Part 1 of A Vaccine Journey, about COVID-19 drug development
Rhiannon Jenkinson, PhD

The Hunt for a COVID Vaccine: How Scientists Advanced their Target

Science, innovation, determination and funding drive rapid progress in the discovery of viable candidates. The first in a multi-part series.

Vaccine development typically takes years, even decades. How then could companies deliver COVID-19 vaccines in a matter of months? Can we trust the process? These two questions have been dominating the airwaves ever since the first three candidates in the pipeline were authorized by regulators, a mere 11 months after SARS-CoV-2 emerged in China. We hope Eureka’s six-part series, The Vaccine Journey, on how vaccines are developed—from discovery through manufacturing—help answer some of these questions and reassures readers that vaccines are generally very safe. Our first installment, from Rhiannon Jenkinson, PhD, explains key reasons why scientists were able to discover their COVID-19 vaccine candidates in record time.

Identifying a vaccine candidate that might be worthy of study is a daunting process, especially A Vaccine Journey -- logo for COVID-19 vaccine serieswhen it is against a novel or emerging virus. It can take years just to identify which parts of the virus the vaccine should target to allow the immune system to protect against viral infection. In the case of COVID-19 (SARS-CoV-2) researchers had several key bits of information that helped them in the race to develop a vaccine.

Firstly, recent advances in technology allowing rapid and accurate sequencing of genetic code enabled scientists in China to sequence the genetic code of the virus within days of the first identified cases of COVID-19, back in January 2020. Having the genetic code is a critical starting step to construct a vaccine. The Chinese researchers then posted the full sequence of SARS-CoV-2 on a public access site and shared it on a public genetic sequence bank . This allowed scientists across the globe to rapidly analyze the virus and quickly design vaccine candidates that could drive immune responses that target vulnerable parts of SARS-CoV-2. Subsequently other scientists and journals worldwide published their research data on SARS-CoV-2 in an unprecedented open access format which facilitated sharing of data, experience and models to help to drive forward our knowledge of the virus at an unusually fast pace .

Secondly, scientists weren’t starting on the vaccine from a standing start. Coronaviruses have been studied for many years and virologists already had key bits of knowledge on how these A Vaccine Journey series--bottle of vaccine and syringeviruses enter cells and replicate . This research provided information on which bits of the virus we should aim to target the immune response against.

Additionally, outbreaks of the related coronaviruses SARS-CoV and MERS-CoV in the 2002 and 2012 outbreaks respectively had pushed research toward the design of vaccines that could drive protective immune responses to these viruses; for example a MERS adenovirus vaccine reached clinical trials and was developed by an Oxford research group that went on to develop one of the COVID-19 vaccines in partnership with AstraZeneca.

The fast pace of vaccine development has also been influenced by work conducted on RNA vaccines, a strategy that began decades ago and now figures in two of the leading COVID-19 vaccines. This has given us a much wider range of potential vaccine types than just conventional vaccines which use whole inactivated virus or viral proteins. This emphasizes how years of academic ‘blue skies’ research feeds into translational research and the design of better medicines and vaccines.

This combined knowledge together with the huge amount of funding that has been pumped into SARS-CoV-2 research by not only biotech and pharmaceutical companies but also from charitable foundations and government funding has helped to greatly accelerate vaccine development at all phases of the vaccine development pathway.

Finding the optimal immune response

Coming back to the very basics of vaccine research or the discovery phase; when vaccine candidates are being designed, it is important early on to identify the relevant viral antigens—the fragment of the virus which can drive an immune response—that are most likely to generate the best immune responses against SARS-CoV-2. Vaccination is all about stimulating the immune system, in a controlled manner, to recognize and generate ‘memory’ to a specific pathogen, in this case SARS-CoV-2. Ideally the vaccine will stimulate two parts of the immune system . Firstly, B cells, which produce protective antibodies against a pathogen. These antibodies can, or example, A Vaccine Journey Part 1 -- image is of SARS-COV-2 w/antibodiesblock the virus from entering our cells. Secondly, vaccines often activate several kinds of T cells, which help B cells function (CD4 helper T cells) and kill cells which are infected by the virus (CD8 killer or cytotoxic T cells). Importantly, the vaccine must drive a protective response that generates T cell and B cell memory so that when we encounter the virus for real our B cells and T cells are primed to spring into action much more quickly than if they were seeing the virus for the first time . Vaccines are able to educate our immune cells by exposing the immune system to the pathogen in a controlled manner , for example by transferring inactivated or noninfectious parts of the virus into cells or even delivering instructions to cells on how to transiently make parts of the viral target of interest.

For COVID-19, the majority of vaccines have focused on generating immune responses which target the spike protein of SARS-CoV-2. The spike protein is the part of the virus that binds and allows the virus to enter and infect our cells; if we can block this binding then we can block infection. This is the job of antibodies which recognize and bind the spike protein preventing the virus from entering our cells. For any cells which do become infected with the virus, killer CD8+ T cells would recognize these cells and eliminate them. Virtually all the vaccine candidates in the pipeline contain the spike code or antigen with the aim of generating T and B cell immune responses against the spike protein of COVID-19.

A centuries-old process

The speed of development of COVID19 vaccine design has been unprecedented and demonstrates what can be achieved when enough money, collaboration and years of scientific research and knowledge are focused on one objective. The development of these vaccines, although on the surface amazingly quick, occurred due to the accumulation of knowledge from years of research into both the coronavirus family and the design of new ways of delivering vaccines. We have come a long way since the 1790’s when Edward Jenner first termed the word ‘vaccination’ to describe how inoculation of people with cowpox protected them from infection with smallpox – a disease that has been eradicated from the world by vaccination.

Immunology expert Rhiannon Jenkinson, PhD, is Director of Science at Charles River Laboratories, Portishead, where she leads projects for clients in the fields of autoimmunity, inflammation and oncology. Her site worked on a number of the COVID-19 vaccines and drugs.