PMID- 35998623
OWN - NLM
STAT- MEDLINE
DCOM- 20221115
LR  - 20221227
IS  - 2666-6340 (Electronic)
IS  - 2666-6359 (Print)
IS  - 2666-6340 (Linking)
VI  - 3
IP  - 11
DP  - 2022 Nov 11
TI  - Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 
      and SOBERANA Plus vaccines: Phase IIb clinical trial in adults.
PG  - 760-773.e5
LID - S2666-6340(22)00320-8 [pii]
LID - 10.1016/j.medj.2022.08.001 [doi]
AB  - BACKGROUND: SOBERANA 02 has been evaluated in phase I and IIa studies comparing 
      homologous versus heterologous schedule (this one, including SOBERANA Plus). 
      Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 
      02 in a two- or three-dose heterologous scheme in adults. METHOD: Phase IIb was a 
      parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled 
      trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses 
      of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of 
      dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active 
      ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of 
      seroconverted subjects with >/=4-fold the anti-RBD immunoglobulin G (IgG) 
      concentration. Secondary outcomes were safety, reactogenicity, and neutralizing 
      antibodies. FINDINGS: Seroconversion rate in vaccinees was 76.3% after two doses 
      and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). 
      Neutralizing IgG antibodies were detected against D614G and variants of concern 
      (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were 
      detected 7-8 months after the third dose. The frequency of serious adverse events 
      (AEs) associated with vaccination was very low (0.1%). Local pain was the most 
      frequent AE. CONCLUSIONS: Two doses of SOBERANA 02 were safe and immunogenic in 
      adults. The heterologous combination with SOBERANA Plus increased neutralizing 
      antibodies, detectable 7-8 months after the third dose. TRIAL REGISTRY: 
      https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by 
      Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y 
      Tecnica (FONCI-CITMA-Cuba, contract 2020-20).
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Toledo-Romani, Maria Eugenia
AU  - Toledo-Romani ME
AD  - "Pedro Kouri" Tropical Medicine Institute, Av "Novia del Mediodia", Kv 6 1/2, La 
      Lisa, Havana 11400, Cuba.
FAU - Garcia-Carmenate, Mayra
AU  - Garcia-Carmenate M
AD  - "19 de Abril" Polyclinic, Tulipan St. between Panorama y Oeste, Nuevo Vedado, 
      Plaza de la Revolucion, Havana 10400, Cuba.
FAU - Verdecia-Sanchez, Leslyhana
AU  - Verdecia-Sanchez L
AD  - Clinic #1, 21 St. and 190, La Lisa, Havana, Cuba.
FAU - Perez-Rodriguez, Suzel
AU  - Perez-Rodriguez S
AD  - "19 de Abril" Polyclinic, Tulipan St. between Panorama y Oeste, Nuevo Vedado, 
      Plaza de la Revolucion, Havana 10400, Cuba.
FAU - Rodriguez-Gonzalez, Meybis
AU  - Rodriguez-Gonzalez M
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Valenzuela-Silva, Carmen
AU  - Valenzuela-Silva C
AD  - Cybernetics, Mathematics and Physics Institute, 15th St. #55, Vedado, Plaza de la 
      Revolucion, Havana 10400, Cuba.
FAU - Paredes-Moreno, Beatriz
AU  - Paredes-Moreno B
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Sanchez-Ramirez, Belinda
AU  - Sanchez-Ramirez B
AD  - Center of Molecular Immunology, 15th Avenue and 216 St, Siboney, Playa, Havana, 
      Cuba.
FAU - Gonzalez-Mugica, Raul
AU  - Gonzalez-Mugica R
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Hernandez-Garcia, Tays
AU  - Hernandez-Garcia T
AD  - Center of Molecular Immunology, 15th Avenue and 216 St, Siboney, Playa, Havana, 
      Cuba.
FAU - Orosa-Vazquez, Ivette
AU  - Orosa-Vazquez I
AD  - Center of Molecular Immunology, 15th Avenue and 216 St, Siboney, Playa, Havana, 
      Cuba.
FAU - Diaz-Hernandez, Marianniz
AU  - Diaz-Hernandez M
AD  - Center of Molecular Immunology, 15th Avenue and 216 St, Siboney, Playa, Havana, 
      Cuba.
FAU - Perez-Guevara, Maria Teresa
AU  - Perez-Guevara MT
AD  - National Civil Defense Research Laboratory, San Jose de las Lajas, Mayabeque, 
      Cuba.
FAU - Enriquez-Puertas, Juliet
AU  - Enriquez-Puertas J
AD  - National Civil Defense Research Laboratory, San Jose de las Lajas, Mayabeque, 
      Cuba.
FAU - Noa-Romero, Enrique
AU  - Noa-Romero E
AD  - National Civil Defense Research Laboratory, San Jose de las Lajas, Mayabeque, 
      Cuba.
