Vaccines have changed the course of human history as we know it. Since the first vaccine was discovered in the late 1700s, vaccine technology has expanded exponentially. Deaths from diseases like polio, smallpox, measles, mumps, rubella, and diphtheria have seen a 100% reduction post-vaccination.
“The U.S. Centers for Disease Control and Prevention (CDC) estimate that U.S. children born between 1994 and 2021 who are vaccinated according to the recommended immunization schedule will prevent 472 million illnesses and 29.8 million hospitalizations over the course of their lifetimes,” observes the new Biotechnology Innovation Organization (BIO) report, The State of Innovation in Vaccines and Prophylactic Antibodies for Infectious Diseases, released January 25.
Vaccines for 34 unique pathogens have been approved in the U.S. or globally in the past decade. Yet, there is still much more work to do to prevent death and disability from infectious diseases. BIO’s report uncovers several under-resourced spots in the global vaccine pipeline.
“Our industry is working tirelessly to develop novel vaccines and antibodies for patients,” says Rachel King, President and CEO of BIO. “This work has the potential to save lives, reduce health costs, and better prepare us for future public health threats. To ensure these scientific innovations continue to advance, we must make investing in vaccine development a greater priority.”
The vaccine pipeline has breadth but not depth
Currently, the global company-sponsored clinical pipeline for infectious disease vaccines consists of 249 active novel clinical-stage programs covering 31 infectious diseases for which there is no approved vaccine, the report explains.
However, due to market issues that uniquely affect vaccines, just 10% of infectious disease threats addressed in the vaccine pipeline have 10 or more programs, explains the report. And nearly 30% of the pipeline is for COVID-19.
“Vaccines have led to a 100% reduction in the risk of death for a host of devastating diseases,” says Phyllis Arthur, BIO Senior Vice President for Infectious Diseases & Emerging Science Policy. “Yet many common infections don’t have any vaccines in clinical development. That needs to change. We need to pursue both scientific and policy changes that can help spur investment in these vital products.”
When it comes to diversifying the areas of study in vaccine development, expansion is needed. Examples of unmet need include TB, HIV, Zika, and improved flu vaccines, among others.
“HIV is an example of where the pipeline still struggles,” explains Arthur. “People have been trying to make an HIV vaccine for decades, and the science has not let us get there. Tuberculosis is similar. In many cases, the development of the science has been the challenge. And so we ask questions like, what’s it going to take for the science to discover and develop a really good TB vaccine?”
These complex questions have equally complex answers. When it comes to, for example, seasonal diseases like COVID or flu or RSV, the endemic need for vaccines is clear. But seasonal diseases, despite being the ones we think about every year, are more of an aberration than the norm.
“The pipeline is relatively deep for COVID,” David Thomas, Senior Vice President of Industry Research and Analysis at BIO and one of the report’s two lead authors. “And it’s really shallow for most everything else.”
For chronic infections like HIV or HPV, or acute diseases like malaria or TB, development happens at a different pace.
We’ve only scratched the surface of vaccine technology’s potential
Vaccines can utilize a wide range of modalities: direct antigen delivery (protein, carbohydrate, pathogen inactivation, and pathogen attenuation) and indirect antigen delivery (mRNA and viral vector-based vaccines). Since the development of the COVID vaccines, mRNA has been a large focus—understandably so, as finally understanding mRNA technology was a huge step forward. However, it is not the only technology available.
“It’s very easy for everyone to default to talking about mRNA,” explains Arthur. “It’s very important to remember that there are many more technologies out there for vaccines.”
While some diseases are bacterial, others are DNA- or RNA-based viruses and require different science and innovation. For example, while mRNA vaccine technology exists in the nucleic acid class of vaccines, vaccines for diseases like tuberculosis or cholera exist in the cell class of vaccines (using live attenuated bacteria), while the typhoid fever vaccine is in the cell class but uses inactive bacteria.
Additionally, other vaccines are of the carbohydrate class, like the pneumococcal vaccine, which uses capsid carbohydrate technology. Then there’s the better-known protein class of vaccines. This includes purified antigen protein (for diseases like Influenza, diphtheria, pertussis, tetanus, anthrax, influenza, COVID-19, and RSV), or protein-VLP (Virus-Like Particle) class vaccines (for diseases like meningococcal Group B, Shingles, hepatitis B, HPV, malaria, and COVID-19).
“There are also DNA vaccines, viral vector vaccines, self-amplifying RNA vaccines, and virus-like particle vaccines,” adds Thomas.
“There is a wide range of possibilities,” he continued, “but most haven’t had as much success as mRNA. Regardless, there are still many under development and it will come down to funding to get them past the finish line.”
These complex-sounding examples speak to one overarching truth: the pathogen kingdom is just as diverse as the animal kingdom. Profoundly different science and innovation are needed to address each disease type.
“We’ve seen incredible progress recently in areas like RSV and HPV, but unless there is more dedicated, persistent investment toward new vaccines, we’ll fall behind,” said Thomas.
Vaccine pipeline needs more venture capital investment
In the past 10 years, companies with infectious disease vaccine programs received 3.4% of the total venture capital raised for biopharmaceutical companies ($6.5 billion), explains BIO’s report. For comparison, drug development efforts for oncology received 38% of the total venture capital, 12 times as much in the same period ($72.6 billion).
Yet the oncology-vaccine investment comparison highlights an interesting tangential note when it comes to vaccine confidence.
“Innovations in vaccine development and successful vaccine candidates are only worthwhile if the population is willing to receive vaccines,” notes the report. In short, capital markets require use once a product becomes available. Meanwhile, the pandemic “had a negative impact on routine immunization for children, adolescents and adults worldwide, due to missed or delayed health services, and school and facility closures.”
Investment can come from either private investors and/or the nonprofit/public sector, depending on the studies needed. It is also important to remember the connection between investment in basic science and investment in developing innovative biotechnologies that build on that basic science.
Indeed, by partnering to solve the most pressing challenges, private, nonprofit, and public funding and investment sources can find an effective symbiosis to improve the vaccine pipeline overall.
4 recommendations for strengthening the vaccine pipeline
BIO’s report has four key recommendations to improve the vaccine development pipeline:
- capitalizing on the use of platform technologies;
- expanding access to vaccines;
- rebuilding vaccine confidence worldwide; and,
- evolving the Advisory Committee on Immunization Practices (ACIP) and National Immunization Technical Advisory Groups (NITAG) review processes.
Within the development space, the report recommends capitalizing on the use of platform technologies (e.g. analytics, database and data management, tools for application development and extension, integration, and intelligent technologies such as artificial intelligence [AI], machine learning, and the Internet of Things [IoT].)
“Platform technologies can speed development of novel approaches to improve efficacy and/or safety of vaccines, spur investment in new technologies in disease areas that have been difficult to tackle and help in pandemic preparedness,” says the report. “The policy environment must facilitate the use of platform technologies to spur investment in R&D across viral families.”
Outside of the investment space, areas of reform include expanding vaccine access, rebuilding vaccine confidence, and evolving review processes. These reforms could have a positive ripple effect across the entire healthcare market in the U.S. Ultimately, expanding the vaccine pipeline is good for the economy and healthcare costs across the board. With fewer diseases comes few pre-existing conditions and fewer chronic conditions resulting from illness, among others.
When you consider the impact of vaccines for diseases such as polio, you see that reality could be here sooner than we think. However, the health benefits and innovation resulting from such breakthroughs are undeniable when it comes to the future of human health.
