Clinical studies of the Bahia vaccine against covid-19 will begin in September, in Salvador, with the participation of more than 30 local researchers. The tests will be carried out at Hospital da Bahia and, at first, will have the participation of 90 volunteers who have not yet been vaccinated. Yesterday, the National Health Surveillance Agency (Anvisa) authorized the RNA assay MCTI CIMATEC HDT, which uses the RNA replicon technology, which self-reproduces and generates antibodies. Currently, only vaccines under study follow this scheme.
The vaccine is being developed by the HDT Bio Corp laboratory (USA), in partnership with the National Service for Industrial Learning (Senai – Cimatec) of Bahia, and Gennova Biopharmaceuticals Ltd (India). The forecast is that in a year, it will be available.
Pre-clinical studies have been carried out in the USA since last year in mice and primates, in collaboration with Cimatec. The documents from the first stage concluded that, even with small doses, significant and lasting responses were obtained.
“In view of the technological platform of the vaccine, what we expect is that it will be a single dose, since small concentrations have been shown to be capable of promoting a high immune response”, says the technical leader of the project at Senai – Cimatec, and PhD in Biotechnology, Bruna Machado.
In the US, the phase I clinical trial was approved in July, and is expected to start this month, with 78 volunteers. In Brazil, phase I of the clinical study has now been approved, which foresees 90 healthy adults, male and female, between 18 and 55 years old. The forecast is that, in the coming days, the recruitment of volunteers will begin and Cimatec will receive the doses.
According to Roberto Badaró, infectious disease and professor at Senai – Cimatec, PhD in Immunology and Infectious Diseases, the main objective of this step is to assess safety and reactogenicity, that is, the ability of the vaccine to generate local adverse (or collateral) reactions or systemic. “Three different dose concentrations will be tested, verifying which one will show the most promise in the production of humoral and cellular immune response against the virus.”
The vaccine will be evaluated in a single dose schedule and also two doses at different intervals. The first group will receive two doses 29 days apart. The second will receive two with an interval of 57 days. The third will receive a single dose. Three dose levels (1 μg, 5 μg or 25 μg) will be evaluated in the approved clinical trial.
The studies also include phases 2 and 3, until the immunizing agent is approved for registration and production in Brazil. Once the safety in phase 1 is proven, phase 2 will begin, with the participation of 400 individuals. Step 3 will depend on the results of the previous one. For this, three to five thousand participants are expected. The tests will cost R$ 6 million.
Team that works in the research of the new vaccine
(Photo: Nara Gentil / MAIL)
How does the vaccine work?
The vaccine uses third-generation RNA technology: an RNA replicon molecule, which, in contact with the organism, has the ability to self-reproduce, generating messenger RNA, which teaches the body to produce antibodies. Among the advantages, it is a vaccine with great possibility of being applied in a single dose, capable of promoting a robust and lasting response, including against the different strains
The vaccine candidate consists of a lipid nanocarrier formulation called LION (Lipid InOrganic hybridized Nanoparticle) and a repRNA molecule that encodes the spike protein (S) of SARS-CoV-2.
“Until then, there is no approved vaccine in the world that uses replicon RNA. In Brazil, it is the first clinical study with an immunizing agent of this type. But the technology is being used to develop HIV vaccine and cancer treatment drugs. It is a promising technology that may allow future developments of vaccines for leishmaniasis, malaria and chikungunya, for example”, says Bruna Machado.
Understand how an immunizer is approved
Currently, there are four ways for a vaccine against covid-19 to be approved in the country: registration, emergency use, exceptional importation and importation by the Covax Facility consortium.
Regulatory approval of a vaccine against the Sars-CoV-2 virus requires the demonstration of safety and clinical benefit in a placebo-controlled efficacy study. The World Health Organization (WHO) and the Food and Drugs Administration (FDA, US regulatory agency equivalent to Anvisa) require vaccines to show at least 50% effectiveness.
In testing a vaccine, usually divided into phases 1, 2 and 3, scientists try to identify serious adverse effects and whether the inoculation is capable of inducing an immune response (ie, the body’s defense system).
Phase 1 trials typically involve dozens of volunteers; phase 2, hundreds; and those of phase 3, thousands. Before starting human trials, vaccines are tested on animals, usually on mice and then on monkeys.
Clinical studies of vaccines are conducted by pharmaceutical laboratories and research institutions. As a regulatory agency, Anvisa’s role is to define the sector’s regulation and evaluate the processes and data received from the point of view of their quality, efficacy and safety proof. From the submission of documents after completion of the clinical phase, the vaccine may receive registration to be then applied in the population.
Vaccines already approved by Anvisa: Pfizer, Astrazeneca, Coronavac, Janssen.
Vaccines with exceptional import authorization: Sputnik and Covaxin (suspended).
Vaccines with approved clinical studies: Butanvac, INO-4800, AZD2816, COVLP, Inactivated against Sars-CoV-2, SBC-2019, Sars-CoV-2 mRNA Vaccine and Cimatec HDT RNA Vaccine MCTI.
Vaccines with clinical studies under review: SpiNTec (UFMG), Versamune (USP), S-UFRJvac (UFRJ), Ad26.COV2.S and Vaccine of the State University of Ceará.
*With the guidance of Chief Reporter Perla Ribeiro