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

doi:10.1016/j.heliyon.2024.e25539

A polyvalent RNA vaccine reduces the immune imprinting phenotype in mice and induces neutralizing antibodies against omicron SARS-CoV-2

Heliyon. 2024 Feb 6;10(4):e25539. doi: 10.1016/j.heliyon.2024.e25539. eCollection 2024 Feb 29.

Authors

Vinicius Pinto Costa Rocha^{1

2}, Bruna Aparecida Souza Machado^{1

3}, Breno Cardim Barreto², Helenita Costa Quadros^{1

2}, Antonio Márcio Santana Fernandes¹, Eduarda Dos Santos Lima¹, