In 1955 Jonas Salk developed and debuted the inactivated polio vaccine. Within five years, cases of polio in the United States dropped dramatically, and vaccination of children against infectious diseases like polio became the new standard of care.
The Salk vaccine heralded a new dawn in the 1960s for the treatment of infectious diseases, particularly severe respiratory syncytial virus (RSV) infections in children. However, when a formalin-inactivated version of a RSV virus vaccine similar to the polio vaccine was tested in 1967, many immunized infants actually experienced an exacerbated form of RSV disease – including high fever, bronchopneumonia, and wheezing – than they did later wild-type or naturally occurring RSV viruses circulating in the community were infected.
This so-called exacerbated respiratory disease or increased RSV disease (ERD) resulted in increased hospitalization rates in vaccinated children and two deaths. The vaccine has been postponed and vaccine preparations inactivated with formalin have largely fallen out of favor. Other, more advanced polio vaccines designed to complement the original Salk vaccine have also failed, causing oral polio vaccine viruses to revert to wild-type and become virulent again.
Although polio is now largely eradicated, these examples remind us that campaigns for the common good are often at the expense of individual harm and that clinical progress cannot be viewed as an exact or even linear process. Negative results are not necessarily predictable from previous experiments, and clinical studies cannot be fully relied on as evidence of adverse events with a low incidence. New clinical models such as B. Human Challenge studies, can be deployed where clinical studies stop and enable the rapid development of prognostic efficacy data for many infectious diseases.
HOW TO LOSE BOTTLE VACCINE CANDIDATES – EVEN PROMISING
It’s no secret that the healthcare industry is suffering from innovation bottlenecks. Three examples from recent medical history illustrate this point:
- Despite almost 40 years of research, there is no vaccine against HIV. Patients can be treated with antiretroviral drugs, which have been shown to be remarkably effective and have dramatically improved the life expectancy of those affected. However, an easy-to-administer vaccine must replace those expensive “drug cocktails” that patients must take for the rest of their lives.
- The global overprescription of antibiotics has led to resistance in almost all types of bacteria, and new alternatives still need to be developed. Up to 60 percent of pathogens Escherichia coli is now resistant to the best broad spectrum antibiotics; In the case of urinary tract infections, the number increases to 93 percent. Meanwhile, the loads are heavier Streptococcus pyogenes Bacteria that cause scarlet fever have been found in Hong Kong and the UK. So far, no alternatives to these antibiotics have been developed.
- In the early and critical days of treating patients with COVID-19, hospitals in Italy, New York City, and around the world were forced to operate the mechanical ventilator – a device that was invented nearly 100 years ago and has been running since the mid-20th century Century remained practically unchanged – only one patient at a time. This forced the hospitals to ration, which contributed to an increased death rate.
These bottlenecks do not result from an unwillingness to address the problem. After all, we now have a polio vaccine, a smallpox vaccine, and several COVID-19 vaccines. Even without “final steps” like HIV vaccines or more effective antibiotics, antiviral drugs have dramatically improved the life expectancy and quality of life of patients with HIV and AIDS, while antibiotics can, in most cases, prevent the main complications of scarlet fever.
There is clearly a will to innovate. Rather, bottlenecks are the result of a paradigm shift in the development process, when a positive result quickly becomes negative or progress suddenly comes to a standstill. An idea that looks good on paper is too difficult to realize.
Many scenarios can lead to an innovation bottleneck in vaccine development. Drug toxicity, vaccine ineffectiveness, or patient side effects can be easily identified. The complexity of the design can prevent the drug dose from being delivered or add to an expensive manufacturing process. Additional barriers can include limited access to raw materials, poor stability, or cold chain requirements – as we saw with Pfizer’s COVID-19 vaccine.
Even if all the right criteria are met, the most promising therapy or vaccine can still fall out of favor. A competitor can make an equally effective product that can be manufactured at a lower cost, more easily administered, or used in a broader population such as the very young, the elderly, or in immunocompromised populations. While it is too early to judge right now, this may be the case with the one-dose COVID-19 vaccine from Johnson & Johnson versus the two-dose vaccines from AstraZeneca and Moderna, which also adds to the added challenges of the Scheduling of follow-up appointments entails and clinical records.
