Unleashing the Defenders: How Vaccines Train Your Body to Fight a Diverse SARS-CoV Family
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.
The emergence of SARS-CoV-2 and its variants has highlighted the need for vaccines that offer broad protection against not just one specific strain, but the entire family of Sarbecoviruses – viruses like SARS-CoV and bat coronaviruses with pandemic potential. So, how do we train our immune system to create these broadly neutralizing antibodies (bnAbs)?
Here's a breakdown of the science behind these powerful immune warriors:
The Training Ground: Introducing the Antigen
Vaccines work by introducing a weakened or inactivated form of the virus, or a specific viral antigen (a protein or sugar molecule recognized by the immune system) to the body. This antigen acts like a training dummy for your immune system.
B-Cells: The Antibody Factories
When your immune system encounters this antigen, a special type of white blood cell called a B-cell springs into action. These B-cells are like factories, each with the potential to produce a unique antibody specifically designed to attack the antigen.
The Selection Process: Finding the Best Fit
Millions of B-cells are activated, each producing different antibodies. Here's where the magic happens! The body then puts these antibodies through a rigorous selection process. Only the antibodies that bind most effectively to the viral antigen survive. These "winning" B-cells are then stimulated to multiply and produce large quantities of these highly effective antibodies, – our broadly neutralizing antibodies!
The Power of bnAbs: Recognizing Similarities
These bnAbs are special because they target conserved regions – parts of the virus that are similar across different strains within the Sarbecovirus family. By binding to these conserved regions, bnAbs can effectively neutralize a wide range of related viruses, not just the specific strain used in the vaccine.
Vaccines in Action: Different Strategies
There are different approaches to vaccine development that can promote bnAb production:
Whole Virus Vaccines: These introduce a weakened or inactivated whole virus, exposing the immune system to a variety of antigens, potentially leading to the creation of bnAbs.
Subunit Vaccines: These vaccines focus on specific viral antigens known to be targets for bnAbs.
Viral Vector Vaccines: These use a harmless virus as a carrier to deliver viral genetic material that instructs cells to produce specific antigens, potentially promoting bnAb development.
The Future of Broader Protection
Research into bnAbs is ongoing, with scientists working to develop vaccines that specifically target these conserved regions and elicit a strong bnAb response. This holds promise for creating vaccines that offer broader protection against not just current Sarbecoviruses, but also potential future threats.
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.
Barnes CO, Jette CA, Abernathy ME, et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020 Oct;588(7839):682-687. doi: 10.1038/s41586-020-2852-1. PMID: 32967005; PMCID: PMC7674060.
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.
What did you think of this article?
We value your feedback and would love to hear your thoughts on this article.
Write to: hello [at] watchdoq [dot] com with questions or comments.
Additional Resources