The COVID-19 epidemic has now entered its third year with its effects still being felt across the world. In many countries, there have been an alarming trend of waning vaccine efficacy paired with the emergence of variants with stronger immune escape and transmission ability. This consistent challenging of our pre-established immune barriers has driven the need for new, innovative vaccine modalities that overcome the hurdles of existing vaccination programs.
A recent breakthrough in COVID vaccine research is the regulatory approval of CovidenciaTM Air from CanSinoBio, a first-in-class inhaled vaccine described to ‘effectively induce comprehensive immune protection in response to SARS-CoV-2 after just one breath’. This was swiftly followed by another inhaled aerosol vaccine by Bharat Biotech in India, indicated for ‘restricted use in emergency situations.’ With these new, innovative vaccine breakthroughs, what does this mean for the future of vaccine research?
Routes of Administration: Inhalation vs Intramuscular
The advent of this new administration modality directs our attention to the comparison between inhaled vaccines and conventional intramuscular vaccines. On one hand, intramuscular vaccines are designed to stimulate the systemic immune response, triggering the production of neutralizing antibodies such as IgGs. Contrary to this, aerosolized inhaled vaccines focus on simulating respiratory viral infection, leading to increased surface-level immune response and a quicker response to viral invaders.
It is important to note that aerosol-based vaccines have been introduced previously in the form of nasal vaccines. However, questions and concerns have been raised regarding its limited efficacy in initial studies. With these new, inhaled aerosol vaccines, these vaccines have been shown to have improved biodistribution deeper into the respiratory tract in comparison to nasal vaccines.
This increased biodistribution has shown to be induce a higher immune response and confer improved protective effects in preliminary studies.
Figure 1. Mucosal immune response in the lung after vaccination through novel mRNA inhaled vaccine. 1
Evaluating the Safety and Efficacy of Inhaled Vaccines
The advantages of an inhaled vaccines are undeniable, especially logistically, where these vaccines have lower dosages, conventional storage conditions, and have a wider distribution availability. This is heavily advantageous in resource-limited countries that may struggle with establishing and distributing newer, urgent vaccines. However, the evaluation of new vaccine modalities is incomplete, especially in regulatory settings. For intramuscular COVID-19 vaccines, the standard method in predicting vaccine efficacy is through the evaluation of neutralizing-antibody levels, while cellular immunity is evaluated by antigen-specific T cell response and cytokine secretion. Conversely, the proposed efficacy of inhaled vaccines stems from the stimulation of mucosal immune response alongside humoral and cellular responses. As such, the mucosal immune response has been highlighted as a critical immune response that could play a role in combating initial infections and should be evaluated. This is evidenced by the stimulation of the mucosal immune system, triggering the production of both IgGs and local IgAs. Produced by mucosal tissue, IgAs are responsible for pathogen neutralization and prevention of binding to mucosal tissue. Thus, when combating respiratory diseases such as COVID-19, IgA levels are increasingly of-interest when evaluating vaccine efficacy.
The Next Generation of Vaccines?
Overall, it might be easy to jump to the conclusion that inhaled vaccines will be the future route of administration for vaccines. Without the need for medical professionals, needles, and lower vaccine dosages, these inhaled and other aerosol-based vaccines are undoubtedly a significant breakthrough. According to a health-analytics company in London, there are currently around 100 aerosol-based COVID-19 vaccines are being developed in the world with around 20 of them reaching human clinical trials.2
Despite the potential, conventional intramuscular vaccines are projected to retain its role as the front-line defense in vaccination. As the more mature method, intramuscular vaccines still provide strong immune responses to invading viruses. Most companies are developing inhaled vaccines as a complement or enhanced vaccine booster to improve the current state of immunity. This is supported by various studies that proposes a ‘prime-pull’ vaccination strategy which utilizes intramuscular vaccines to ‘prime’ the immune system with an inhaled booster to increase the immune defense.
