Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials.

BACKGROUND: SOBERANA 02 is a COVID-19 vaccine based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid (TT). SOBERANA Plus antigen is dimeric-RBD. Here we report safety and immunogenicity from phase I and IIa clinical trials using two-doses of SOBERANA 02 and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols. METHOD: We performed an open-label, sequential and adaptive phase I to evaluate safety and explore the immunogenicity of SOBERANA 02 in two formulations (15 or 25 µg RBD-conjugated to 20 µg of TT) in 40 subjects, 19-59-years-old. Phase IIa was open-label including 100 volunteers 19-80-years, receiving two doses of SOBERANA 02-25 µg. In both trials, half of volunteers were selected to receive a third dose of the corresponding SOBERANA 02 and half received a heterologous dose of SOBERANA Plus. Primary outcome was safety. The secondary outcome was immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization of RBD:hACE2 interaction, live-virus-neutralization and specific T-cells response. RESULTS: The most frequent adverse event (AE) was local pain, other AEs had frequencies ≤ 5%. No serious related-AEs were reported. Phase IIa confirmed the safety in 60 to 80-years-old subjects. In phase-I SOBERANA 02-25 µg elicited higher immune response than SOBERANA 02-15 µg and progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02-25 µg even in 60-80-years. Two doses of SOBERANA02-25 µg elicited an immune response similar to that of the Cuban Convalescent Serum Panel and it was higher after the homologous and heterologous third doses. The heterologous scheme showed a higher immunological response. Anti-RBD IgG neutralized the delta variant in molecular assay, with a 2.5-fold reduction compared to D614G neutralization. CONCLUSIONS: SOBERANA 02 was safe and immunogenic in persons aged 19-80 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, https://rpcec.sld.cu/trials/RPCEC00000347.

Ensayo clínico de reto, para evaluar una cepa candidata a vacuna contra el cólera / Challenge clinical trial for evaluation of a vaccine candidate strain against cholera

INTRODUCCIÓN: la cepa atenuada 638 Vibrio cholerae O1 El Tor, Ogawa, ha demostrado ser bien tolerada e inmunogénica por vía oral en estudios realizados en voluntarios sanos. OBJETIVO: se evaluó la protección conferida contra el cólera, en un ensayo clínico de reto, para el escalado tecnológico y farmacéutico de este candidato vacunal como ingrediente activo a escala industrial. MÉTODOS: en el estudio participaron 21 voluntarios sanos, 12 de ellos recibieron el candidato vacunal, y 9 ingirieron un placebo; 28 d después, todos recibieron una dosis infectante de una cepa virulenta de V.cholerae. RESULTADOS: la diarrea se registró en 7 de los 9 placebos, mientras que ninguno de los voluntarios vacunados presentó diarrea. Los voluntarios placebos del grupo sanguíneo O, tuvieron diarreas con mayor frecuencia e intensidad. Todos los voluntarios en el grupo placebo excretaron V. cholerae mientras que solo 3 (25 por ciento) de los 12 vacunados la excretaron. CONCLUSIONES: en este modelo de ensayo de reto, la cepa 638 demostró proteger contra la diarrea producida por una cepa virulenta de V. cholerae.

INTRODUCTION: live attenuated oral Vibrio cholerae O1 El Tor, Ogawa strain 638 has demonstrated to be well tolerated and immunogenic when administrated orally in studies carried out in healthy volunteers. OBJECTIVE: to evaluate the protection against cholera infection in a challenge clinical trial, for the technological and pharmaceutical scale-up of this vaccinal candidate as active ingredient at industrial level. METHOD: a total of 21 healthy volunteers were involved in this trial; the vaccine candidate was administered to 12 of them and the remaining nine were given the placebo. Twenty eight days later, all of them received an infective dose of a V. cholerae virulent strain. RESULTS: diarrheas were observed in 7 out of 9 placebos whereas not a single vaccinated volunteer showed diarrheas. More frequent and intense loose stools were found in the placebo volunteers with O-blood group. All volunteers in he placebo group excreted V. cholerae, but only three (25 percent) out of the 12 vaccinated volunteers did so. CONCLUSION: in this challenge clinical trial model, the 638 strain proved to protect people against the diarrhea caused by a virulent V. cholerae strain.

[Challenge clinical trial for evaluation of a vaccine candidate strain against cholera]. / Ensayo clínico de reto, para evaluar una cepa candidata a vacuna contra el cólera.

INTRODUCTION: live attenuated oral Vibrio cholerae Ol El Tor, Ogawa strain 638 has demonstrated to be well tolerated and immunogenic when administrated orally in studies carried out in healthy volunteers. OBJECTIVES: to evaluate the protection against cholera infection in a challenge clinical trial, for the technological and pharmaceutical scale-up of this vaccinal candidate as active ingredient at industrial level. METHODS: a total of 21 healthy volunteers were involved in this trial; the vaccine candidate was administered to 12 of them and the remaining nine were given the placebo. Twenty eight days later, all of them received an infective dose of a V. cholerae virulent strain. RESULTS: diarrheas were observed in 7 out of 9 placebos whereas not a single vaccinated volunteer showed diarrheas. More frequent and intense loose stools were found in the placebo volunteers with O-blood group. All volunteers in he placebo group excreted V. cholerae, but only three (25%) out of the 12 vaccinated volunteers did so. CONCLUSION: in this challenge clinical trial model, the 638 strain proved to protect people against the diarrhea caused by a virulent V. cholerae strain.