Amsterdam institute for Immunology and Infectious diseases

In July 2023, Prof. Rogier Sanders received an honorary doctorate from the University of Southampton in recognition of his significant contributions to virus and vaccine research. His groundbreaking discovery involves a protein-stabilizing method that enhances the effectiveness of vaccines against various viruses. While initially focusing on the HIV virus, Sanders' innovative approach extends to the vaccination of other viruses, including COVID-19. Notably, most COVID-19 vaccines, such as Pfizer, Janssen, and Moderna, incorporate the techniques pioneered by Rogier, benefiting hundreds of millions of people. Since 2016, Sanders has held the position of Professor in Virology, specializing in Experimental Vaccinology. Given his honorary doctorate we interviewed Prof. Sanders about his work throughout the years.

Prof. Sanders reflects on the origins of his research: "It began with a paper from my PhD, more than two decades ago. While this paper sparked our journey, we did not fully understand the mutations we made at the time. It took ten years for clarity to emerge, though we had our suspicions."

Prof. Sanders' approach revolves around stabilizing the HIV spike protein, the virus's outer protein critical for generating protective antibodies. He analogizes these proteins, including the HIV envelope protein, SARS-CoV-2 spike, and RSV-F, to mousetraps, under tension until triggered. When encountering a nearby target cell, the protein binds to its receptors, initiating closure, protein modifications, and fusion of the virus membrane with the cell material, resulting in the post-fusion state of the HIV envelope protein.

Vaccines using wild-typ, i.e. non-stabilized viral envelope/spike/fusion proteins have a tendency to spontaneously transition to the post-fusion state (the mousetrap springs prematurely), generating antibodies that struggle against infection. Prof. Sanders explains it as a vaccine acting on closed mousetraps, unable to address open ones, which is the actual target for protection. The Respiratory Syncytial Virus (RSV) illustrates this challenge vividly. In the 1960s, vaccines were developed that unknowingly presented the post-fusion form of the RSV-F protein, inadvertently exacerbating the disease in vaccinated babies instead of offering protection. It was not until about 50 years later that it was considered safe to work with RSV vaccines again.

Advances in Virus and Vaccine Research through Protein Stabilization

Through the research of Prof. Sanders on the HIV spike protein and work on the RSV-F protein that benefited from a critical contribution of Hergen Spits, Professor of Cell Biology at Amsterdam UMC, and Tim Beaumont, Senior Scientist at Amsterdam UMC, protein stabilization has been achieved which is very important in the development of vaccines. Prof. Sanders clarifies, "In essence, by introducing the amino acid Proline at a specific location in the HIV envelope protein, we can prevent its transition from the pre-fusion state to the post-fusion state. This ensures the proteins remain in the pre-fusion state, enhancing virus antibody production. As mentioned earlier, this discovery dates back to 2001, but it took us a decade to fully grasp its mechanics. Hans Langedijk, Director of Subunit Vaccine Design at Janssen Vaccines and Prevention, successfully applied the Proline technique to the RSV protein. Jason McLellan and Andrew Ward achieved success with MERS and SARS in 2017, and by early 2020, it proved effective for the SARS-CoV-2 virus. The Proline modication is now a key component in almost all COVID-19 vaccines."

Prof. Sanders' Journey into HIV Research

Prof. Sanders initiated his HIV research during his studies in Medical Biology at the University of Amsterdam. He recalls, "I noticed a piece of paper on the availability of an internship position in the same department as where I am currently employed, and it immediately piqued my interest. The idea of such a simple, small virus being so effective and having such profound consequences fascinated me." Following an internship in fundamental HIV-1 Virology, under the supervision of Dr. Koen Verhoef and Prof. Ben Berkhout, Prof. Sanders undertook another internship in New York in the group of Prof. Johne Moore, delving into HIV vaccine research. He describes the shift, saying, "Fundamental research aims to unravel the workings of nature, but in vaccine research, you get to be inventive, crafting and adjusting molecules and proteins. This challenge greatly appealed to me—manipulating the immune system to achieve specific goals."

From COVID-19 Successes to the Complex Realms of HIV and HEP-C Research

In recent years, Prof. Sanders' research included work on COVID-19, but it has now reverted back to HIV research. Prof. Sanders acknowledges the frustrations inherent in HIV research, where many ideas often prove ineffective. Therefore, the COVID-19 experience with successful vaccine and antibody approaches provided a positive contrast. While COVID-19 presents challenges, particularly with new variants, it pales in complexity compared to HIV. Currently, Prof. Sanders and his team are actively engaged in human-based vaccine research, yielding promising outcomes for future applications. Additionally, he has embarked on a new and complex journey with the hepatitis C virus (HCV). Recently, research of Prof. Sanders’ group in Science unraveled the previously elusive structure of the HCV envelope protein. Armed with this knowledge, they are now ready to manipulate it, thanks in part to a significant grant awarded to his colleagues, Kwinten Sliepen and Janke Schinkel. In contrast to the relative simplicity of COVID-19, the complexities of HIV and HCV continue to captivate Prof. Sanders, leaving him eager to uncover new discoveries in the years to come.

Diversity in Virology and Vaccines

"The foremost challenge in virology and experimental vaccinology is diversity. Some viruses exhibit diversity, complexity, and rapid mutation rates, enabling them to potentially evade immune responses induced by vaccines or the natural infection over time. This challenge is most pronounced in the cases of HIV and HCV, but it also applies, in a lesser degree, to COVID-19 and influenza. We have long discussed the idea of 'Universal Flu Vaccines,' capable of providing immunity against all flu strains. However, to be entirely candid, this goal remains a formidable challenge. While influenza may not exhibit the same level of diversity as HIV and HCV, annual revisions of flu vaccines are still required due to viral changes. Tackling this diversity and discovering solutions for it unquestionably represents the foremost challenge in the field of virology," Prof. Sanders emphasizes.

Guidance from Prof. Sanders

Prof. Sanders, Virology professor and recent recipient of an honorary doctorate from the University of Southampton for his virus research contributions, gladly offers his valuable advice to aspiring young researchers. He emphasizes the importance of having a unique, passionately pursued idea, stating, "In the competitive scientific world, following what others are doing is going to be challenging. When you discover something unique and believe in it, do not give up too quickly. Consider my 2001 Proline mutation discovery—it took a decade to realize its significance for HIV, another 5 years for broader applications, and 20 years in total for a major breakthrough with its application in the COVID19 vaccines . Despite funding challenges for years after the initial discovery, I held onto it as my primary focus. Even when other areas received funding, this research remained close to my heart, and it eventually succeeded. My advice: persevere."

Prof. Sanders underscores the vital role of collaboration for young researchers, stating, "View research collaborations as a journey of trial and error. They may not always work, but with the right partners, remarkable collaborations can thrive. Seek those with complementary expertise, and when you find them, nurture these partnerships. The most profound scientific progress often emerges from collaborative endeavors."

Leading the Amsterdam UMC Big Band

Alongside his successful scientific career, Prof. Sanders serves on the Health Council in the committee for Vaccinations. Moreover, he holds a chairmanship in addition to his research endeavors – he chairs the Amsterdam UMC Big Band, where he also showcases his trumpet skills.

For more information contact Prof. Rogier Sanders or read his scientific articles.

Image Prof. Sanders (left) together with the University of Southampton nominator, Prof. Max Crispin (right).

Text: Esmée Vesseur