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USP-partnered Covid vaccine shows promising results in new phase
The vaccine proved safe and effective at the end of the second phase of clinical trials, but it still needs to be tested on a larger number of volunteers; trials are coordinated by CT-Vacinas, in Minas Gerais
Vaccine developed with the participation of USP may protect against different variants of SARS-CoV-2 – Photo: Freepik
Researchers at the Biotechnology Research Center CT-Vacinas in Minas Gerais recently completed the phase 2 clinical trials of a Covid-19 vaccine with promising results. Tested on 319 volunteers over 12 months, the vaccine, developed in partnership with USP, proved safe and effective against different variants of SARS-CoV-2. Scientists are now awaiting approval from the National Health Surveillance Agency (Anvisa) to begin the third phase of human testing, which will be carried out on around 5,000 participants. The goal is to confirm the preliminary evidence gathered in previous trials.
SpiN-Tec, as it was called, began to be conceived in 2020, when immunologist Julia Teixeira de Castro began her doctorate at USP’s Ribeirão Preto Medical School (FMRP). Initially, Julia was working on developing a vaccine against Chagas disease, but due to the increase in Covid-19 cases, her efforts were redirected. From there, the researcher worked on creating a fully national vaccine that would offer protection regardless of the emergence of new variants. The research was carried out under the supervision of Ricardo Gazzinelli, associate professor at FMRP and coordinator of CT-Vacinas (linked to the Federal University of Minas Gerais and the Oswaldo Cruz Foundation – Minas).
“What we did was design a vaccine that primarily induces cellular immunity – an immune response capable of recognizing regions of the virus even after new mutations emerge,” Julia explains to Jornal da USP. This recombinant protein vaccine triggers a response mediated by T lymphocytes, a type of immune cell that acts against intracellular invaders such as viruses.
The chimeric protein contains the sequences of the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2. “This is the first time that a vaccine fully developed in Brazil has reached this stage,” celebrates Julia.
Gazzinelli emphasizes that, in addition to having Brazilian technology, SpiN-Tec is a vaccine with low production costs. “It has been shown to have stability for 24 months at 4ºC, meaning it can be kept in a standard refrigerator.”
Evidence-based choice
Most vaccines currently available are based solely on the spike (S) protein – an important component of the virus that acts as a “key” to enter human cells and replicate – and the generation of neutralizing antibodies, responsible for inactivating the virus that infects the body. But as the pandemic progressed, surveillance experts began observing different mutations related to the spike that increased the rate of virus transmission and caused these antibodies to escape from vaccines and medications.
“At the beginning of the pandemic, the vaccines worked very well, providing a level of protection that reached 90%. But, with the emergence of variants, this effectiveness has been falling and today it is around 40%”, explains Gazzinelli.
Meanwhile, studies indicated that the nucleocapsid (N) protein remained virtually unchanged over time and that it could be a target for the development of a vaccine that would produce robust immunity.
To confirm the hypotheses, the first phase of the work involved in silico studies – with computer simulations. This type of analysis groups, interprets and understands information using tools from biology, mathematics, computing, and related areas.
Julia conducted an epitope prediction study – a technique in which algorithms analyze protein structures to identify regions most likely to interact with the immune system. “To design the protein, we used this approach and confirmed that we had two strong targets: the S and N proteins”, she explains. “We then combined regions of these proteins into a single sequence and produced it at a laboratory scale, in small quantities, to start testing.”
In in vitro tests, peripheral blood samples from patients immunized with Coronavac or convalescents were collected and scientists found that the SpiN protein, used in SpiN-Tec, was recognized by memory T lymphocytes.
Hamsters and mice received two doses of the vaccine 21 days apart and were then infected with SARS-CoV-2. Hamsters immunized with Spin showed high production of IgA and IgG, two types of antibodies produced by the immune system to fight infections. In protected mice, the formulation proved effective in inducing the production of interferon gamma (IFN-γ, immune system proteins) mediated by CD4+ and CD8+ T lymphocyte defense cells.
The protection tests were carried out at the Biosafety Level 3 (NB-3) Laboratory of the Virology Research Center of FMRP. Transgenic mice and hamsters were used, models prepared to simulate severe and moderate Covid-19, respectively. After the application of the vaccine and infection by the virus (Wuhan, delta and omicron variants), the animals were protected. Protection was demonstrated through maintenance of body weight, 100% survival, reduction in pulmonary and cerebral viral load and absence of pulmonary pathology.
“An infected animal without immunization loses weight and dies within ten to 15 days due to the infection,” explains Julia. “So the first obvious endpoint was weight loss and mortality.”
Post-doctorate
If approved by Anvisa, Julia will participate in the next phase of clinical trials and return to work on her original project.
The immunologist’s work won the 2024 USP Outstanding Theses Award in the Innovation category. The thesis Development of chimeric protein and evaluation of its potential as a vaccine against COVID-19 can be read here.
More information: juliatcastro@hotmail.com, with Julia Teixeira de Castro
English version: Nexus Traduções, edited by Denis Pacheco
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A reprodução de matérias e fotografias é livre mediante a citação do Jornal da USP e do autor. No caso dos arquivos de áudio, deverão constar dos créditos a Rádio USP e, em sendo explicitados, os autores. Para uso de arquivos de vídeo, esses créditos deverão mencionar a TV USP e, caso estejam explicitados, os autores. Fotos devem ser creditadas como USP Imagens e o nome do fotógrafo.
A reprodução de matérias e fotografias é livre mediante a citação do Jornal da USP e do autor. No caso dos arquivos de áudio, deverão constar dos créditos a Rádio USP e, em sendo explicitados, os autores. Para uso de arquivos de vídeo, esses créditos deverão mencionar a TV USP e, caso estejam explicitados, os autores. Fotos devem ser creditadas como USP Imagens e o nome do fotógrafo.