The pandemic of coronavirus infection 2019 (COVID-19), caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. New research efforts are, therefore, being made to develop vaccines and antiviral drugs that will help prevent or treat the condition and reduce the mortality rate.
A new study, released on the medRxiv* preprint server, detailing results from a single dose of the FINLAY FR 1A dimeric binding receptor base (RBD) vaccine during a phase I clinical trial with 30 COVID-19 convalescents to test its potential for increased natural immunity.
Need for new vaccines
While several vaccines have received emergency use approval (EUA), with many more in the early clinical trial phase, their effectiveness and ability to provide protection to the latest variants of the virus. This new predictor reports on the safety and efficacy performance of a new vaccine candidate (FINLAY-FR-1A) during phase I testing.
The virus binds to the host cell through its RBD within the S1 subunit of the immunodominant spike antigen. The spike is naturally in the shape of a trimeric.
The three RBDs can be in ‘up’ or ‘down’ concordance, based on whether they can bind to the host cell receptor, the angiotensin converting enzyme 2 (ACE2). The RBD-ACE2 binding leads to spike and intra-viral protein movement, leading to fetal disease.
The FINLAY-FR-1A vaccine is based on a recombinant dimeric form of the receptor binding domain (d-RBD), which is in clinical trials in Cuba. Phase I tests have revealed a desirable safety profile.
Topics of study
The current study examines the safety and humoral response following a single dose of this vaccine candidate, known as FINLAY-FR-1A. The study includes 30 people at the stage of recovery after SARS-CoV-2 infection. Everyone had a polymerase chain test (PCR) test for the virus that became negative two months or more from the start of the study.
There were three groups. The first group had moderate COVID-19, the second group had asymptomatic disease, and the third group was seropositive but never had advanced PCR.
Safety profile
Vaccine-related adverse events were assessed for frequency and severity. Previous studies have shown that three-quarters of those who were seropositive and received a single dose of mRNA vaccine developed adverse events, which is much more frequent than that seen in seronegative vaccine recipients.
With the current vaccine, adverse events have been detected in six people, accounting for one-fifth of the group. Seven of the adverse events were total and were mainly local incidents. This supports safety conclusions from an earlier study on non-infected subjects.
Anti-RBD antibodies
Of the 30 participants, anti-RBD immunoglobulin G (IgG) antibodies were significantly increased on day 7 after vaccination, as reported earlier in health care workers. The peak was reached on day 28, at 722 AU / mL, which is 21-fold the pre-vaccination rate, and ten times higher than the pre-vaccination Cuban Average Serum Panel (CCSP).
This is in line with the results obtained with a single dose of the Pfizer / BioNTech mRNA BNT162b2 vaccine. Anti-RBD IgG was found to be increased in all three groups, with four non-respondents among them, responding to 13% of the total group.
Antibody action
Prior to vaccination, RBD-ACE2 binding was blocked by less than 60%; after a single dose, the inhibition ratio in 26/30 subjects increased, over time, to 94% by day 14.
The majority achieved this level of antibody-mediated inhibition even earlier, by day 7. This compares with the 47% inhibition achieved by the CCSP.
The researchers also observed a 50% molecular virus neutralization titer (mVNT50) – that is, the serum titer weakens 50% of RBD-ACE2 interactions. The average geometric titer mVNT50 (GMT), of 222240, on day 28 after vaccination, was almost 120-fold higher than the pre-vaccination titer of 2222, and 27-fold higher than the CCSP value of ~ 83.
The GMT for the standard virus neutralization titer assay (cVNT50), against the live virus, was fourfold higher than the GMT mean for CCSP.
What is the impact?
These results indicate that a single dose of this vaccine candidate is both safe and immunogenic in COVID-19 convalescent patients. The safety profile is excellent, while the antibody response is 20-fold stimulated at one week after vaccination.
Viral neutralization is also fourfold higher than that of the pre-vaccination serum convalescent neutralizing antibody titer.
The FINLAY-FR-1A can therefore move into phase II clinical trials to test its efficacy and to work out a common protocol for strengthening immunity in this group of COVID-19 convalescent patients. .
* Important message
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or treated as fixed information.