In June 2021, the Head of NHS Providers Chris Hopson told Times Radio that COVID-19 vaccination boosters may become necessary for the next ten years. He said that vaccines would “probably” be administered “on an annual basis for…at least five, six, seven, eight, nine, ten years”. Currently, it is expected that the entire adult population in high-income countries will be fully vaccinated by late 2021. Since the outbreak of COVID-19 in December 2019, the speed of vaccine development, clinical trials, efficacy and then rollout, has been at the forefront of everybody’s mind. But as we emerge from an emergency response to a more sustainable immunization plan, utmost thoughts turn to pipeline booster programmes.
To understand the future of vaccinology, we must first look at its past. The success of the COVID vaccines build on the long history of vaccine innovation and development. Devoid of high-tech analytics, potency and safety early vaccines were predominately based on animal models. Despite stunning successes of global immunisation programs, the late 1970s and 1980s saw complacency and in some cases growing resistance to vaccines which led to a decline in both profitability and the number of vaccine manufacturers. While those trends had largely reversed in recent years, it was the emergence of the COVID-19 pandemic that would change the vaccine landscape forever.
COVID-19 has been a game-changer. With the rapid development and emergency use authorisation of two-dose jabs from Pfizer, Moderna and AstraZeneca, and Janssen’s single dose, vaccinology has been brought to the forefront of both scientific discovery and public consciousness. While all of these new vaccines represent novel delivery platforms for commercialized vaccines – it is the mRNA-based products deployed by both Pfizer and Moderna that are truly paradigm-shifting. The mRNA vaccines, which trigger an immune response via delivery of a lipid-encapsulated mRNA molecule coding for the target protein antigen (in this case, the COVID-19 Spike protein) is very quick to design and develop. The subsequent intracellular translation and expression of the Spike protein antigen has been shown to trigger a potent and protective immune response in clinical trials and real-world application. We have also seen, with the advent of more traditional protein-based vaccine candidates such as SCB-2019, structure-guided antigen design. These vaccines utilize a recombinant S protein subunit vaccine candidate and a specific mutation that locks the protein in a pre-fusion to produce a higher rate of protective immunity against COVID.
This unprecedented speed to commercialisation was arguably the most successful component of the global roadmap out of emergency. Even before the World Health Organization declared COVID-19 to be a global pandemic on March 11, 2020, developers worldwide scrambled to find an effective vaccine. While new vaccine development typically takes 10-15 years, the Pfizer and Moderna vaccines were authorized in the US in December 2021, and the Oxford-AstraZeneca vaccine began distribution in January 2021. In addition to unprecedented urgency and resources dedicated to development, emergency use authorisation by multiple health authorities have enabled rapid commercialisation of several highly effective vaccines. According to researcher Wieslaw Swietnicki at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, “the speed and flexibility of the regulators” ensured the impressive vaccine rollout.
The urgency and demand for protective vaccines during the pandemic also widened the commercial playing field almost overnight. there was more leverage within the vaccine manufacturing landscape. This is dramatically illustrated by Moderna, which had never before licensed a single product, becoming a leading mRNA-based vaccine in the US. Potential requirements for booster jabs, as well as the urgent need to expand vaccine availability beyond developed nations, continue to expand the need for vaccine discovery and refinement. With COVID variants now appearing throughout the world, vaccinology will remain a pioneering and principal component of scientific discovery.
So, what can we expect from the future of vaccinology? Bruce Carpick, Global Analytical Expert at Sanofi Pasteur highlights the need for advanced vaccine analytics. Testing helps to control both the product being produced and the manufacturing process. For Carpick, vaccine analytics enables scientists to both “test at multiple stages and manage the analytical lifecycle of vaccine products”. Key product attributes include safety, potency, purity, structure, and stability. To ensure this the vaccine landscape would benefit from regulatory harmonisation between global health authorities, such as WHO and ICH, and individual regulatory bodies, and national pharmacopoeia.
Collaborations between industry and academia will also be key. Paul Kellam, Vice-President of Vaccines and Infectious Disease at Kymab described the issue as pertaining “particularly to the need to fund and fund it properly on both sides”. Production costs tend to be much higher for industry than for academia and these partnerships when joined by the primary purpose of vaccine development instead of market competition, foster rapid innovation. One example of a successful collaboration between industry and academia is the CARB X initiative. CARB-X is a non-profit effort headquartered at the Boston University School of Law, created in response to the U.S. government’s 2015 Combating Antibiotic Resistant Bacteria (CARB) initiative.
The move towards advanced manufacturing methods in vaccine development, means scientists like Bruce Carpick expect to see “a phenomenon that I would describe as industry 4.0 or biopharma 4.0”. The ‘phenomenon’ refers to the application of smart factories and digital manufacturing. This will allow for continuous and smoother manufacturing. One expectation of computational vaccine technologies is that they can provide a solution on a global scale. As Wieslaw Swietnicki points out, while the COVID “vaccination is one of humankind’s greatest inventions, it is not equally distributed”. Although the industrial West have nearly vaccinated entire populations, much of the world still have no access to COVID vaccines. A global roll-out initiative must occur.
However, the difficulty in providing a global roll-out concerns the issue of storage. Some mRNA-based vaccines such as the Pfizer product must be shipped on dry ice and frozen up until a couple of days before use. This will prove an uneconomical and labour-intensive operation, especially for developing nations. Single-dose vaccines that can be refrigerated or even stored at ambient temperature will prove a more cost-effective solution to systematic global immunisation. Another potential challenge will be to leverage the same level of rapid commercialisation in response to COVID variants. Having clearer regulatory expectations along with a streamlined approval process will be crucial to rapidly confronting this and potential future pandemics.
As we vaccinate our way out of the pandemic, and with routine booster jabs possibly being required for the foreseeable future, scientists must address the frightening possibility of resistance. One of the biggest threats to drug efficacy, resistance is a naturally occurring phenomenon. Over time, repeated drug use becomes ineffective and makes treating viruses like COVID-19 more difficult. Sustaining the current approach to vaccine development may also be impractical. Vaccine candidates based on different short fragments of the spike protein S means their limited antigenic repertoire is easily bypassed by mutations of the COVID pathogens. To help solve the problem, the targets must be multiple. Currently, the only approved inactivated virus vaccine is the Chinese version made by Sinovac. However, with the continued collaborative and rapid efforts to suppress the harmful spread of COVID, the future of vaccinology looks promising. As innovative technology advances and distribution strategies become realised, the fight against coronavirus and its variants is sure to continue.