The road to an improved coronavirus vaccine is complex. Yet, it is one of the most pressing challenges in the effort to protect against COVID-19. This blog describes how single-cell RNA sequencing helps map out the small steps toward vaccine improvement.
The ongoing COVID-19 pandemic is far from an end. Vaccines are at the basis of the fight against COVID-19, and although current vaccines are already very effective, the scientific world is taking on the challenge to improve them further.
One of the main goals of SARS-CoV-2 vaccination is to create neutralizing antibodies and memory B cells that protect against future infection. So, understanding the human B cell response to SARS-CoV-2 could accelerate vaccine redesign.
Single-cell RNA sequencing helps identify B cells in the SARS-CoV-2 response
Single-cell RNA sequencing can be used to explore adaptive and innate immune cell diversity, for example B cell diversity. It can characterize the immune response to infection or treatment on single-cell resolution.
In this study, researchers from the Amsterdam UMC and The Scripps Research Institute of La Jolla, USA, investigated the B cell population in people not previously exposed to the virus or vaccine. Even when you’re unexposed to the coronavirus, some of your B cell receptors and antibodies already recognize the spike protein. The researchers could isolate those particular B cells using stained coronavirus spike proteins. Then, they used flow cytometry and single-cell RNA sequencing to describe the spike protein-reactive B cell repertoire.
10x Genomics reveals which B cell receptors react with the spike protein
The researchers used the single-cell RNA sequencing platform 10x Genomics‘ Next GEM technology for single-cell immune profiling. This technique allows for high throughput and so identifies even rare subpopulations. In this case, the researchers studied 8000 live B cells on a single-cell resolution. They combined 10x Genomics with the Feature Barcoding technique, allowing them to profile the B cell receptors. This way, the researchers could make a reliable analysis of the compartment to which the B cells belonged (naïve or memory) ánd which B cell receptors are present in the population that binds to the SARS-CoV-2 spike protein.
The results came back with a fundamental find that could guide vaccine optimization.
In unexposed individuals, the SARS-CoV-2 spike protein mainly elicits the response of one type of antibody. It is derived from the B cell receptor IGHV1-69/IGKV3-11, so named because of the heavy chain and light chain that make up the antibody. This B cell receptor is overly present in the naive B cell repertoire. Moreover, some unexposed people already have memory B cells that respond to SARS-CoV-2 with this receptor too.
The antibody that is derived from IGHV1-69/IGKV3-11 is non-neutralizing. That’s important. Non-neutralizing antibodies help signal to the immune system that there’s viral danger, and they can also help mediate the response and prevent dangerous auto-immune reactions. But they cannot block viruses from spreading, the way neutralizing antibodies can. It would mean that, in the vaccine, an IGHV1-69/IGKV3-11 B cell response might best be replaced by a response that favors neutralizing antibodies.
Stability of the spike protein affects the B cell response
The researchers revealed that the non-neutralizing antibody mainly targets a part of the spike protein that is usually unexposed unless the spike protein becomes unstable. If the vaccine could prevent instability or replace the spike protein with a more stable version, it could create a more neutralizing immune reaction. Indeed, some of the approved vaccines already contain a more stable S-2P spike protein variant.
Does this improve the SARS-CoV-2 vaccine? It is not entirely sure. Non-neutralizing antibodies do have an effect in the immune response. They may still play a role in clearing SARS-CoV-2 from the body. And they may also be important in preventing long-term effects from infection or vaccination by their mediating powers on the immune system.
The next step on the road to improved vaccines
Is the vaccine improved if the IGHV1-69/IGKV3-11 response it elicits is decreased? A next step on the road toward a better vaccine would be to tackle this question. In the intricate struggle to improve the SARS-CoV-2 vaccine, it’s great to have a roadmap like that.
Improvement of a SARS-CoV-2 vaccine isn’t the only way Single Cell Discoveries hopes to aid the anti-COVID-19 effort. For example, we’re helping develop nasal airway epithelial cell cultures for high-throughput drug development. In the past, we also contributed to an organoid-derived bronchioalveolar model to study alveolar response to SARS-CoV-2 infection by providing the data that confirmed the model’s likeness to real tissue. Another collaborative study showed that SARS-CoV-2 can infect gut organoids for the first time, to which our data also contributed. We hope to support more projects in the future.
Read the full article here: