Why do SARS-COV vaccines not exist? The pharma scientific intelligence and business model must be revisited!

KEYWORDS:

• Drug discovery
• pharma industry
• biotechnology
• Covid19

1. Introduction

When the President of United States, Mr. Donald Trump, stated that COVID19 had taken the world by surprise, it was a damnation on the strategy and predictions of all business-driven therapeutic discovery and developments, including big pharmaceutical and biotech companies. For the academics, the pandemic was no surprise.

In 2004, Dr. Hughes from the National Center for Infectious Diseases, Center for Disease Control and Prevention, Atlanta, GA, wrote an interesting article titled ‘SARS: an emerging global microbial threat’ [1]. Dr. Hughes stated that in March 2003, the Institute of Medicine (USA) had published an update in its 1992 landmark report on emerging infections describing the global microbial threats and factors affecting their emergence or resurgence and measures that should be undertaken to effectively address them [2,3]. In the same year, SARS emerged as true evidence of this report. Hughes advocated for a global collaboration in the development of rapid diagnostics, new therapies, and vaccines, implementation of aggressive evidence-based infection control strategies and effective communication.

In November 2002, Foshan in China witnessed the first case of severe acute respiratory syndrome (SARS) [4]. More cases were detected in other regions of China. In Feb 2003, around 400 cases were reported, the majority were health care workers [4]. Infected individuals further spread the disease to other Asian countries, including Hong Kong, Vietnam, among others. By March–April 2003, it had affected 27 countries with a total of 8,096, including 774 deaths in 27 countries [5]. The epidemic reemerged 10 years later. In the summer of 2012, the virus once again hit this time the Arabian Peninsula with patients dying via acute pneumonia and renal failure [6]. A novel coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV) had been identified [6]. In the spring of the same year, similar cases occurred in Jordan and were retrospectively diagnosed as MERS [7]. The MERS-CoV also affected other countries through asymptomatic patient travels. Almost 2000 cases have been confirmed including nearly 700 deaths in almost 30 countries [8,9].

The MERS-COV, SARS-COV, and COVID19 belong to the subfamily Coronavirinae in the family of Coronaviridae of the order Nidovirales, and this subfamily includes four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Coronaviruses are minute (65–125 nm in diameter) encapsulated viruses with a crown-like appearance under an electron microscope, due to the presence of spike glycoproteins on the envelope. Coronaviruses have large (26–32 kbs) single-stranded, positive-sense RNA genomes. The viral particles contain four main structural proteins. These are the spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins [10].

Both SARS-COV and MERS-COV infection died out as their transmission rate is less and they were easily contained compared to COVID19. As estimated by World Health Organization (WHO), the reproductive number (R₀) for COVID19 ranges between 2 and 2.5 that is higher than that for SARS (1.7–1.9) and MERS (<1), and thus explaining why COVID19 transmission speed is higher and has a higher pandemic potential. Moreover, SARS and MERS were associated mainly with nosocomial spread, whereas SARS-CoV-2 is much more widely transmitted in the community [11].

During the 2003 SARS epidemic, there was a statement from big pharmaceutical companies to engage in the fight of the epidemic and the world had hope of a vaccine within a few years [12,13]. Seventeen years later and still, there has been no vaccine produced against SARS-COV and MERS-COV. SANOFI claimed to have worked out a program to produce a vaccine against these deadly viruses, but this was dropped without any further statements from the company [14]. The company is reviving the program to help in the fight against COVID-19.

In analyzing the effort to develop a vaccine against SARS-COV and MERS-COV, since 2003 up until the recent outbreak of COVID-19, only academic institutions have been involved. As stated in the WHO website [15], there are 33 vaccines in development using either virus-like particles, DNA, virus protein, or non-replicating viral vectors. The majority (30 out 33) of these efforts are from academic institutions, in particular, from China. Of these 33, only 4 are currently being in clinical trials. Two in Phase 1: one from the Chinese Center for Disease Control and Prevention the second from the USA National Institute of Allergy and Infectious Diseases (NIAID). The other two are in Phase III: one from Institut Pasteur, France and the second from Novavax. For the MERS-COV, there is only one vaccine that is being developed by Oxford University and King Abdullah International Medical Research Center (KAIMRC) at the stage of Phase 1 clinical trial.

