Current COVID-19 Vaccines Have Drawbacks
COVID-19 vaccine development so far has mainly focused on stimulating the production of antibodies against a viral protein known as Spike. Spike is present on the surface of SARS-CoV-2, and besides being critical for the virus’ ability to enter cells, it also gives coronavirus its crown-like appearance when viewed under a microscope.
Given its location and function, vaccine developers rationalised that a vaccine that blocks Spike, through the development of anti-Spike antibodies, would be an effective strategy to prevent infection by SARS-CoV-2. Unlike T cells that only spring into action once infection has set in, antibodies, if present in high enough numbers, can block infection entirely by binding to the virus and preventing it from entering cells.
However, despite current efficacy rates above 90 % for most of the approved COVID-19 vaccines, antibodies wane over time, and experts are already discussing the need for boosters and annual revaccination to keep yearly infection rates under control.
T Cell-Inducing Vaccines Are Key to Long-Term Immunity
Concerns about antibody-driven COVID vaccines have prompted scientists to look at other parts of the immune system that might provide longer lasting and broader immune responses, and T cells are in the spotlight.
It’s well known as proper CD8 and CD4 T cell activation are critical for clearance of viruses such as influenza and human immunodeficiency virus (HIV), and multiple studies indicate that this is also the case for SARS-CoV-2. Furthermore, while T cells can’t prevent infection, they are crucial for clearing established infections and they may be the difference between a mild and a severe infection (2).
In one study conducted last year, 70 % of recovered COVID-19 patients were found to have SARS-CoV-2-specific CD8 T cell responses and all patients in the same study had CD4 T cell responses (3). The importance of the T cells is further highlighted by studies revealing that antibody responses to SARS-CoV-2 are short-lived and may even cause or aggravate virus-associated lung pathology (4, 5).
With respect to coronavirus variants, T cells have the advantage of being able to target viral epitopes derived from any SARS-CoV-2 protein, unlike neutralising antibodies that can only bind surface proteins from circulating virus particles. As a result, it is likely more difficult for variants to escape T cell immunity than neutralising antibody responses.
T Cell Responses to COVID-19 Are Broad and Robust Against Variants
Recent research led by Alessandro Sette at the La Jolla Institute for Immunology in California found that people infected with SARS-CoV-2 generally produce T cells that can target at least 15-20 SARS-CoV-2 epitopes from several viral proteins (6). Such a broad immune response would be more difficult for a coronavirus variant to escape than an antibody-based response based on Spike epitopes alone.
Preliminary findings from the UK further support the potential of T cell-inducing vaccines to control novel variants. Here, researchers found that the UK and South African variants displayed some resistance to antibodies from previously infected individuals and to a lesser extent from vaccinated individuals. However, the impact of these variants on T cell responses from previously infected individuals was much less pronounced, in other words the T cell responses could protect against future infections with variants (7).
Study results published late last year also suggest that while antibody responses following SARS-CoV-2 infection might not be long-lasting, immune memory might be achieved through virus-specific memory T cells (8).
Immunitrack Is Ready For Next-Generation COVID-19 Vaccines
The ability to screen the entire SARS-CoV-2 proteome for T cell-inducing epitopes is crucial to developing a vaccine that can stimulate broad T cell immune responses. Immunitrack’s high-throughput epitope screening technology has the capacity to do this against a diverse range of human leukocyte antigens (HLAs) from all major human populations.
Immunitrack’s expert competences in predicting and analysing T cell responses positions it as a key partner for T-cell inducing vaccine development and it is already working with an industrial partner to develop a population-specific COVID-19 vaccine. Tailor-making a vaccine to a specific population is a unique approach to vaccine development, and Immunitrack can do this because it has access to a broad HLA library and unmatched expertise in working with many diverse HLA genes.
Given the importance of T cell responses in clearing viral infections, T cell-inducing vaccines have potential in controlling diseases beyond COVID-19, and Immunitrack is already involved in a number of projects in this area, e.g., a T cell- and antibody-inducing vaccine for Zika virus in collaboration with the University of Liverpool, UK.
