A vaccine in the form of an easy-to-use, inexpensive nasal spray that also provides long-term protection against variants and is able to block the effects of the new coronavirus in the nose, where infections begin.
This is the goal of a project being developed by a research group from the USP (University of São Paulo) in collaboration with Unifesp (Federal University of São Paulo) and Fiocruz (Oswaldo Cruz Foundation).
The new immunization agent, which is still in the early stages of the study, was presented on Monday (08/30) as part of the ILP-FAPESP science and innovation cycle. The event, a partnership between FAPESP and the ILP (Institute of Legislative Paulista) is fully available on YouTube.
“One of the advantages of nasal immunization is that it creates local immunity in the nose, in the oropharynx [parte da garganta logo atrás da boca] and in the lungs. It is exactly the ideal “area” to prevent the consolidation of a SARS-CoV-2 infection. Injectable vaccines are very well suited to induce systemic immunity and also in the lungs, but they are not particularly good at creating a protective reaction in the nasal and oropharyngeal areas, “explains Edécio Cunha Neto, professor at the FM USP (Faculty of Medicine) and research assistant at the Immunology Laboratory of the InCor (Heart Institute).
The project, in which he is one of the main researchers, is supported by FAPESP and by Jorge Elias Kalil Filho, professor at FM-USP and head of the HC-FM-USP-1; Clinical immunology and allergy laboratory in the Hospital das Clínicas.
“The vaccines that exist today are excellent and have been developed in record time, but what we need now is a second generation immunizer that is capable of overcoming the problems encountered during immunization.” [escape imune ou efeitos adversos, por exemplo] and serve as reinforcement for injectables, “said Cunha Neto.
The researcher’s goal is to develop a vaccine that generates long-lasting neutralizing antibodies and also strongly stimulates cellular immunity – mediated by T lymphocytes, which recognize the pathogen and destroy infected cells.
In addition, the new vaccine is said to protect against strains of concern. To do this, the researchers are developing an antigen that can contain the region of the protein S (spike, present on the surface of the virus), which simultaneously binds to human cells (RBD) of three or four variants.
The antigen also contains pieces of protein that stimulate the cellular response for longer than that mediated by neutralizing antibodies. Therefore, it should include the so-called CD8 + cytotoxic T lymphocytes, which kill infected cells, and the CD4 + T lymphocytes, which aid in antibody production and cytotoxic reactions.
The team is currently testing 25 different combinations of proteins encapsulated in ceramic nanoparticles covered with a polymer to ensure the immunization agent adheres to the nasal environment.
Preliminary tests with two doses of prototype antigens produced high levels of neutralizing antibodies in mice. Cunha Neto emphasizes that the expected product should still be stable at room temperature, in addition to its safety, low cost and mastery of the entire manufacturing process in the country.
Clinical studies are expected to be conducted in 2022.
Genome monitoring
In order to know which variants a vaccine should target, it is important to know which strains are most common in the country. For this purpose, some groups in Brazil carry out what is known as genome monitoring. The work is to sequence the genome of the variants in circulation to identify those that are of most epidemiological concern.
In partnership with the city of São Paulo, the FAPESP-supported Joint Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) is monitoring the prevalence of the delta variant of SARS-CoV-2 in the city. .
“Initially the percentage of this variety was 2%, but it has grown systematically and spread to different parts of São Paulo. Today we are at around 33%. Unfortunately, the delta will predominate in the coming weeks, “he said Ester Sabino, professor at FM-USP and researcher at IMT-USP (Institute for Tropical Medicine).
Another speaker was Fernando Spilki, Dean of Research at Universidade Feevale and coordinator of the Corona-Ômica network of MCTI (Ministry of Science, Technology and Innovation) established in 2020 to lead genome surveillance efforts in the country. Among other things, the researcher spoke of efforts to integrate data from across the country.
Sandra Vessoni, director of the Scientific Development Center at the Butantan Institute and coordinator of the SARS-CoV-2 Variant Alert Network in the state of São Paulo, spoke about monitoring, diagnosing and defining the vaccine strategy implemented by the institution.
Paola Cristina Resende Silva, researcher at the Respiratory and Measles Virus Laboratory at the Instituto Oswaldo Cruz / Fiocruz, coordinator of the team of curators of the GISAID data platform in Brazil, explained how the work in the repository that collects data on variant sequencing is carried out from around the world.
The meeting, mediated by Carlos Américo Pacheco, Director-President of the Technical-Administrative Council of FAPESP, was also attended by Karina do Carmo, President of ILP, and Deputy Patricia Bezerra, President of the ALESP Health Commission.