Efficacy and Safety of a COVID-19 Inactivated Vaccine in Healthcare Professionals in Brazil: The PROFISCOV Study

66 Pages Posted: 14 Apr 2021

See all articles by Ricardo Palacios

Ricardo Palacios

Instituto Butantan

Ana Paula Batista

Instituto Butantan

Camila Santos Nascimento Albuquerque

affiliation not provided to SSRN

Elizabeth González Patiño

affiliation not provided to SSRN

Joane do Prado Santos

Instituto Butantan

Mônica Tilli Reis Pessoa Conde

Instituto Butantan

Roberta de Oliveira Piorelli

Instituto Butantan

Luiz Carlos Pereira Júnior

Institute of Infectious Diseases Emilio Ribas

Sonia Mara Raboni

Federal University of Paraná - Virology Laboratory

Fabiano Ramos

Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) - School of Medicine

Gustavo Adolfo Sierra Romero

Universidade de Brasília (UnB)

Fábio Eudes Leal

Universidade Municipal de São Caetano do Sul (USCS)

Luis Fernando Aranha Camargo

Hospital Israelita Albert Einstein

Francisco Hideo Aoki

Universidade Estadual de Campinas (UNICAMP)

Eduardo Barbosa Coelho

University of São Paulo (USP) - Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Danise Senna Oliveira

Federal University of Pelotas (UFPel)

Cor Jesus Fernandes Fontes

Universidade Federal de Mato Grosso

Gecilmara Cristina Salviato Pileggi

affiliation not provided to SSRN

Ana Lúcia Lyrio de Oliveira

Universidade Federal de Mato Grosso do Sul

André Machado de Siqueira

Evandro Chagas National Institute of Infectious Diseases (INI), FIOCRUZ

Danielle Bruna Leal de Oliveira

University of São Paulo (USP)

Viviane Fongaro Botosso

Instituto Butantan

Gang Zeng

Sinovac Life Sciences

Qianqian Xin

Sinovac Life Sciences

Mauro Martins Teixeira

Federal University of Minas Gerais (UFMG)

Maurício Lacerda Nogueira

Faculdade de Medicina de São José de Rio Preto (FAMERP)

Esper Georges Kallas

University of São Paulo (USP)

Date Written: April 11, 2021

Abstract

Background: Vaccines are urgently needed to tackle the unprecedented morbidity and mortality of COVID-19. Administration of inactivated viruses are the common and mature platform of developing new vaccines. CoronaVac is an inactivated vaccine that has undergone preclinical tests and phase I/II clinical trials.

Methods: We conducted a randomised, double-blind, placebo-controlled phase 3 clinical trial with CoronaVac among healthy healthcare professionals in 16 centres in Brazil. Participants received two doses of vaccine (3 μg in 0.5 mL) vaccine or placebo at day 0 and 14. The primary efficacy endpoint was the number of symptomatic COVID-19 cases confirmed by RT-PCR 14 days after the second dose of the vaccine. Prevention of disease severity was a major secondary efficacy endpoint, and adverse events incidence up to seven days after immunization was the primary safety outcome. The trial was registered at ClinicalTrials.gov, NCT04456595.

Findings: Between July 21 and Dec 16, 2020, 12 396 participants were enrolled and received at least one vaccine or placebo dose. There were 9,823 participants who received the two doses and were followed for at least 14 days and had, therefore, reached the final efficacy analysis. There were 253 confirmed COVID-19 cases in the cohort: 85 cases (11.0/100 person-year) among 4,953 participants in the vaccine group, and 168 cases (22·3/100 person-year) among 4,870 participants in the placebo group. The primary efficacy against symptomatic COVID-19 was 50·7% (95%CI 36·0-62·0). The secondary efficacy against cases requiring assistance (score ≥3) and moderate and severe cases (score ≥4) were 83·7% (95%CI 58·0-93.7) and 100% (95%CI 56·4-100.0) respectively. All 6 cases of severe COVID-19 occurred in the placebo group. The incidence of adverse reactions, which was mainly pain at the administration site, was higher in the vaccine group (77·1%) than in the placebo group (66·4%). There were 67 serious adverse events reported by 64 participants and all were determined to be unrelated to vaccination, including two fatal cases. In a subset of participants, neutralizing antibody assays showed similar seroconversion and geometric mean titres against B.1.128, P.1, and P.2 variants.