HOW HUMAN CHALLENGE CAN ACCELERATE VACCINE DEVELOPMENT
The most common bottlenecks in vaccine development are cost, risk, safety, and time. A vaccine may show promise in a preclinical or Phase I trial, but if any of these factors work against a research team, a sudden paradigm shift may not advance the candidate.
Fortunately, clinical models such as human challenge trials offer the opportunity to overcome these bottlenecks. In these studies, healthy volunteer participants are deliberately challenged or infected with an infectious disease. This allows researchers to study the effect of vaccination on the disease itself in a controlled environment. Participants stay on-site for the duration of the study, and a fully staffed analytical laboratory can provide priority access to any care participants who need them. In such a model, almost all experimental parameters can be controlled (the means of challenge for which the subjects are examined, the assessment plan, the dose of the infectious agents administered and the time of inoculation).
Human challenge studies provide more valuable information than animal challenge studies, which provide results that need to be extrapolated to determine the effects on humans. They also allow studies with a small pool of participants with minimal risk of adverse outcomes, clinical complications, or hospitalization. Finally, the small size of the study reduces the financial risk of failure because a human challenge study requires much less vaccine than a phase II clinical study.
It is important to note that human challenge studies are not conducted in isolation. The current clinical trial system, backed by decades of successful drug and vaccine development, could be said to be practically a quality control system. The aim of the clinical trial is to fail the poor candidates as well as to drive the most promising ones forward. Biotechnology and pharmaceutical companies must obtain statistically significant data from highly regulated and vetted studies before a product is approved for marketing. All steps in this process have high quality gateways.
Rather, the role of the Human Challenge study is to act as a gateway to promising vaccines once basic, preclinical, and Phase I studies have provided initial validation of the candidate’s safety. It’s also a proven track record that has resulted in safe, effective, and inexpensive vaccine solutions for almost all infectious diseases in children, as well as for malaria, typhoid, cholera, and flu. These advances in medicine have moved life expectancy forward 10 years since the 1960s – and have the potential to help the average person live into the 90s by 2050.
COVID SHOWS WHY ACCELERATE VACCINE DEVELOPMENT IS A MATTER
Efforts to develop a vaccine against the COVID-19 pandemic are a clear example of the importance of removing barriers to innovation in healthcare.
At the height of vaccine development, there were at least 120 vaccines in the pipeline. A small number of now outdated vaccine candidates have caused exacerbated respiratory illnesses, severe acute lung injuries, and other types of organ damage. Experience has shown that only about 6 percent of all COVID-19 vaccine candidates will ultimately make it to market.
Given these risks, the industry was cautious about the COVID-19 vaccine development process, similar to what has been the case with countless development projects in the past. At the same time, the need for a vaccine was acute; SARS-CoV-2 has been predicted to cut the average lifespan in the UK by up to six years. A schedule similar to that for an HIV vaccine would simply not be acceptable.
In this context, there was a fundamental change to the FDA and WHO guidelines for the development of a COVID-19 vaccine. Regulators have created environments where vaccines can move into late-stage studies that focus on solid safety signals via markers of efficacy. This new way of looking at things makes it possible to rapidly develop safe products while realizing that a high rate of wear can be expected while unexpected events should not be treated as exceptional. The focus was not on the setbacks that should halt vaccine development as a whole, but on the advances that give rise to further development.
In this environment, established trading companies in the human challenge testing market, including hVIVO, can pioneer epidemic and pandemic modeling to accelerate the development of vaccines with proven efficacy. These companies can serve as valuable partners for the pharmaceutical and biotech industries by removing longstanding innovation bottlenecks.
By studying the effects of the vaccine in subjects known to have the disease the vaccine is targeting, researchers can screen potential vaccine candidates in a timely manner and move the most promising candidates to larger studies faster than the traditional clinical trial model . This allows more people to receive “puffs in the arms” in less time, which can reduce the spread of a deadly disease and improve health outcomes around the world.