Gilda Lemos-Pérez

A phase 1–2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382), with parallel groups, involving 1161 participants, was designed to assess the safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in 55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe—no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headaches predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p < 0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in 55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p <0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

COVID-19 is a respiratory viral disease caused by a new coronavirus called SARS-CoV-2. This disease has spread rapidly worldwide with a high rate of morbidity and mortality. The receptor-binding domain (RBD) of protein spike (S) mediates the attachment of the virus to the host’s cellular receptor. The RBD domain constitutes a very attractive target for subunit vaccine development due to its ability to induce a neutralizing antibody response against the virus. With the aim of boosting the immunogenicity of RBD, it was fused to the extracellular domain of CD154, an immune system modulator molecule. To obtain the chimeric protein, stable transduction of HEK-293 was carried out with recombinant lentivirus and polyclonal populations and cell clones were obtained. RBD-CD was purified from culture supernatant and further characterized by several techniques. RBD-CD immunogenicity evaluated in mice and non-human primates (NHP) indicated that recombinant protein was able to induce a specific and high IgG response after two doses. NHP sera also neutralize SARS-CoV-2 infection of Vero E6 cells. RBD-CD could improve the current vaccines against COVID-19, based in the enhancement of the host humoral and cellular response. Further experiments are necessary to confirm the utility of RBD-CD as a prophylactic vaccine and/or booster purpose.

Background: Multiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity of a SARS-CoV-2 recombinant spike RBD protein novel vaccine. Methods: A phase 1-2, randomized, double-blind, placebo-controlled trial was done. Subjects were randomly distributed in 3 groups: placebo, 25 and 50µg RBD. The product was applied intramuscularly, 0·5 mL in the deltoid region. During the first phase, two immunization schedules were studied: 0-14-28 and 0-28-56 days. In phase 2, only the short scheme was evaluated. The main endpoints were: safety and proportion of subjects with seroconversion of anti-RBD IgG antibodies to SARS-CoV-2. The percentage of inhibition of RBD-ACE-2 binding and levels of neutralizing antibodies were also evaluated. This study was registered with Cuban Public Clinical Trial Registry (WHO accepted Primary Registry), RPCEC00000346. Findings: The product was well tolerated. Severe adverse events were not reported. Adverse reactions were minimal, mostly mild and local (from the injection site), resolved in the first 24-48 hours without medication. In phase 1, at day 56 (28 days after the short vaccination schedule) seroconversion of anti-RBD IgG was seen in 95·2% of the participants (20/21) for the 50μg group, 81% (17/21) in the 25μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 80% (8/10) and 94·7% (18/19) of the subjects for the 50 and 25μg groups, respectively. For the long schedule, at day 70 (14 days after the third dose) seroconversion of anti-RBD IgG was seen in 100% of the participants (21/21) of the 50μg group, 94·7% (18/19) in the 25μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 95% of the subjects (19/20) for the 50μg group and 93·8% of the participants (15/16) for the 25μg group. In phase 2, at day 56 seroconversion of anti-RBD IgG was seen in 89·2% of the participants (214/240) for the 50μg group, 77·7% (185/238) for the 25μg group, and 4·6% in the placebo group (11/239); whereas neutralizing antibodies to SARS-CoV-2 were seen in 97·3% of the participants (146/150) for the 50μg group and 95·1% of the participants (58/61) for the 25μg group. Interpretation: Abdala vaccine against SARS-CoV-2 was safe, well tolerated and induced humoral immune responses against SARS-CoV-2 among adults from 19 to 80 years of age. Trial Registration Details: his study was registered with Cuban Public Clinical Trial Registry (WHO accepted Primary Registry), RPCEC00000346. Funding Information: The study was financed by CIGB, Havana (products, reagents) and the Ministry of Public Health of Cuba (hospital facilities and general medical care of the participants). The funder of the study approved the study design, and participated in data interpretation and writing of the report. Declaration of Interests: Authors FHB, YMB, JQG, KUP, JLRR, MAV, MLF, GEGN, GLP, MAA, and VLMG, are employees of the Centre for Genetic Engineering and Biotechnology, Havana Network, where Abdala vaccine active ingredient is produced and the formulation was developed. The remaining authors have no conflict of interests. No honoraria, consulting fees or payments for seminar presentations, speeches or appearances have been received by any of the authors. Ethics Approval Statement: The protocol followed the Declaration of Helsinki guidelines and was evaluated by the Ethics and Review Committee of the Provincial Hospital "Saturnino Lora" in Santiago de Cuba (clinical site participating in the trial), who granted ethical approval of the study. Subjects gave written, informed consent to participate.

Aim To evaluate the safety and immunogenicity of a SARS-CoV-2 recombinant spike protein vaccine (Abdala), administered intramuscularly in different strengths and vaccination schedules. Method A phase 1-2, randomized, double-blind, placebo-controlled trial was done. Subjects were randomly distributed in 3 groups: placebo, 25 and 50µg RBD. The product was applied intramuscularly, 0.5 mL in the deltoid region. During the first phase, two immunization schedules were studied: short (0-14-28 days) and long (0-28-56 days). In phase 2, only the short scheme was evaluated. The main endpoints were: safety and proportion of subjects with seroconversion of anti-RBD IgG antibodies to SARS-CoV-2. Blood samples were collected in several points according to the corresponding vaccination schedule to determine the level of RBD-specific IgG antibodies (seroconversion rates and geometric mean of the titers), the percentage of inhibition of RBD-ACE-2 binding and levels of neutralizing antibodies. Results The product was well tolerated. Severe adverse events were not reported. Adverse reactions were minimal, mostly mild and local (from the injection site), resolved in the first 24-48 hours without medication. In phase 1, at day 56 (28 days after the third dose of the short vaccination schedule, 0-14-28 days) seroconversion of anti-RBD IgG was seen in 95.2 % of the participants (20/21) for the 50μg group and 81 % of the participants (17/21) for the 25μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 80 % of the participants (8/10) for the 50μg group and 94.7% of the participants (18/19) for the 25μg group. For the long schedule, at day 70 (14 days after the third dose) seroconversion of anti-RBD IgG was seen in 100% of the participants (21/21) for the 50μg group and 94.7% of the participants (18/19) for the 25μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 95 % of the participants (19/20) for the 50μg group and 93.8% of the participants (15/16) for the 25μg group In phase 2, at day 56 seroconversion of anti-RBD IgG was seen in 89.2% of the participants (214/240) for the 50μg group, 77.7% of the participants (185/238) for the 25μg group, and 4.6% in the placebo group (11/239); whereas neutralizing antibodies to SARS-CoV-2 were seen in 97.3% of the participants (146/150) for the 50μg group and 95.1% of the participants (58/61) for the 25μg group. Conclusion Abdala vaccine against SARS-CoV-2 was safe, well tolerated and induced humoral immune responses against SARS-CoV-2 among adults from 19 to 80 years of age. Trial registration / Review protocol RPCEC00000346. Cuban Public Clinical Trial Registry (WHO accepted Primary Registry). Available from: https://rpcec.sld.cu/en/trials/RPCEC00000346-En Information about the ethical aspects and IRB approval The protocol was approved by the Ethic Committee of the participating hospital and by the Cuban Regulatory Authority (Center for State Control of Drugs, Medical Devices and Equipment). Summary box COVID-19 is a serious global health problem. Vaccines are urgently needed to protect humanity. Multiple vaccine candidates are currently being evaluated. The article shows promising safety and immunogenicity results for a vaccine candidate, based on the recombinant RBD subunit of the spike protein.