Production scaling phase began at Unicamp and human trials are expected to begin in early 2021
Scientists from USP and Unicamp are developing a nasal spray vaccine against Covid-19. The vaccine has several advantages over the injectable method, including direct action on the nasal mucosa, which is one of the main entry points for the new coronavirus into the human body. In this way, the prospect is that the virus will be eliminated in the entry channel. The vaccine is in the pre-clinical testing phase, in mice, and is moving to the production scaling stage, carried out at Unicamp.
The scaling of production, according to professor Laura de Oliveira Nascimento, from the Faculty of Pharmaceutical Sciences (FCF) at Unicamp, who heads this process, is the moment in which we seek to test whether the vaccine, developed on a laboratory scale, can be produced in larger scale, a process that is essential for a vaccine intended to be launched commercially. “Today there are several effective vaccine formulations published and on a laboratory scale. But we know that scaling is not always viable and for this reason several vaccines are not commercialized, as they are not scalable”, he explains.
The conception of the USP and Unicamp vaccine, says Laura, from the beginning, incorporated the concern with a formulation that could be applicable to the population. For the researcher, the experience of the team leader, USP professor Marco Antonio Stephano, was fundamental in the design of industrial production. “From the beginning, he and the team have been producing a formulation that can be produced quickly and on a large scale,” she notes.
The challenge at this stage of scaling, according to the professor, is to maintain the physicochemical characteristics of the vaccine, which uses a formulation based on nanostructured polymers, that is, which have a specific size range on the nanometer scale. “For this to continue both at 10 ml, which is when we do a laboratory scale to test on mice, and at 10 liters, so that the physical-chemical characteristics of this vaccine can be maintained, it is necessary to study the scale. And that’s what the Unicamp team will help with: ensuring that this vaccine can be produced in greater quantities, maintaining the quality that Professor Marco developed on a laboratory scale,” she explains.
Applied technologies and vaccine production stages
The immunologist and professor at the Faculty of Pharmaceutical Sciences at USP, Marco Antonio Stephano, coordinates the team responsible for formulating the vaccine and punctuates the steps in the development of the vaccine. The first step was the production of the antigen, which in this case is a protein molecule that stimulates the immune system to fight the virus. Afterwards, the production of this substance is scaled up, so that it is possible to develop the vaccine.
To increase the delivery of the formula's antigens to the mucosa, researchers use nanotechnology. “With nanotechnology we are able to increase the concentration of antigens associated with carrier particles, because when you reduce the diameter of a circle, you increase the proportion of surface area in relation to the volume of that particle and the number of particles with the same amount of polymer . So you end up increasing the total surface area that the antigen can associate with and be exposed to the organism”, says Marco Antonio.
Furthermore, as the polymer (molecule that makes up the antigen) used is mucoadherent, it stays on the nasal mucous membranes for a long enough time, causing the cells to take it to the immune system and stimulate it to produce two types of antibodies against the virus. new coronavirus. “This muco-adherent property of the polymer means that it remains deposited on the mucosa for two or three hours, which is enough for macrophages and specialized cells to capture these antigens. Once captured, they are processed, go to the immune system and produce two types of antibodies: IgG, which remains in the blood circulation, and secretory IgA, which remains on the mucosa”, he explains.
Advantages of the nasal spray vaccine
One of the advantages of the spray vaccine, when compared to injectable vaccines, is precisely the fact that they also stimulate the production of secretory IgA. In this way, the main means of entry of the virus into the body is protected: the mucous membranes of the airways. According to a recent study regarding the production of another vaccine using a nasal spray, it was seen that this method eliminates viral RNA in the nose, which was not observed with the injectable vaccine.
Thus, although both vaccines in this study are protective, according to Professor Laura, the nasal spray vaccine had the advantage of completely eliminating the virus, and already at the gateway. “This advantage of protecting the person from viral entry has been demonstrated, so you can have immunity in the nasal mucosa, which prevents viral entry and a possible short-term residence of the virus, inhibiting contamination of other people.”
The researcher also notes that the spray vaccine is easier to apply, requiring no specific training. As it does not require a needle, it also solves possible material supply problems. “They have already made calculations that if everyone had to be vaccinated at the same time, there would not be a needle to provide for all of us, so we have this advantage”, she says.
She also highlights the fact that it is an innovative vaccine, economically viable and made with 100% Brazilian technology, reducing dependence on institutions from other countries. Finally, notes Laura, many people are afraid of injectable injections. Thus, when administered via the nasal route, there is greater adherence to vaccination.
Perspectives for the vaccine
One of the main concerns in the context of the pandemic is the race to make a vaccine available. In the case of the nasal spray vaccine, the professors explain that pre-clinical trials, those carried out on animals, must be repeated in October. The perspective is that by the end of November the results will be submitted to the Research Ethics Committee, so that clinical trials on humans can then be approved and begin in January or February.
With the clinical results, it is up to the National Health Surveillance Agency (Anvisa) to determine whether the vaccine is of quality and whether laboratories have the technical conditions to formulate and produce it. "This happens for any vaccine, be it those that are arriving in stage 3, or ours that is being developed. Anvisa is the body that protects the consumer, not the industry or the university, so it is very important to have this safety”, remember Marco Antonio.
After testing on humans, the idea is that the technology will be supported by a company with large-scale production capacity. To achieve this, the group studies critical production parameters. “We want the company to actually be able to produce and this work not simply become another article, as we have many articles about vaccines, which are important to have a scientific basis, but which have not become a product that can help the population”, assesses the researcher.
Despite the perspectives, they emphasize that they depend on a series of factors and mainly on what the immunological response will be like in animal tests. “It all depends on the tests. If the tests quickly give us a positive answer, the schedule will be easily followed”, emphasizes Professor Laura.
Also check out the full interview with professors Marco Antonio Stephano and Laura de Oliveira Nascimento on podcast (click to access).