In many parts of the world, vaccination programs have led to the elimination or drastic reduction of several major diseases, including polio, measles, and diphtheria. Some experts believe that cervical cancer (which in 9 out of 10 cases is caused by HPV) could soon join them in being virtually eradicated.
What is HPV and how does the HPV vaccine work?
HPV is not in fact a single virus, but a group of sexually transmitted viruses. Human Papillomaviruses are extremely common, and generally cleared up by the immune system without intervention, within a few years. Prior to the development of vaccines, HPVs were expected to infect nearly everyone at some point in their lives.
However, if certain HPVs remain in the system, over time they can significantly increase the risk of certain cancers, including anal, penile, vaginal, vulvar, oropharygeneal—and specifically cervical. Although HPV strains were found in cervical cancer tissue in the 1980s, they were only officially recognized as carcinogens in the 1990s, and it was another 10 years after that before we fully understood how many different strains of HPV could cause cancer.
The introduction of vaccination programs, beginning in 2006, have led to a significant reduction in the rates of cervical cancer, particularly in the developed world. However, both vaccine hesitancy and availability have still limited their success. With regards to availability, three key developments can increase access to vaccines in general: a) providing single-dose vaccines, b) making the manufacturing processes simpler and cheaper and c) increasing ease of transportation and storage.
Where are we today?
According to the World Health Organization (WHO) there are currently six licensed HPV vaccines worldwide—just three of which are licensed in the US: Gardasil, Gardasil-9, and Cervarix. All of these use Virus-Like Particle (VLP) technology, which represents a significant advance in immunology.
VLPs are a type of ‘Self-Assembling Vaccine’, which takes advantage of the ability of some viral proteins to spontaneously ‘assemble’ themselves into larger structures. These structures mimic the virus, and therefore prompt an immune response, but do not contain any actual viral material. One of their major advantages is their potential scalability, as proteins can be synthesized in a laboratory and then self-assemble under the right conditions. Another major advantage of VLP vaccines is that they can induce a strong immune response while maintaining a good safety profile, since they can’t cause disease.
However, VLPs do have some significant disadvantages. For a start, the production of VLP vaccines can be quite complex, with both the creation and purification of viral proteins being intensive processes. Some VLP vaccines can also require cold storage, which presents logistical challenges. These requirements and technical complexity naturally drive up the cost of VLPs, limiting their accessibility, particularly in low-income countries.
Furthermore, and perhaps most significantly, although VLPs are highly effective at inducing immune responses against a specific viral protein, they might not cover all possible strains of a virus, and therefore can have significant weaknesses when it comes to viruses that mutate frequently, like influenza or HIV.
Potential Breakthrough: Self-Assembling Peptides
One of latest advances in HPV vaccine research is the emergence of the Self-Assembling Vaccine (SAV) platform developed by Voltron Therapeutics. SAVs have been used in some form since the 1980s (the first VLP vaccine to be licensed for humans was actually the Hepatitis B vaccine). What makes the platform unique is the fact that it can use peptides (short pieces of the pathogen’s proteins) to stimulate an immune response. Preclinical trials have demonstrated very promising results in preventing HPV-related cancers—and with an excellent safety profile.
This novel SAV approach has several additional potential advantages over conventional vaccine technologies. The ability to use specific peptides allows for a more precise targeting of the immune response, potentially leading to more effective vaccines. SAV technology could also offer an advantage in terms of flexibility, as the technology can target multiple antigens by using a full protein or specific immunogenic peptides. This means it could potentially target a wider range of viruses or even different strains of the same virus—particularly beneficial for rapidly mutating viruses.
Increased stability of the SAVs may potentially negate the need for strict cold storage, simplifying transportation and distribution when compared to mRNA vaccines, for example.
Self-assembling peptides may have a simpler and more cost-effective production process compared to VLPs, as they can potentially be synthesized directly without the need for a biological host, which could also increase the scalability of vaccine production. All this could make the vaccine more accessible.
Expanding Opportunities
The SAV platform has the potential to target various types of antigens and cancers beyond HPV. Voltron has extensive plans for future research, having recently signed a Sponsored Research Agreement (SAR) with the Vaccine and Immunotherapy Center (VIC) at Massachusetts General Hospital (MGH), Harvard Medical School. The link-up intends to initiate pre-clinical trials targeting prostate stem cell antigens (PSCA) in prostate, renal cell and urothelial cancers.
According to Pat Gallagher of Voltron, “By using a full protein in our PSCA trials to target cancers of interest instead of specific peptides, we hope to demonstrate unparalleled platform flexibility that would allow us to use full protein sequences to target tumors or viruses of interest and could, in theory, allow our vaccine to induce an immune response to any specific tumor antigen of interest.”
Beyond the SAV platform, the future of immunology looks exceedingly bright, with ongoing research into Nucleic Acid-Based Vaccines, which introduce genetic material into the body with disease-specific encoded information: mRNA hit the headlines with the development of the COVID-19 vaccines by Pfizer/BioNTech and Moderna. Non-replicating Viral Vectors are also a relatively new concept, whereby a harmless virus is used as a carrier (or vector) to introduce an antigen into the body.
Other areas of research include recombinant Nanoparticles, which use elements of both the VLP and SAV techniques, and Anti-idiotype Antibodies, used to “mimic” the immune response to a wide variety of pathogens without having to include any components of the actual pathogen in the vaccine.
Investing in a Cancer–Free Future
Although HPV vaccines have seen dramatic progress in the short time since their introduction, there is still a lot of ground to make up when compared to more established immunization programs. And as no country can truly be safe from a disease if it persists elsewhere, especially in today’s age of extensive travel, broader global rates of immunization are key.
Advances in immunology, such as the development of flexible, Self-Assembling Vaccines using specific peptides, are leading to the creation of more effective, safer, and potentially less expensive vaccines. This has the potential to have a game-changing impact in less developed countries.
Continuing research and investment into HPV vaccine development is of vital importance, not just to combat cervical cancer, but to shape the landscape of oncology and infectious disease treatment for years to come.
Matthew Eitner
Matthew Eitner serves as Chief Executive Officer of Laidlaw & Company UK; a New York-based healthcare-focused investment bank. Through his expertise in equity training, Eitner successfully expands equity positions in the healthcare sector. Prior to his position at Laidlaw, Eitner served as vice president of Casimir Capital and managing director of Aegis Capital Corp.
