A deep breath instead of an injection: Researchers have developed a new vaccination process against infections caused by Sars-CoV-2 and Co. that is based on the inhalation of a dry powder. It consists of antigen-carrying microcapsules that can penetrate deep into the lungs. The advantage of the system is that, in contrast to injectable vaccines, immunity is specifically provided in the respiratory tract, through which infections primarily occur. The dry vaccine can also be stored unrefrigerated. Initial tests of the system on animals have yielded promising results, the researchers report.
Acute pressure to succeed has become a strong driving force in medical research: The Covid-19 pandemic has led to the development of new vaccination technologies. Several types of Sars-CoV-2 vaccines have proven to be successful in reducing the risk of infection or in mitigating the potential danger of Covid-19 disease. What they have in common is the method of administration: vaccination is done through an intramuscular injection, which leads to an immunization reaction in the body. But there is a catch: the intramuscular vaccinations do not generate a local immune reaction in the body that also extends into the respiratory tract. The vaccination protection therefore does not work where the infection process usually begins when someone is infected with the pathogens.
Targeted immunization of the respiratory tract
For this reason, vaccines are currently being developed that can be administered via the respiratory tract so that immunity can also be specifically triggered there. So far these have been concepts based on the inhalation of nebulized liquids containing the vaccine - for example via nasal spray. However, there are limitations to effectiveness and, above all, there remains a disadvantage that also applies to injectable vaccines: liquid formulations can only be kept for longer if they are constantly cooled. This makes storing and transporting the vaccines expensive and time-consuming. This can be a significant problem, especially when supplying regions with weak infrastructure. The international research team led by Tong Ye from the Chinese Academy of Sciences in Beijing has now developed a vaccination technology that enables immunization including the respiratory tract and does not require cooling.
The concept is based on a powdered vaccine substance that consists of four micrometer-sized beads made of a biodegradable material. These spheres are in turn equipped with protein nanoparticles, which represent the actual vaccine. It is a fusion of a bacterial protein with a specific structural element of the Covid-19 pathogen: The coronavirus spike protein of Sars-CoV-2 acts as an antigen to which the body's immune system reacts by forming antibodies. After laboratory production, the researchers used a freeze-drying method to convert the vaccine substance into a dry powder form. Research has shown that the vaccine remains stable in this state at room temperature for at least a month.
Finely atomized, the vaccine can then be inhaled using an inhaler. Due to the small size of the microcapsules, they can reach deep into the lungs and be deposited. They then slowly dissolve there and release their cargo. This ensures a particularly long-lasting presentation of the Sars-CoV-2 spike fragments. This means that the immune cells in the lungs react particularly intensively to the antigen. In addition to systemic immunization via the blood, there is also a targeted vaccination effect in the lungs: antibodies against the pathogen are formed in the mucous membrane, the scientists explain.
Promising test results
The team has already demonstrated through initial animal experiments that their system actually delivers what it promises: Mice, hamsters and macaques were treated with the powder vaccine through inhalation. The subsequent studies showed that this led to sustained immunization of the animals, which protected against Sars-CoV-2 infection. In addition to the antibodies in the blood, the researchers were also able to detect the antibodies in the respiratory tract mucosa. “The vaccine induced strong production of immunoglobulin G and immunoglobulin A, as well as a local immune cell response, which together ensured effective protection against Sars-CoV-2 in the mice, hamsters and non-human primates,” the scientists write.
They were also able to document that the system is suitable for more complex immunization: the nanoparticles contained in the microspheres can be loaded with several antigens at the same time, which can trigger an immune response that can provide broad vaccination protection against different versions of the pathogen. The system is also not limited to use against coronaviruses: Due to the flexibility of antigen presentation, it also enables the rapid and convenient development of other respiratory virus vaccines, the scientists say.
According to them, thanks to these advantages, there is now significant potential for their inhalable dry vaccine. Before the concept can be used in the fight against Covid-19 and other respiratory diseases, further development work is necessary. First of all, it must now be proven that the vaccine substance does not lead to any problematic effects in the lungs when inhaling deeply, even in sensitive people.
Source: Chinese Academy of Sciences, specialist article: Nature doi: 10.1038/s41586-023-06809-8