ABSTRACT
ObjectivesTo evaluate heterologous scheme in children 3-18 y/o using two SARS-CoV-2 r-RBD protein vaccines. MethodsA phase I/II open-label, adaptive and multicenter trial evaluated the safety and immunogenicity of two doses of SOBERANA02 and a heterologous third dose of SOBERANA Plus in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (in phase I) and safety/immunogenicity (in phase II) measured by anti-RBD IgG ELISA, molecular and live-virus neutralization tests and specific T-cells response. An immunobridging and prediction of efficacy were additional analysis. ResultsLocal pain was the unique adverse event with >10% frequency, none was serious or severe. Two doses of SOBERANA 02 elicited humoral immune response similar to natural infection; the third dose increased significantly the response in all children, similar to that achieved in vaccinated young adults and higher than in convalescents children. The neutralizing titer was evaluated in a participants subset: all had neutralizing antibodies vs. alpha and delta; 97.9% vs. beta. GMT was 173.8 (CI 95% 131.7; 229.5) vs. alpha, 142 (CI 95% 101.3; 198.9) vs. delta and 24.8 (CI 95% 16.8; 36.6) vs. beta. An efficacy over 90% was estimated. ConclusionHeterologous scheme was safe and immunogenic in children 3-18 y/o. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000374
Subject(s)
PainABSTRACT
Background SOBERANA 02 is a COVID19 conjugate vaccine candidate based on SARS CoV2 recombinant RBD conjugated to tetanus toxoid. SOBERANA Plus antigen is dimericRBD. Here we report safety, reactogenicity and immunogenicity from phase I and IIa clinical trials using two doses SOBERANA 02 (homologous protocol) and three doses (homologous) or heterologous (with SOBERANA Plus) protocols. Method We performed an open label, monocentric, sequential and adaptive phase I for evaluating safety, reactogenicity and exploring immunogenicity of SOBERANA 02 in two formulations (15 and 25 microg) in 40 subjects, 19 to 59 years old. Phase IIa was open label including 100 volunteers 19 to 80 years, receiving two doses of SOBERANA 02 25 microg. In both trials, half of volunteers received a third dose of SOBERANA 02, half received a heterologous dose of SOBERANA Plus 50 microg. Primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity evaluated by anti RBD IgG ELISA, molecular neutralization test of RBD:hACE2 interaction, live virus neutralization test and specific T cells response. Results The most frequent AE was local pain, other AEs had frequencies lower than 5%. No serious related AEs were reported. Phase IIa confirmed the safety results in 60 to 80 years subjects. In phase I SOBERANA 02 25 microg elicited higher immune response than SOBERANA 02 15 microg; in consequence, the higher dose progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02 25 microg. even in 60 to 80 age range. Two doses of SOBERANA02 25 microg elicited an immune response similar to that of the Cuban Convalescent Serum Panel; it was higher after both the homologous and heterologous third doses; the heterologous scheme showing a higher immunological response. Conclusions SOBERANA 02 was safe and immunogenic in persons aged 19 to 80 years, eliciting neutralizing antibodies and specific T cell response. Highest immune responses were obtained in the heterologous three doses protocol. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000340 and https://rpcec.sld.cu/trials/RPCEC00000347