Phase I clinical trial of two Cuban recombinant protein COVID-19 vaccines

The spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), consists of two subunits, including subunits S1 and S2. The S1 carries the receptor binding domain (RBD), which is responsible for the interaction of the virus with the angiotensin converting enzyme 2 (ACE2) receptor on the host cell, while the S2 subunit mediates the viral fusion.

Currently available SARS-CoV-2 vaccines stimulate the production of neutralizing antibodies against the RBD either by the adenovirus vector (AstraZeneca) or by the delivery of messenger ribonucleic acid (mRNA) material (Pfizer and Moderna); however, the novel nature of the latter has raised safety concerns. In a recently published paper by the preprint server medRxiv *, the authors discuss the results of clinical phase I studies for two new COVID-19 vaccine candidates based on recombinant RDB proteins and determine that they are safe and immunogenic.

Study: A randomized, double-blind, phase I clinical trial of two recombinant dimeric RBD-COVID-19 vaccine candidates: safety, reactogenicity, and immunogenicity. Image source: Surasak_Photo / Shutterstock.com

About the study

The two recombinant protein vaccines examined in the current study are named FINLAY-FR-1 and FINLAY-FR-1A, both of which are adsorbed on an alum adjuvant. In particular, the FINLAY FR-1 vaccine also carries Neisseria meningitides outer membrane vesicles, which have been used as adjuvant in several other vaccines.

Bacterial outer membrane vesicles can also facilitate antigen capture and presentation to T cells to stimulate an immune response. A total of 60 volunteers aged 19-59 with a healthy body mass index (BMI) were recruited for the study, who received either two doses of 25 micrograms (µg) of the FINLAY-FR-1 vaccine or 25 µg or 50. received µg FINLAY-FR-1A. Participants also received a third dose in either a heterologous or homologous regimen.

Background anti-SARS-CoV-2 antibodies were determined for each participant by enzyme-linked immunosorbent assay (ELISA) and virus neutralization assays immediately prior to vaccination. Blood samples were also drawn at the time of the second and third vaccinations and 28 days after the third dose. Active observations were made on each participant on days 1, 2, 3 and 7 after ingestion, and each participant was also asked to keep a diary to report adverse events.

Effectiveness and Safety of Recombinant Protein Vaccines

The first dose of any of the vaccines was observed to induce very little production of anti-SARS-CoV-2 RBD antibodies, with seroconversion after the third dose for FINLAY-FR-1 at 100%, 94.7% and 94.4% increase, FINLAY-FR-1A (25 µg) and FINLAY-FR-1A (50 µg).

Compared to controls, which consisted of convalescent sera from asymptomatic individuals, the vaccines induced a greater inhibition of the RBD-ACE2 interaction. In addition, the neutralizing antibody titers in all cases exceeded the titers in the sera in those who received homologous dosing of FINLAY-FR-1 and in 90% of participants on a heterologous regimen.

Live virus neutralizing antibodies were detected in 85% of subjects who received the FINLAY-FR-1 vaccine after the second dose and increased to 100% after the third dose. A lesser response from the FINLAY-FR-1A vaccine was seen at the lower dose, with 94.7% of participants exhibiting neutralizing antibodies to live viruses.

The neutralizing capacity of live viruses reported by these vaccines exceeds that reported by several inactivated virus vaccines and some adenovirus vector vaccines. Notably, this capacity is less than that reported by current mRNA COVID-19 vaccines.

The authors suggest that initial exposure to the vaccine is able to stimulate naive lymphocytes. Subsequent re-exposure quickly induces a secondary immune response that generates a large increase in neutralizing anti-RBD antibodies. It was observed that a third dose further improved the effect with few side effects. Taken together, these vaccines are also currently in the clinical trial phase as a booster dose for people who have already received another type of vaccine.

The FINLAY-FR-1 vaccine, which contained the outer membrane vesicles of Neisseria meningitides, was better able to stimulate an immune response in the participants, although more adverse events were reported.

Approximately 80% of all participants reported side effects of some kind during the study, most of which were mild and local and lasted less than 24 hours. During the course of the study, four events classified as serious occurred that represented pain and localized swelling.

Participants who received FINLAY-FR-1 reported more adverse events than those who received FINLAY-FR-1A at any dose, possibly due to the inclusion of bacterial outer membrane vesicles as an adjuvant. Importantly, a lower proportion of the adverse events reported for FINLAY-FR-1 were considered vaccine-derived, with most of the additional events reported as “general malaise”.

Overall, the difference in reported adverse events between groups was not statistically significant and was comparable to other currently available COVID-19 vaccines.

*Important NOTE

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, that guide clinical practice / health-related behavior or are treated as established information.


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