.chom.2021.03.007. Epub 2021 Mar 24. PMID: 33765437; PMCID: PMC7991442.