Interpretation: A phase 3 clinical trial conducted in healthcare professionals in Brazil demonstrated that the inactivated CoronaVac vaccine has a good safety profile and is efficacious against any symptomatic SARS-CoV-2 infections and highly protective against moderate and severe COVID-19.

Note:
Trial Registration: The trial was registered at ClinicalTrials.gov, NCT04456595.

Funding Statement: Fundação Butantan, Instituto Butantan, and São Paulo Research Foundation - FAPESP (Grants 2020/10127-1 and 2020/06409-1).

Declaration of Interests: Instituto Butantan is non-profit public research institute that is part of the Secretary of Health of the State of São Paulo and acted as sponsor of the study and is Market Authorization Holder of CoronaVac in Brazil under authorization of Sinovac Life Sciences. Ricardo Palacios, Ana Paula Batista, Camila Nascimento Santos Albuquerque, Elizabeth Gonzalez Patiño, Joane do Prado Santos, Mônica Tilli Reis Pessoa Conde and Roberta de Oliveira Piorelli are full-time employees of Fundação Butantan, a non-profit organization supporting activities from Instituto Butantan. Viviane Fongaro Botosso is full-time researcher at Instituto Butantan. None of us received shares or any kind monetary compensation linked to the distribution of CoronaVac in Brazil, or have any share or financial interests in Sinovac Life Sciences or parent companies. The other investigators of the study in Brazil Ana Lúcia Lyrio de Oliveira, André Machado de Siqueira, Cor Jesus Fernandes Fontes, Danise Senna Oliveira, Eduardo Barbosa Coelho, Esper Georges Kallás, Fabiano Ramos, Fábio Eudes Leal, Francisco Hideo Aoki, Gecilmara Cristina Salviato Pileggi, Gustavo Adolfo Sierra Romero, Luis Fernando Aranha Camargo, Luiz Carlos Pereira Junior, Maurício Lacerda Nogueira, Mauro Martins Teixeira, Sonia Mara Raboni, and Danielle Bruna Leal de Oliveira received shares or any kind monetary compensation linked to the distribution of CoronaVac in Brazil, or have any share or financial interests in Sinovac Life Sciences or parent companies. Gang Zeng and Qianqian Xin are full-time employees of Sinovac Biotech Co. Ltd.

Ethic Approval Statement: The study complied with ICH Good Clinical Practices and Brazilian ethical and regulatory guidelines, and was approved by the Brazilian National Research Ethics Council - CONEP - (CAAE 34634620.1.1001.0068) and the Brazilian National Regulatory Agency - ANVISA - (CE 47/2020).

Keywords: Brazil, COVID-19, COVID-19 Vaccine, Inactivated Vaccines, Phase III Clinical Trial, Randomised controlled trial, protocol

Suggested Citation

Palacios, Ricardo and Batista, Ana Paula and Albuquerque, Camila Santos Nascimento and Patiño, Elizabeth González and Santos, Joane do Prado and Tilli Reis Pessoa Conde, Mônica and Piorelli, Roberta de Oliveira and Pereira Júnior, Luiz Carlos and Raboni, Sonia Mara and Ramos, Fabiano and Sierra Romero, Gustavo Adolfo and Leal, Fábio Eudes and Camargo, Luis Fernando Aranha and Aoki, Francisco Hideo and Coelho, Eduardo Barbosa and Oliveira, Danise Senna and Fontes, Cor Jesus Fernandes and Pileggi, Gecilmara Cristina Salviato and Oliveira, Ana Lúcia Lyrio de and Siqueira, André Machado de and Oliveira, Danielle Bruna Leal de and Botosso, Viviane Fongaro and Zeng, Gang and Xin, Qianqian and Teixeira, Mauro Martins and Nogueira, Maurício Lacerda and Kallas, Esper Georges, Efficacy and Safety of a COVID-19 Inactivated Vaccine in Healthcare Professionals in Brazil: The PROFISCOV Study (April 11, 2021). Available at SSRN: https://ssrn.com/abstract=3822780 or http://dx.doi.org/10.2139/ssrn.3822780