In summary, this raises a poignant question. Since 2003, why was a vaccine not developed against SARS-COV and MERS-COV, even though academics have alerted the world about the impending danger of an epidemic? The reasons given for not developing SARS-COV and MERS-COV vaccines are the lack of adequate funding as well as poor understanding of the viruses’ biology despite the candidates' vaccines for both viruses showed good immunizations in animal models [16,17].

However, a simple answer can be found by analyzing the vaccine development strategy against SARS-COV and MERS-COV and is essentially down to the non-engagement of big pharmaceutical companies in the efforts to develop a vaccine. The matter has been left to academics with limited resources in this field.

Due to the notable absence of big pharmaceutical companies in developing a vaccine against SARS-COV and MERS-COV since the emergence of those epidemics, it is important to question their Scientific Intelligence prediction as well as their business model. The pharmaceutical and biotechnological sector is a profitable research institution, constantly reevaluating their portfolio to find and engage in more profitable projects. However, their failure in engaging in a SARS-COV and MERS-COV vaccine development since 2003, we must question their scientific intelligence. Had they engaged in the efforts and followed the predictions made by academics in the field, they would have by now developed a vaccine against SARS-COV that could work in protecting 30–40% against COVID19 due to the similarity of the two viruses [18]. The other element to why major pharmaceutical companies did not engage in this effort is because the SARS-COV and MERS-COV markets were too small! Instead, the new strain of swine-origin H1N1 as a pandemic that only appeared in June 2009 and declared by WHO as a worldwide pandemic on August 2010. The confirmed deaths were estimated at between 151,700 and 575,400 [13]. On 11 November 2009, the Influenza A (H1N1) 2009 monovalent vaccines were approved for use in the United States. Four out of five vaccines were produced by major pharmaceutical and biotech companies [19] as the patient population was larger than that of SARS-COV and MERS-COV

2. Expert opinion

Big pharmaceutical companies are the driving force in leading innovative and competitive research to discover and develop new therapies. Without them, medications to cure devastating diseases that include Ischemic heart disease, stroke, chronic obstructive pulmonary diseases, lower respiratory infections, diabetes mellitus, Alzheimer’s disease, and cancer would not have been produced. These were created based on product-focused research unlike academic research that mostly pursues non-product aimed research. In addition, these large corporations select the best scientists, business developers combined with excellence in management proficiency. As big pharmaceuticals aim for a profitable research, most of their portfolio target diseases affecting a large population to enable them once they sell the drug to firstly cover the high expenses related to discovery and secondly to develop new drugs as well as make a large margin of profit.

Unfortunately, this strategy is not always successful and can cause the big pharma to miss golden business opportunities. In many cases working on diseases that have a smaller number of patients such as rare diseases, MERS-COV and SARS-COV, would have streamed line the big pharmaceutical company process to rapidly respond to diseases that are of similar kind but affect a large number of patients once emerged. Most of the big pharmaceutical companies avoid working on rare diseases because the number of patients is lower; however, what is often forgotten in work on rare diseases is that most of them have unique mechanisms with their cells having unique functional biology. Their metabolisms switch from one pathway to another to adapt and understand the functional biology of these rare disease cells that would enable scientists to apply the gained knowledge to other diseases such as cancer and inflammation as example.

Similarly, the development of a SARS-COV and MERS-COV vaccine has been avoided since 2003 because the market size of these vaccines was assessed to be small by the big pharma that possess the capabilities to discover and develop vaccines. However, what these pharmaceuticals also missed was the report published by the WHO with academic researchers advocating that these coronaviruses will hit the globe at any time. The risk to develop a vaccine for SARS-COV and MERS-COV was not taken; otherwise by now, the world would have a vaccine that could have worked by at least 30–40% in the COVID-19 [18].

Based on this analysis, the business model employed by big pharmaceutical companies must be revisited and may start considering working on diseases that have less market share to gain more knowledge and to also be ready for any unexpected global diseases. The COVID-19 pandemic has taught the globe a valuable lesson in such that all need to revisit their business model and that includes the big pharma, they have missed both a big business opportunity and great impact to help the humanity.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This manuscript was not funded.