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
Nanoparticle-Based Vaccine Shows Promise in Fighting Cancer
In a study published in OncoImmunology, researchers from the German Cancer Research Center and Heidelberg University have created a therapeutic vaccine that mobilizes the immune system to target cancer cells. The researchers demonstrated that virus peptides combined [...]
Quantitative imaging method reveals how cells rapidly sort and transport lipids
Lipids are difficult to detect with light microscopy. Using a new chemical labeling strategy, a Dresden-based team led by André Nadler at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and [...]
Ancient DNA reveals cause of world’s first recorded pandemic
Scientists have confirmed that the Justinian Plague, the world’s first recorded pandemic, was caused by Yersinia pestis, the same bacterium behind the Black Death. Dating back some 1,500 years and long described in historical texts but [...]
“AI Is Not Intelligent at All” – Expert Warns of Worldwide Threat to Human Dignity
Opaque AI systems risk undermining human rights and dignity. Global cooperation is needed to ensure protection. The rise of artificial intelligence (AI) has changed how people interact, but it also poses a global risk to human [...]
Nanomotors: Where Are They Now?
First introduced in 2004, nanomotors have steadily advanced from a scientific curiosity to a practical technology with wide-ranging applications. This article explores the key developments, recent innovations, and major uses of nanomotors today. A [...]
Study Finds 95% of Tested Beers Contain Toxic “Forever Chemicals”
Researchers found PFAS in 95% of tested beers, with the highest levels linked to contaminated local water sources. Per- and polyfluoroalkyl substances (PFAS), better known as forever chemicals, are gaining notoriety for their ability [...]
Long COVID Symptoms Are Closer To A Stroke Or Parkinson’s Disease Than Fatigue
When most people get sick with COVID-19 today, they think of it as a brief illness, similar to a cold. However, for a large number of people, the illness doesn't end there. The World [...]
The world’s first AI Hospital, developed in China is transforming healthcare
Artificial Intelligence and its developments have had a revolutionary impact on society, and healthcare is not an exception. China has made massive strides in AI integrated healthcare, and continues to do so as AI [...]
Scientists Rewire Immune Cells To Supercharge Cancer-Fighting Power
Blocking a single protein boosts T cell metabolism and tumor-fighting strength. The discovery could lead to next-generation cancer immunotherapies. Scientists have identified a strategy to greatly enhance the cancer-fighting abilities of the immune system’s [...]
Scientists Discover 20 Percent of Human DNA Comes from a Mysterious Ancestor
Humans carry a complex genetic history that continues to reveal surprises. Scientists have found that 20% of our DNA may come from a mysterious ancestor, according to WP Tech. This discovery changes how we understand [...]
AI detects early prostate cancer missed by pathologists
Men assessed as healthy after a pathologist analyses their tissue sample may still have an early form of prostate cancer. Using AI, researchers at Uppsala University have been able to find subtle tissue changes [...]
The Rare Mutation That Makes People Immune to Viruses
Some people carry a rare mutation that makes them resistant to viruses. Now scientists have copied that effect with an experimental mRNA therapy that stopped both flu and COVID in animal trials — raising [...]
Nanopore technique for measuring DNA damage could improve cancer therapy and radiological emergency response
Scientists at the National Institute of Standards and Technology (NIST) have developed a new technology for measuring how radiation damages DNA molecules. This novel technique, which passes DNA through tiny openings called nanopores, detects [...]
AI Tool Shows Exactly When Genes Turn On and Off
Summary: Researchers have developed an AI-powered tool called chronODE that models how genes turn on and off during brain development. By combining mathematics, machine learning, and genomic data, the method identifies exact “switching points” that [...]
Your brain could get bigger – not smaller – as you age
recently asked myself if I’ll still have a healthy brain as I get older. I hold a professorship at a neurology department. Nevertheless, it is difficult for me to judge if a particular brain, [...]
Hidden Cost of Smart AI: 50× More CO₂ for a Single Question
Every time we ask an AI a question, it doesn’t just return an answer—it also burns energy and emits carbon dioxide. German researchers found that some “thinking” AI models, which generate long, step-by-step reasoning [...]