R&D: An Expanded Playbook

The story of how British doctor Edward Jenner serendipitously discovered a way to inoculate people against smallpox in 1976 by injecting them with cowpox pus is well-known. Over the past two centuries, vaccine development platforms have (thankfully) advanced leaps and bounds, delivering a wealth of options to tackle global health challenges.

The story of how British doctor Edward Jenner serendipitously discovered a way to inoculate people against smallpox in 1976 by injecting them with cowpox pus is well-known. Over the past two centuries, vaccine development platforms have (thankfully) advanced leaps and bounds, delivering a wealth of options to tackle global health challenges.


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The oldest biologic in the world

In essence, vaccines expose the body to a small amount of antigen from a specific pathogen so that the body produces antibodies, which can eventually be used to fight off any potential future exposure to that pathogen.

There are two basic types of vaccines:

  • Live attenuated vaccines, produced by modifying a disease-producing virus or bacterium in a laboratory
  • Inactivated vaccines, which compose either whole or factions of either viruses or bacteria

Vaccine platforms

One of the most important innovations in vaccinology, as identified by GSK Vaccines R&D SVP Dr. Emmanuel Hanon, is the introduction of new platform technologies. He explains, “this means working on a certain vaccine approach and, once you have collected the learnings of that approach, you can apply this to different pathogens and create a family of vaccines. This is what we have done in Belgium with the development of our adjuvant technology, where we use a given adjuvant in several different vaccines. The benefit of a platform technology is that you make the investment once but it benefits a variety of vaccines.”

Essentially, vaccine platform technologies are based on a platform base carrier, which can be modularized with the targeted antigenic component of the pathogen. In theory, once designed and licensed for one vaccine, the same platform can then be used to develop future vaccines by simply substituting the antigenic component, resulting in faster and cheaper development.

Once designed and licensed for one vaccine, the development of future vaccines using the same platform should simply require substitution of the desired antigenic component, enabling faster and cheaper development, regulatory approval and mass production.

Some common platforms include:

  • Adenoviral vectors
    As the name suggest, adenoviral vector vaccines use adenoviruses as a vector to deliver target antigens to the body. Adenoviruses are non-enveloped, double-stranded DNA viruses that typically cause mild respiratory and gastrointestinal tract infections in people. Janssen’s Ebola vaccine, approved in the EU in 2020, uses their adenoviral vector type 26 platform, which they have been developing for over ten years.
  • Bioconjugation
    A conjugate vaccine is a substance that is composed of a polysaccharide antigen fused to a carrier molecule, which enhances the stability and the effectiveness of the vaccine. The most commonly used conjugate vaccine is the Hib conjugate vaccine, which is used to prevent infection caused by the type b (Hib) bacteria. The majority of countries worldwide include this in their routine immunization schedules.
  • mRNA
    A revolutionary ‘new’ technology – scientists have been researching mRNA vaccines for decades but prior to 2020, no mRNA vaccine or mRNA therapeutic had been approved for any kind of use globally – that has already proven its mettle in the COVID-19 crisis, unlike conventional vaccines, mRNA vaccines do not carry a weakened or inactivated pathogen into the body. Instead, it gives the body instructions to manufacture a protein from the pathogen that triggers an immune response.

However, as Canadian biotech company Acuitas Therapeutics CEO Dr. Thomas Madden cautions, companies should remain open to new technology platforms, even if they have invested significantly in others. “Personally, I think Big Pharma can sometimes feel trapped by the scale of investments they have made. If a company has invested USD 5 billion in manufacturing plants based on a particular technology, it would potentially be political suicide to suggest that they move away from that technology. We should always be open to evaluating new ideas and to accepting that better approaches may exist out there, as opposed to saying that, well, we have always done it this way, so we will continue to do it this way.”

He acknowledges that, at least when it comes to mRNA technology, “companies do seem open to collaboration”, adding, “there are three major mRNA companies today: CureVac, BioNTech and Moderna. Obviously, BioNTech has partnered with Pfizer, and CureVac recently announced a major collaboration with GSK, so there are opportunities to work together to gain expertise and technology from major players in this new field.”


An adjuvant is a pharmacological or immunological agent that improves the immune response of a vaccine and therefore minimizes the dose of antigen needed within each vaccine dose. The global vaccine adjuvants market, while still relatively small at around USD 769 million, has nearly doubled in the past five years.

For instance, GSK’s shingles vaccine, Shingrix® has been the principal growth driver for the company’s vaccines business in the past couple of years. The “secret sauce” for Vaccines Head Roger Connor is the adjuvant used, which has been proven “to have an impact on age-related decline in immunity.” For him, adjuvants are an essential aspect of developing vaccines more effective in the elderly population, whose immune systems have naturally declined with age. “The adjuvant technology we have is a backbone technology that already exists. We are [also] using this [adjuvant] in other older adult vaccines like our respiratory syncytial virus (RSV) candidate”. After all, he emphasized, “if we can switch the world on to older adult vaccination, that will have a very big impact on public health.”

HIV – the Holy Grail of the vaccines industry

The quest to develop a HIV vaccine has been underway since its identification in 1984. However, the virus has proven itself a formidable beast, evading the efforts of top researchers and scientists to corral.

As Dr. Johan Van Hoof, Global Therapeutic Area Head of Vaccines at Janssen emphasizes, “the main reason there is still no HIV vaccine after 30 years is the scientific challenge,” explaining, “even now, we do not know with certainty what kind of immune response is needed to overcome HIV, which makes it extremely difficult to develop a vaccine for it. Almost no one clears HIV themselves. The HIV virus is extremely smart, mutable and adaptable.”

Despite “HIV vaccine development [coming] with a lot of risk”, Janssen has persisted in its efforts and is today conducting a Phase 2b trial in high-risk women in South Africa. They expect to have a readout by the middle of this year. Dr. Van Hoof indicates, “we have developed various generations of a HIV vaccine, applying the principles of translational medicine … We are still in the middle of the process but we are cautiously optimistic about our vaccine candidate.”

Therapeutic Vaccines

An increasingly hot field, therapeutic vaccines are administered after infection to activate the patient’s immune system to fight off the disease. The first therapeutic vaccine was approved by the US FDA in 2010 to treat prostate cancer. Still being prescribed today, its 2019 list price in the US is USD 120,000.

However, while therapeutic vaccines belong in the category of immunotherapies alongside their far more successful siblings of checkpoint inhibitors and CAR-T therapies, thus far they have demonstrated far more disappointing clinical results in oncology. While a number of strategies have been tried, they still fail to demonstrate any clinical benefit as monotherapy in patients with advanced disease. For this reason, researchers currently believe that therapeutic vaccine approaches will need to be assessed and developed in combination with an arsenal of other cancer-fighting platforms.

Nevertheless, convinced of the potential value of this approach, a number of Big Pharma players are investing in the overall space. In 2019, Boehringer Ingelheim spent USD 394 million to acquire AMAL Therapeutics, a Swiss cancer vaccine player. AMAL’s lead vaccine ATP128 is currently developed for stage IV colorectal cancer and was developed through its technology platform KISIMA. The KISIMA platform enables the assembly of three functional components – one for antigen delivery, one as an adjuvant, and one “multi-antigenic cargo” that can be tailored for various indications – into one patented fusion protein that can then be used as a vaccine.

As GSK Dr. Hanon highlights, “therapeutic vaccines have the ability to treat an ongoing disease or to prevent the cyclic evolution of that disease. GSK has several vaccine candidates in our platform that have this property. Our vaccine preventing shingles is one example and has 90 percent efficacy, across different ages. It is administered to people many years after they have been infected by the virus and is still able to recalibrate the body’s immune system against the virus so that it never comes back, or at least does so with very low frequency.”

COVID-19 and vaccine R&D

The ongoing global pandemic has focused attention on the vaccine sector in an unprecedented manner – for better or worse. As European Vaccine Initiative (EVI) executive director Ole Olesen sums up, “looking at the big picture, the COVID-19 situation has generated a lot of global interest in vaccines, whether from public funders and private investors or amongst the general public. Whereas previously vaccines were a little out of fashion, now people see the importance of vaccine R&D quite clearly. This is very positive for organizations like us because we benefit from this sort of general advocacy and awareness around the importance of vaccines.”

However, he hopes that global stakeholders understand the true, long-term nature of vaccine R&D. “As a community, we have to seize this opportunity to stress that vaccine development needs a long-term perspective. We are seeing some unrealistic expectations within the political communities in both the US and Europe surrounding what vaccine developers can do in the short term. I hope this longer-term awareness of the critical importance of vaccine R&D can be a positive takeaway from the COVID-19 experience.” He also hopes that investors, politicians and other actors understand the exceptional nature of COVID-19. “We do not want investors or the public or other stakeholders to start questioning why vaccine development for other diseases takes such a long time in comparison. The COVID-19 virus may turn out to be relatively simple to develop a vaccine for but diseases like malaria, tuberculosis and HIV are extremely complicated.”

Manufacturing & Supply Chain Complexity


Pharma industry insiders view vaccines as one of the most challenging products to manufacture, fundamentally due to the inherent biological variability of the pathogen itself, which is the starting block of any vaccine, as well as the resulting inherent variability of the biological raw materials and processes required in vaccine production. For this reason, the product is very much the process when it comes to vaccine manufacturing. This has also been attributed as one of the main reasons for the relative scarcity of vaccine players globally.


Population Health: Access & AntiVax Challenges


Vaccines have been touted – and rightly so – as the most cost-effective health intervention after access to clean water. It is estimated by global health institutions that vaccines save at least three million lives every year. While tremendous progress has been made since the discovery of vaccines in the 19th century, significant coverage gaps persist and in many countries, a worrying trend of vaccine reluctance threatens to undo many of the achievements brought about by public immunization programs.


Business Models & Market Access


While perhaps not as lucrative or – prior to COVID-19 – as attention-grabbing – as other areas of the pharmaceutical industry, vaccines are also not the forgotten backwaters that many industry insiders seem to view them as. While the inherent complexities related to vaccine R&D do impose high barriers to entry and significant costs, new collaboration…


Securing Trust in the COVID-19 Supply Chain: From Development & Delivery to Acceptance & Administration


Scientists have come together in an unparalleled worldwide collaboration and sharing of data to advance a COVID-19 vaccine. As rollouts become reality, stakeholders from across the globe will need to collaborate to ensure these vaccines are available and accepted. Vaccines will need a high level of trust for a return to normal. Trust will be a cornerstone for the successful launch, distribution, and acceptance of vaccines.