Ricardo Palacios (Contact Author)

Instituto Butantan ( email )

Avenida Vital Brasil, 1500
Sao Paulo, SP 05503-900
Brazil
05503-900 (Fax)

Ana Paula Batista

Instituto Butantan ( email )

Avenida Vital Brasil, 1500
Sao Paulo, SP 05503-900
Brazil

Camila Santos Nascimento Albuquerque

affiliation not provided to SSRN

Elizabeth González Patiño

affiliation not provided to SSRN

Joane do Prado Santos

Instituto Butantan ( email )

Avenida Vital Brasil, 1500
Sao Paulo, SP 05503-900
Brazil

Mônica Tilli Reis Pessoa Conde

Instituto Butantan ( email )

Avenida Vital Brasil, 1500
Sao Paulo, SP 05503-900
Brazil

Roberta de Oliveira Piorelli

Instituto Butantan ( email )

Avenida Vital Brasil, 1500
Sao Paulo, SP 05503-900
Brazil

Luiz Carlos Pereira Júnior

Institute of Infectious Diseases Emilio Ribas ( email )

Brazil

Sonia Mara Raboni

Federal University of Paraná - Virology Laboratory ( email )

Rua XV de Novembro
1299 - Centro
Curitiba - PR, 80060-000
Brazil

Fabiano Ramos

Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) - School of Medicine ( email )

Brazil

Gustavo Adolfo Sierra Romero

Universidade de Brasília (UnB) ( email )

Campus Universitário Darcy Ribeiro
Asa Norte
Brasília, Distrito Federal 70910-900
Brazil

Fábio Eudes Leal

Universidade Municipal de São Caetano do Sul (USCS) ( email )

Rua Santo Antônio, 50
São Caetano do Sul, São Paulo 09521-160
Brazil

Luis Fernando Aranha Camargo

Hospital Israelita Albert Einstein ( email )

Brazil

Francisco Hideo Aoki

Universidade Estadual de Campinas (UNICAMP) ( email )

Cidade Universitária Zeferino Vaz - Barão
Geraldo
Campinas - SP, 13083-970
Brazil

Eduardo Barbosa Coelho

University of São Paulo (USP) - Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo ( email )

Av. do Café, s/n - Jd. Monte Alegre
Ribeirão Preto, São Paulo 14040900
Brazil

Danise Senna Oliveira

Federal University of Pelotas (UFPel) ( email )

Pelotas, Rio Grande do Sul, RS
Brazil

Cor Jesus Fernandes Fontes

Universidade Federal de Mato Grosso ( email )

Av. Fernando Corrêa da Costa, nº 2367
Bairro Boa Esperança
Cuiabá, MT Mato Grosso 78060-900
Brazil

Gecilmara Cristina Salviato Pileggi

affiliation not provided to SSRN

Ana Lúcia Lyrio de Oliveira

Universidade Federal de Mato Grosso do Sul ( email )

Brazil

André Machado de Siqueira

Evandro Chagas National Institute of Infectious Diseases (INI), FIOCRUZ ( email )

Av. Brasil 4365
Rio de Janeiro, 21040-360
Brazil

Danielle Bruna Leal de Oliveira

University of São Paulo (USP) ( email )

Av. Prof. Luciano Gualberto 380
Sao Paulo, 05508-010
Brazil

Viviane Fongaro Botosso

Instituto Butantan ( email )

Avenida Vital Brasil, 1500
Sao Paulo, SP 05503-900
Brazil

Gang Zeng

Sinovac Life Sciences ( email )

Beijing, 100085
China

Qianqian Xin

Sinovac Life Sciences ( email )

Beijing, 100085
China

Mauro Martins Teixeira

Federal University of Minas Gerais (UFMG) ( email )

Av. Antonio Carlos, 6627
Belo Horizonte, Minas Gerais 31270-901
Brazil

Maurício Lacerda Nogueira

Faculdade de Medicina de São José de Rio Preto (FAMERP) ( email )

São José de Rio Preto, SP
Brazil

Esper Georges Kallas

University of São Paulo (USP) ( email )

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
14,276
Abstract Views
62,628
rank
296
PlumX Metrics