학술논문
Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project
Document Type
article
Author
Valéria Valim; Olindo Assis Martins-Filho; Maria da Penha Gomes Gouvea; Luiz Antônio Bastos Camacho; Daniel Antunes Maciel Villela; Sheila Maria Barbosa de Lima; Adriana Souza Azevedo; Lauro Ferreira Pinto Neto; Carla Magda Allan Santos Domingues; Nésio Fernandes de Medeiros Junior; Isac Ribeiro Moulaz; Laiza Hombre Dias; Samira Tatiyama Miyamoto; Andréa Teixeira-Carvalho; José Geraldo Mill; Half Dose ChAdOx Study Group; Thayná Martins Gouveia; Beatriz Paoli Thompson; Karen Evelin Monlevade Lança; Gabriela Curto Cristianes Lacerda; João Pedro Gonçalves Lenzi; Sabrina de Souza Ramos; Felipe de Castro Pimentel; Ludimila Forechi; Thaís Ruchdeschel; João Pedro Moraes Miossi; Matheus Leite Rassele; Gabriel Smith Sobral Vieira; Laís Pasti; Allan Gonçalves Henriques; Maria Eduarda Morais Hibner Amaral; Alessandro Demoner Ramos; Heitor Filipe Surlo; Laura Gonçalves Rodrigues Aguiar; Luiza Lorenzoni Grillo; Matheus Pereira; Ramon Borge Rizzi; Sara Monteiro Muniz; Hully Cantão dos Santos; Thais Luma de Oliveira Roza; Adriana Santos Silva; Lunara Baptista Ferreira; Karina Lallemand; Ketty Lysie Libardi Lira Machado; Tania Queiroz Reuter Motta; Jaquelini Jubini; Carla Cristina Moraes de Mattos; Maria Angélica Calegário Vieira; Danielle Grillo Pacheco Lyra; Cristiano Soares da Silva; Rodrigo Ribeiro Rodrigues; Luís Carlos Reblin; Orlei Cardoso; Lely Stella Guzmán Barrera; Jhader Pércio; Ismael Artur da Costa Rocha; Roberta Oliveira Prado; Agnes Antônia Sampaio Pereira; Vitor Hugo Simões Miranda; Gláucia Diniz Alessio; Fernanda Fortes de Araújo; Elaine Speziali; Christiane Costa Pereira; Clarice Carvalho Alves; Kétyllen Reis Andrade de Carvalho; Anna Carolina Cançado Figueiredo; Liliane Martins dos Santos; Cristiana Couto Garcia; Nani Oliveira Carvalho; Laise Rodrigues Reis; Tâmilla Mayane Alves Fidelis dos Santos; Joaquim Pedro Brito-de-Souza; Camila Medeiros Costa; Isabela Natália Pascoal Campos do Vale; Priscilla Miranda Henriques; Poliane Silva Maciel; Thais Abdala Torres; Nathália Werneck Cézar de Oliveira; Gabriela de Oliveira; Luana Oliveira Borges Fernandes; Andreza Parreiras Gonçalves; Jesuanne Carla Silva Andrade; Ladson Lúcio Viana da Silva; Armanda Moreira Mattoso Barbosa; Maria Beatriz Martins Araújo; Bruna Luiza Fonte Boa Rocha; Lis Ribeiro do Valle Antonelli; Ana Carolina Campi-Azevedo; Vanessa Peruhype-Magalhães; Waleska Dias Schwarcz; Nathalia dos Santos Alves; Ingrid Siciliano Horbach; Ariane Faria de Souza; Brenda de Moura Dias; Bruno Pimenta Setatino; Caio Bidueira Denani
Source
Frontiers in Immunology, Vol 13 (2022)
Subject
Language
English
ISSN
1664-3224
Abstract
Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18–49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423–663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048–1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.