Moreover, the effectiveness and potential of these inhaled vaccines needs to be further evaluated, especially as more inhaled vaccines obtain approval and widespread use. In theory, if these type of vaccines can help prevent infections and transmission, they could greatly impact the COVID-19 pandemic. Inhaled vaccines could boost a person’s “first line of defense” against the virus and have the potential to reduce onward transmission, Mike Ryan, the executive director of WHO Health Emergencies Programme, said at a press briefing. “But it remains to be seen.”
News
Advancements and clinical translation of intelligent nanodrugs for breast cancer treatment
A comprehensive review in "Biofunct. Mater." meticulously details the most recent advancements and clinical translation of intelligent nanodrugs for breast cancer treatment. This paper presents an exhaustive overview of subtype-specific nanostrategies, the clinical benefits [...]
It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome
A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection. Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate [...]
How Far Can the Body Go? Scientists Find the Ultimate Limit of Human Endurance
Even the most elite endurance athletes can’t outrun biology. A new study finds that humans hit a metabolic ceiling at about 2.5 times their resting energy burn. When ultra-runners take on races that last [...]
World’s Rivers “Overdosing” on Human Antibiotics, Study Finds
Researchers estimate that approximately 8,500 tons of antibiotics enter river systems each year after passing through the human body and wastewater treatment processes. Rivers spanning millions of kilometers across the globe are contaminated with [...]
Yale Scientists Solve a Century-Old Brain Wave Mystery
Yale scientists traced gamma brain waves to thalamus-cortex interactions. The discovery could reveal how brain rhythms shape perception and disease. For more than a century, scientists have observed rhythmic waves of synchronized neuronal activity [...]
Can introducing peanuts early prevent allergies? Real-world data confirms it helps
New evidence from a large U.S. primary care network shows that early peanut introduction, endorsed in 2015 and 2017 guidelines, was followed by a marked decline in clinician-diagnosed peanut and overall food allergies among [...]
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
Self-Organizing Light Could Transform Computing and Communications
USC engineers have demonstrated a new kind of optical device that lets light organize its own route using the principles of thermodynamics. Instead of relying on switches or digital control, the light finds its own [...]
Groundbreaking New Way of Measuring Blood Pressure Could Save Thousands of Lives
A new method that improves the accuracy of interpreting blood pressure measurements taken at the ankle could be vital for individuals who are unable to have their blood pressure measured on the arm. A newly developed [...]
Scientist tackles key roadblock for AI in drug discovery
The drug development pipeline is a costly and lengthy process. Identifying high-quality "hit" compounds—those with high potency, selectivity, and favorable metabolic properties—at the earliest stages is important for reducing cost and accelerating the path [...]
Nanoplastics with environmental coatings can sneak past the skin’s defenses
Plastic is ubiquitous in the modern world, and it's notorious for taking a long time to completely break down in the environment - if it ever does. But even without breaking down completely, plastic [...]
Chernobyl scientists discover black fungus feeding on deadly radiation
It looks pretty sinister, but it might actually be incredibly helpful When reactor number four in Chernobyl exploded, it triggered the worst nuclear disaster in history, one which the surrounding area still has not [...]
Long COVID Is Taking A Silent Toll On Mental Health, Here’s What Experts Say
Months after recovering from COVID-19, many people continue to feel unwell. They speak of exhaustion that doesn’t fade, difficulty breathing, or an unsettling mental haze. What’s becoming increasingly clear is that recovery from the [...]
Study Delivers Cancer Drugs Directly to the Tumor Nucleus
A new peptide-based nanotube treatment sneaks chemo into drug-resistant cancer cells, providing a unique workaround to one of oncology’s toughest hurdles. CiQUS researchers have developed a novel molecular strategy that allows a chemotherapy drug to [...]
Scientists Begin $14.2 Million Project To Decode the Body’s “Hidden Sixth Sense”
An NIH-supported initiative seeks to unravel how the nervous system tracks and regulates the body’s internal organs. How does your brain recognize when it’s time to take a breath, when your blood pressure has [...]