FAU - Palenzuela-Diaz, Ariel
AU  - Palenzuela-Diaz A
AD  - Centre for Immunoassays, 134 St. and 25, Cubanacan, Playa, Havana 11600 Cuba.
FAU - Baro-Roman, Gerardo
AU  - Baro-Roman G
AD  - Centre for Immunoassays, 134 St. and 25, Cubanacan, Playa, Havana 11600 Cuba.
FAU - Mendoza-Hernandez, Ivis
AU  - Mendoza-Hernandez I
AD  - National Clinical Trials Coordinating Center, 5th Avenue and 62, Miramar, Playa, 
      Havana, Cuba.
FAU - Munoz, Yaima
AU  - Munoz Y
AD  - National Clinical Trials Coordinating Center, 5th Avenue and 62, Miramar, Playa, 
      Havana, Cuba.
FAU - Gomez-Maceo, Yanet
AU  - Gomez-Maceo Y
AD  - Clinic #1, 21 St. and 190, La Lisa, Havana, Cuba.
FAU - Santos-Vega, Bertha Leysi
AU  - Santos-Vega BL
AD  - "19 de Abril" Polyclinic, Tulipan St. between Panorama y Oeste, Nuevo Vedado, 
      Plaza de la Revolucion, Havana 10400, Cuba.
FAU - Fernandez-Castillo, Sonsire
AU  - Fernandez-Castillo S
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba. Electronic address: sfernandez@finlay.edu.cu.
FAU - Climent-Ruiz, Yanet
AU  - Climent-Ruiz Y
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Rodriguez-Noda, Laura
AU  - Rodriguez-Noda L
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Santana-Mederos, Darielys
AU  - Santana-Mederos D
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Garcia-Vega, Yanelda
AU  - Garcia-Vega Y
AD  - Center of Molecular Immunology, 15th Avenue and 216 St, Siboney, Playa, Havana, 
      Cuba.
FAU - Chen, Guang-Wu
AU  - Chen GW
AD  - Chengdu Olisynn Biotech. Co. Ltd., Chengdu 610041, People's Republic of China; 
      State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu 610041, People's Republic of China.
FAU - Doroud, Delaram
AU  - Doroud D
AD  - Pasteur Institute of Iran, No. 69, Pasteur Avenue, Tehran 1316943551, Islamic 
      Republic of Iran.
FAU - Biglari, Alireza
AU  - Biglari A
AD  - Pasteur Institute of Iran, No. 69, Pasteur Avenue, Tehran 1316943551, Islamic 
      Republic of Iran.
FAU - Boggiano-Ayo, Tammy
AU  - Boggiano-Ayo T
AD  - Center of Molecular Immunology, 15th Avenue and 216 St, Siboney, Playa, Havana, 
      Cuba.
FAU - Valdes-Balbin, Yury
AU  - Valdes-Balbin Y
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Rivera, Daniel G
AU  - Rivera DG
AD  - Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, 
      University of Havana, Havana 10400, Cuba.
FAU - Garcia-Rivera, Dagmar
AU  - Garcia-Rivera D
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba.
FAU - Verez-Bencomo, Vicente
AU  - Verez-Bencomo V
AD  - Finlay Vaccine Institute, 21st Avenue N masculine 19810 Between 198 and 200 St, Atabey, 
      Playa, Havana, Cuba. Electronic address: vicente_verez@finlay.edu.cu.
CN  - SOBERANA Research Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220808
PL  - United States
TA  - Med
JT  - Med (New York, N.Y.)
JID - 101769215
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Vaccines)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Adult
MH  - Humans
MH  - SARS-CoV-2
MH  - *COVID-19/prevention & control
MH  - Antibodies, Neutralizing
MH  - *Vaccines
MH  - Immunoglobulin G
PMC - PMC9359498
OTO - NOTNLM
OT  - COVID-19
OT  - Translation to patients
OT  - conjugate vaccine
OT  - heterologous schedule
OT  - phase IIb clinical trial
OT  - recombinant RBD
COIS- Declaration of interests M.E.T.-R., M.G.-C., L.V.-S., S.P.-R., C.V.-S., 
      M.T.P.-G., J.E.-P., E.N.-R., A.P.-D., G.B.-R., I.M.-H., Y.M., Y.G.-M., B.L.S.-V., 
      G.-W.-C., D.D., A.B., and D.G.R. declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper. M.R.-G., B.P.-M., B.S.-R., R.G.-M., 
      T.H.-G., I.O.-V., M.D.-H., S.F.-C., Y.C.-R., L.R.-N., D.S.-M., Y.G.-V., T.B.-A., 
      Y.V.-B., D.G.-R., and V.V.-B. work at Finlay Vaccine Institute or the Center of 
      Molecular Immunology, institutions that develop and manufacture the vaccine 
      candidates, but they have not received an honorarium for this paper. B.S.-R., 
      S.F.-C., Y.C.-R., L.R.-N., D.S.-M., Y.V.-B., D.G.R., D.G.-R., and V.V.-B. have 
      filed patent applications related to the vaccine SOBERANA 02.
