Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial

Abstract

This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46–23.13), 11.12 (2.74–45.09), and 20.70 (5.05–84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27–25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Immunogenicity and safety of RAZI recombinant spike protein vaccine (RCP) as a booster dose after priming with BBIBP-CorV: a parallel two groups, randomized, double blind trial

“…A detailed description of RCP preparation has been published before [ 19 ]. RCP has shown promising safety and induced robust and long-lasting humoral and cellular immune responses in preclinical and all three phases of clinical trials [ 20 – 22 ] (phase III trial results are under publication). Sinopharm inactivated virus vaccine (BBIBP-CorV), which the World Health Organization approves, has been widely used in many countries, including Iran’s vaccination program (about 70% of the coverage) [ 23 ].…”

A Meta-Analysis on the Association between Peptic Ulcer Disease and COVID-19 Severity

“…To date, more than 200 COVID-19 vaccine candidates are in various stages of development, and more than 50 of these candidates have started clinical trials. These candidates may use inactivated or live attenuated viruses, nucleic acids (DNA or RNA), viral vectors, recombinant proteins or virus particles [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. WHO is committed to keeping the momentum for boosting access to COVID-19 vaccinations going and will continue to assist countries in expediting vaccine delivery in order to save lives and prevent people from becoming seriously ill.…”