Nanoparticles increase the effectiveness of vaccines
Many viruses and bacteria enter the human body through the mucous membranes lining the respiratory tract, the inner surface of the lungs, the digestive tract and the genital tract. Scientists are actively working on creating vaccines that could protect the mucous membranes from pathogens.
Vaccines can be injected into the lungs by aerosol spray, but the lungs often remove such drugs before they can cause the formation of an immune response. Researchers at the Massachusetts Institute of Technology have developed a method to overcome this problem using nanoparticles that allow the vaccine to be stored for a long time not only on the mucous membrane of the lungs, but also on the mucous membranes located at a distance from the place of administration of the drug, for example in the digestive tract.
According to the head of the study, Professor Darrell Irvine, such vaccines can help in the fight against the influenza virus and other viruses that are pathways to the respiratory tract, sexually transmitted infections, herpes simplex virus and papillomavirus, and possibly cancer.
As a carrier for protein antigens, which are the active ingredient of the vaccine, the authors proposed using nanoparticles developed by them 2 years ago, consisting of several layers of lipid molecules. The chemical bonds between the lipid layers ensure the stability of such nanoparticles, which, when they enter the lungs, are absorbed and digested by macrophages. The protein antigens of the vaccine encapsulated between the lipid layers are also processed by macrophages and presented to T-lymphocytes. Activation of the latter is the main mechanism for the formation of a pathogen-specific immune response.
Image of nanoparticles used as a carrier for vaccines,
obtained using a cryo-electron microscope.Experiments on mice have shown that HIV antigens and tumor antigens encapsulated in nanoparticles are more effectively absorbed by immune cells than pure antigens injected into the lungs or under the skin.
Mice are immune to HIV, therefore, to test the effectiveness of the emerging immune response, they were infected with a genetically modified cowpox virus encoding the HIV protein against which an experimental vaccine was directed.
The cowpox virus usually penetrates the ovarian tissue quickly, but it turned out that vaccination completely prevented this process. Vaccinated animals lost a little weight after infection, but soon fully recovered. At the same time, the infection was 100% fatal for mice of the control group, in whose ovaries high concentrations of viral particles were detected.
The study of the immune status of animals of the experimental group demonstrated the presence of a large number of T-lymphocytes on the mucous membranes removed from the site of vaccine administration, known as "memory cells" and providing long-term immunity against the disease.
According to the authors, additional studies are needed to clarify the possibility of using nanovaccines for humans, however, the proposed strategy may be particularly effective in combating diseases that require the expressed participation of T-lymphocytes in the immune response, such as HIV.
To assess the suitability of the developed approach as an antitumor therapy, the researchers implanted modified melanoma cells synthesizing ovalbumin egg protein into mice. Three days later, the animals were injected with a vaccine against ovalbumin, which led to the complete disappearance of tumors in animals that received the nanovaccine. In the control group animals that were injected with the usual version of the vaccine, the tumors progressed.
In the near future, the researchers plan to conduct similar experiments on more complex tumor models using vaccines specific to proteins expressed by cancer cells.
Article by Adrienne V. Li et al. Generation of Effector Memory T Cell–Based Mucosal and Systemic Immunity with Pulmonary Nanoparticle Vaccination is published in the journal Science Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on MIT materials: Nanoparticle vaccine offers better protection.
30.09.2013