FIR - Cubas-Curbelo, Mailin
IR  - Cubas-Curbelo M
FIR - Rodriguez-Castillo, Pedro Gabriel
IR  - Rodriguez-Castillo PG
FIR - Acevedo-Martinez, Yosmel
IR  - Acevedo-Martinez Y
FIR - Estoque-Cabrera, Solangel
IR  - Estoque-Cabrera S
FIR - Avila-Cabreja, Jose Alejandro
IR  - Avila-Cabreja JA
FIR - Alfaro-Guzman, Ainadis
IR  - Alfaro-Guzman A
FIR - Zulueta-Perez, Lilian
IR  - Zulueta-Perez L
FIR - Espino-Rojas, Niurka Tamara
IR  - Espino-Rojas NT
FIR - Medinas-Santos, Gloria Margarita
IR  - Medinas-Santos GM
FIR - Sarda-Rodriguez, Ileana Luisa
IR  - Sarda-Rodriguez IL
FIR - Acosta-Martinez, Mario Alejandro
IR  - Acosta-Martinez MA
FIR - Reyes-Matienzo, Radamet
IR  - Reyes-Matienzo R
FIR - Coviella-Artime, Jose Manuel
IR  - Coviella-Artime JM
FIR - Morffi-Cinta, Irania
IR  - Morffi-Cinta I
FIR - Martinez-Perez, Marisel
IR  - Martinez-Perez M
FIR - Valera-Fernandez, Rodrigo
IR  - Valera-Fernandez R
FIR - Garces-Hechavarria, Aniurka
IR  - Garces-Hechavarria A
FIR - Martinez-Bedoya, Dayle
IR  - Martinez-Bedoya D
FIR - Garrido-Arteaga, Raine
IR  - Garrido-Arteaga R
FIR - Cardoso-SanJorge, Felix
IR  - Cardoso-SanJorge F
FIR - Ramirez-Gonzalez, Ubel
IR  - Ramirez-Gonzalez U
FIR - Quintero-Moreno, Lauren
IR  - Quintero-Moreno L
FIR - Ontivero-Pino, Ivis
IR  - Ontivero-Pino I
FIR - Martinez-Rivera, Roselyn
IR  - Martinez-Rivera R
FIR - Guillen-Obregon, Berta
IR  - Guillen-Obregon B
FIR - Lora-Garcia, Janet
IR  - Lora-Garcia J
FIR - Medina-Napoles, Maite
IR  - Medina-Napoles M
FIR - Espi-Avila, Jennifer
IR  - Espi-Avila J
FIR - Fontanies-Fernandez, Marcos
IR  - Fontanies-Fernandez M
FIR - Dominguez-Penton, Yeney Regla
IR  - Dominguez-Penton YR
FIR - Bergado-Baez, Gretchen
IR  - Bergado-Baez G
FIR - Pi-Estopinan, Franciscary
IR  - Pi-Estopinan F
FIR - Ojito-Magaz, Eduardo
IR  - Ojito-Magaz E
FIR - Rodriguez, Misladys
IR  - Rodriguez M
FIR - Cruz-Sui, Otto
IR  - Cruz-Sui O
FIR - Garcia-Montero, Majela
IR  - Garcia-Montero M
FIR - Dubed-Echevarria, Marta
IR  - Dubed-Echevarria M
FIR - Garcia-Lopez, Elena
IR  - Garcia-Lopez E
FIR - Galano-Frutos, Evelyn
IR  - Galano-Frutos E
FIR - Perez-Perez, Alina
IR  - Perez-Perez A
FIR - Morales-Ruano, Susana
IR  - Morales-Ruano S
FIR - Brito-Pascual, Idalmis
IR  - Brito-Pascual I
FIR - Amoroto, Maite
IR  - Amoroto M
FIR - Arteaga-Garcia, Amaylid
IR  - Arteaga-Garcia A
EDAT- 2022/08/24 06:00
MHDA- 2022/11/16 06:00
PMCR- 2022/08/08
CRDT- 2022/08/23 18:43
PHST- 2022/01/31 00:00 [received]
PHST- 2022/05/17 00:00 [revised]
PHST- 2022/08/02 00:00 [accepted]
PHST- 2022/08/24 06:00 [pubmed]
PHST- 2022/11/16 06:00 [medline]
PHST- 2022/08/23 18:43 [entrez]
PHST- 2022/08/08 00:00 [pmc-release]
AID - S2666-6340(22)00320-8 [pii]
AID - 10.1016/j.medj.2022.08.001 [doi]
PST - ppublish
SO  - Med. 2022 Nov 11;3(11):760-773.e5. doi: 10.1016/j.medj.2022.08.001. Epub 2022 Aug 
      8.