FAPESP Agency – A vaccine in the form of an easy-to-apply, low-cost nasal spray, long-lasting protection even against variants and capable of blocking the action of the new coronavirus even in the nose, where infections begin. This is the objective of a project being developed by a group of researchers from the University of São Paulo (USP), in partnership with the Federal University of São Paulo (Unifesp) and the Oswaldo Cruz Foundation (Fiocruz).
The new immunizing agent, still in the early stages of study, was presented on Monday (30/8) during the ILP-FAPESP Science and Innovation Cycle. The event, a partnership between FAPESP (Research Support Foundation of the State of São Paulo) and the São Paulo Legislative Institute (ILP), is available in full on YouTube.
“One of the advantages of nasal immunization is that it generates local immunity in the nose, in the oropharynx [parte da garganta logo atrás da boca] and in the lungs. It is exactly the ideal ‘territory’ to prevent the consolidation of a SARS-CoV-2 infection. Injectable vaccines are very good for inducing systemic immunity and also in the lungs, but they are not especially good for generating a protective response in the nasal and oropharynx region”, he explained. Edécio Cunha Neto, professor at the Faculty of Medicine (FM-USP) and researcher at the Immunology Laboratory of the Instituto do Coração (InCor).
The project, of which he is one of the main researchers, has support FAPESP and is coordinated by Jorge Elias Kalil Filho, professor at FM-USP and head of the Laboratory of Clinical Immunology and Allergy at Hospital das Clínicas (HC-FM-USP).
“The vaccines that exist today are excellent, developed in record time, but now we need a second-generation immunizer capable of overcoming problems that arose during the course of the immunization [escape imune ou efeitos adversos, por exemplo] and serve as a reinforcement for injectables,” said Cunha Neto.
According to the researcher, the goal is to create a vaccine that generates long-lasting neutralizing antibodies and also robustly stimulates cellular immunity – that mediated by T lymphocytes, which recognize the pathogen and destroy infected cells.
In addition, the new vaccine should protect against strains of concern. For this, researchers are developing an antigen that may contain the protein S region (spike, present on the surface of the virus) that binds to human cells (RBD) of three or four variants at the same time.
The antigen will also contain pieces of proteins that stimulate the cellular response, longer than that mediated by neutralizing antibodies. Therefore, it should include the so-called cytotoxic CD8+ T lymphocytes, which kill infected cells, and the CD4+ T lymphocytes, which help in antibody production and cytotoxic responses.
Currently, the team is testing 25 different combinations of proteins, which will be encapsulated in ceramic nanoparticles covered with a polymer to guarantee the adhesion of the immunizing agent to the nasal environment.
Preliminary tests with two doses of prototype antigens led to the generation of high amounts of neutralizing antibodies in mice. Cunha Neto emphasizes that the expected product should still be stable at room temperature, in addition to being safe, with low cost and mastery of the entire manufacturing process in the country.
The expectation is that clinical trials will be carried out in 2022.
To know which variants should be targeted by a vaccine, it is essential to know which strains are most present in the country. For this, some groups in Brazil carry out the so-called genomic surveillance. The work consists of sequencing the genome of the variants in circulation to determine those that are of most concern in epidemiological terms.
In partnership with the City of São Paulo, the Joint Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE), supported by FAPESP, is monitoring the prevalence of the delta variant of SARS-CoV-2 in the municipality.
“In the beginning, the proportion of this strain was 2%, but it has been systematically rising and spreading in various parts of the city of São Paulo. Today we are around 33%. Unfortunately, the delta will predominate in the coming weeks,” he said. Esther Sabino, professor at FM-USP and researcher at the Institute of Tropical Medicine (IMT-USP).
Another speaker was Fernando Spilk, dean of research at the Feevale University and coordinator of the Corona-Ômica Network of the Ministry of Science, Technology and Innovation (MCTI), created in 2020 to lead genomic surveillance efforts in the country. Among other issues, the researcher spoke of efforts to integrate data from across the national territory.
Sandra Vessoni, director of the Scientific Development Center of the Butantan Institute and coordinator of the SARS-CoV-2 Variant Alert Network of the State of São Paulo, spoke about the monitoring, diagnosis and definition of the vaccine strategy carried out by the institution.
Paola Cristina Resende Silva, researcher at the Respiratory and Measles Virus Laboratory at Instituto Oswaldo Cruz/Fiocruz, coordinator of the curator team for the GISAID data platform in Brazil, explained how the work in the repository, which gathers variant sequencing data, is carried out from around the world.
The meeting was mediated by Carlos Américo Pacheco, director-president of FAPESP’s Technical-Administrative Council.
Governo do Estado de São Paulo