Science provides a unique viewpoint to the world, build on empirical evidence that allows modelling of the truth, so the world becomes predictable upon manipulation.
However, academic science does not provide any direct or calculated societal gain and can therefore be viewed as a charity case. There is an historical “contract” between science and charities (or society) that science produces reliable knowledge, provided it communicates its findings back to society299. Academia in principle is provided with autonomy to engage in science and teaching, although this is based on the trust of the agreement299. Initially structured as a top-down structure, society has increasingly been involved in scientific conduct and its directions299–301. Science funding is becoming more defined as “science for the masses” and scientists are adapting by playing on the needs of the masses302. Unsurprisingly, a vaccine or cure of an untreatable infectious disease or cancer is among those needs and is increasingly incorporated in research plans as a goal. However, vaccine development takes an average of at least 10 years from pre-clinical discovery to market entry, with a 94% fail-rate303. With an average cost between $165-289 million, any academic scientist applying for grants promising the next vaccine is dreaming. In fact, the major source of cost inflation of vaccine development is the indirect costs associated with different levels of experience in the organizations developing the vaccine220. Therefore, the requirements of cost-effective development of vaccines is best done by experienced pharmaceutical companies within the pharma framework instead of creative academic scientists (Figure 1). Still, scientists get funding with initially big claims and likely cannot (or will not) live up to the overstated impact, ultimately leading to loss of trust in science and a gap between society and academic scientists.
Academic science has a unique position as it is not tied by the capitalistic framework of pharmaceutical companies that require direct or credible return of investment. As such, there are some important counter arguments to be made for academic science when therapeutic vaccination is concerned, especially in the form of anti-tumor vaccines (see also Thesis Part II). Cancer patients diagnosed with immune-suppressed tumors can be treated through immune-(re)activating biologics, which find their origin of discovery in fundamental knowledge from academic research. For example, the understanding of the PD1 inhibitory receptor constitutively expressed by virally exhausted T cells led to the discovery of similarly exhausted tumor-specific T cells (Chapter 9). Blocking these molecular processes (that keep T cell suppressed) using antibodies (termed immune checkpoint blockade; ICB) reactivated exhausted T cells in mice and later in cancer patients, leading to tumor eradication and revolutionizing cancer therapy304. However, more than a decade later, we still do not fully understand the complete effect of these blocking antibodies in both mice and humans, regardless of the initial hypothesis that led to clinical testing. Similarly derived from academia, the expansion of tumor-derived T cells ex vivo for infusion back into the same patient (passive therapeutic vaccination) has led to impressive clinical responses305,306. In both cases, pharmaceutical companies made clinical trials possible that were initially based on academic research. Hence, where the operating frame work of academia may provide unique explorative power, pharma has the executive power to drive the translational value of academic discoveries (Figure 1).
There are several factors to consider these impressive academic discoveries in the light of vaccine design. First, cancer patients are a group of patients with an immediate medical need and new therapeutic approaches can often be tested as a last resort. This is distinctly different from prophylactic vaccine development, where threats to health are less visible or immediate, healthy volunteers are required and side effects are of higher concern. Second, through our fundamental understanding of a cascade of abnormalities underlying a certain disease, we can hypothesize that removing a part of the pathological cascade will reduce or disrupt the disease. By analogy, removing one fundamental building block of a tower (disease), the whole tower collapses. However, understanding the position of every building block of a tower to build one (rational vaccine design), requires significantly more knowledge and testing. Third, the high prevalence of cancer in Western countries drives immediacy in public opinion towards anti-cancer therapies and subsequently funding. Lastly, and perhaps the most telling example is that of prophylactic human papillomavirus (HPV) cancer vaccination. Cervical cancer is caused by the HPV in virtually all cases and is the second most common cause of cancer-related death among women worldwide307. HPV non-infectious subunit vaccines, containing virus-like particles from the L1 major capsid protein of the virus, have shown extraordinary clinical efficacy in preventing cervical cancer308–310. However, the coverage of national HPV immunization programs is inadequate due to low public acceptance311,312, although the vaccination effects are clearly reducing the incidence of cervical cancer cases313,314. It is plausible the public is more tuned towards curing immediate illness instead of the prevention of the “chance” of disease, regardless of all the before mentioned downsides to curing compared to preventing. Academia seems suited to gain insight in understanding disease and pathology, which may lead to novel ways of interrupting existing disease processes and the development of novel cures. The realm of disease prevention (prophylactic vaccination) may be more difficult to leverage in a rational manner within the constraints of academia. Instead, academia may invest more in early detection of viable intellectual property (IP) that justifies additional funds and translational efforts. The translational value of their research may seem limited to academic researchers and requires alternative perspectives. In house IP scouts may not only generate additional funds from protected IP, but also provide the translational value that is expected by society, without devaluating the explorative power of academia.
In summary, there is clear merit for academics in testing novel therapeutic approaches based on a fundamental understanding of disease processes, but the goals should be realistic and overzealous claims should be frowned upon. Society will need to understand that science is not a grocery shopping list and that science can be unpredictable, regardless of the brilliance of the scientist or rigor of his/her experimental approach. In this regard, when academic scientists take their responsibility as teachers of society, expectations can be managed and the gap between society and academia may decrease. The gap between the explorative power of academia and the executive power of pharma may be bridged by experienced IP scouts capable of evaluating fundamental research results. Hopefully, academic research may regain the explorative power that has enabled revolutions like genetic engineering, electricity or X-ray radiography. As Jean-Claude Petit put it: “Actual breakthroughs, true discoveries, unpredictable and radical changes of world views can only emerge from fundamental research”315
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Sjoerd's thoughts on academic vaccine research 