A polyvalent RNA vaccine reduces the immune imprinting phenotype in mice and induces neutralizing antibodies against omicron SARS-CoV-2
Vinicius Pinto Costa Rocha,
Bruna Aparecida Souza Machado,
Breno Cardim Barreto,
Helenita Costa Quadros,
Antonio Márcio Santana Fernandes,
Eduarda dos Santos Lima,
Mariana Evangelista Bandeira,
Cássio Santana Meira,
Larissa Moraes dos Santos Fonseca,
Jesse Erasmus,
Amit Khandhar,
Peter Berglund,
Steve Reed,
Roberto José da Silva Badaró,
Milena Botelho Pereira Soares
Affiliations
Vinicius Pinto Costa Rocha
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil; Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, Brazil; Corresponding author. SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil.
Bruna Aparecida Souza Machado
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil; University Center SENAI CIMATEC, Salvador, Bahia, Brazil
Breno Cardim Barreto
Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, Brazil
Helenita Costa Quadros
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil; Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, Brazil
Antonio Márcio Santana Fernandes
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil
Eduarda dos Santos Lima
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil
Mariana Evangelista Bandeira
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil
Cássio Santana Meira
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil; Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, Brazil
Larissa Moraes dos Santos Fonseca
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil
Jesse Erasmus
HDT Biocorp, EUA, Seattle, WA, USA
Amit Khandhar
HDT Biocorp, EUA, Seattle, WA, USA
Peter Berglund
HDT Biocorp, EUA, Seattle, WA, USA
Steve Reed
HDT Biocorp, EUA, Seattle, WA, USA
Roberto José da Silva Badaró
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil
Milena Botelho Pereira Soares
SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil; Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, Brazil; Corresponding author. SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil.
Immune imprinting is now evident in COVID-19 vaccinated people. This phenomenon may impair the development of effective neutralizing antibodies against variants of concern (VoCs), mainly Omicron and its subvariants. Consequently, the boost doses with bivalent vaccines have not shown a significant gain of function regarding the neutralization of Omicron. The approach to design COVID-19 vaccines must be revised to improve the effectiveness against VoCs. Here, we took advantage of the self-amplifying characteristic of RepRNA and developed a polyvalent formulation composed of mRNA from five VoCs. LION/RepRNA Polyvalent induced neutralizing antibodies in mice previously immunized with LION/RepRNA D614G and reduced the imprinted phenotype associated with low neutralization capacity of Omicron B.1.1.529 pseudoviruses. The polyvalent vaccine can be a strategy to handle the low neutralization of Omicron VoC, despite booster doses with either monovalent or bivalent vaccines.
