Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project

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, 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

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.