AUTHOR=Valim Valéria , Martins-Filho Olindo Assis , Gouvea Maria da Penha Gomes , Camacho Luiz Antônio Bastos , Villela Daniel Antunes Maciel , de Lima Sheila Maria Barbosa , Azevedo Adriana Souza , Neto Lauro Ferreira Pinto , Domingues Carla Magda Allan Santos , de Medeiros Junior Nésio Fernandes , Moulaz Isac Ribeiro , Dias Laiza Hombre , Miyamoto Samira Tatiyama , Teixeira-Carvalho Andréa , Mill José Geraldo , Half Dose ChAdOx Study Group , Gouveia Thayná Martins , Thompson Beatriz Paoli , Lança Karen Evelin Monlevade , Lacerda Gabriela Curto Cristianes , Lenzi João Pedro Gonçalves , Ramos Sabrina de Souza , Pimentel Felipe de Castro , Forechi Ludimila , Ruchdeschel Thaís , Miossi João Pedro Moraes , Rassele Matheus Leite , Vieira Gabriel Smith Sobral , Pasti Laís , Henriques Allan Gonçalves , Amaral Maria Eduarda Morais Hibner , Ramos Alessandro Demoner , Surlo Heitor Filipe , Aguiar Laura Gonçalves Rodrigues , Grillo Luiza Lorenzoni , Pereira Matheus , Rizzi Ramon Borge , Muniz Sara Monteiro , Santos Hully Cantão dos , Roza Thais Luma de Oliveira , Silva Adriana Santos , Ferreira Lunara Baptista , Lallemand Karina , Machado Ketty Lysie Libardi Lira , Motta Tania Queiroz Reuter , Jubini Jaquelini , Mattos Carla Cristina Moraes de , Vieira Maria Angélica Calegário , Lyra Danielle Grillo Pacheco , Silva Cristiano Soares da , Rodrigues Rodrigo Ribeiro , Reblin Luís Carlos , Cardoso Orlei , Barrera Lely Stella Guzmán , Pércio Jhader , Rocha Ismael Artur da Costa , Prado Roberta Oliveira , Pereira Agnes Antônia Sampaio , Miranda Vitor Hugo Simões , Alessio Gláucia Diniz , Araújo Fernanda Fortes de , Speziali Elaine , Pereira Christiane Costa , Alves Clarice Carvalho , Carvalho Kétyllen Reis Andrade de , Figueiredo Anna Carolina Cançado , Santos Liliane Martins dos , Garcia Cristiana Couto , Carvalho Nani Oliveira , Reis Laise Rodrigues , Santos Tâmilla Mayane Alves Fidelis dos , Brito-de-Souza Joaquim Pedro , Costa Camila Medeiros , Vale Isabela Natália Pascoal Campos do , Henriques Priscilla Miranda , Maciel Poliane Silva , Torres Thais Abdala , Oliveira Nathália Werneck Cézar de , Oliveira Gabriela de , Fernandes Luana Oliveira Borges , Gonçalves Andreza Parreiras , Andrade Jesuanne Carla Silva , Silva Ladson Lúcio Viana da , Barbosa Armanda Moreira Mattoso , Araújo Maria Beatriz Martins , Rocha Bruna Luiza Fonte Boa , Antonelli Lis Ribeiro do Valle , Campi-Azevedo Ana Carolina , Peruhype-Magalhães Vanessa , Schwarcz Waleska Dias , Alves Nathalia dos Santos , Horbach Ingrid Siciliano , Souza Ariane Faria de , Dias Brenda de Moura , Setatino Bruno Pimenta , Denani Caio Bidueira TITLE=Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.966416 DOI=10.3389/fimmu.2022.966416 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.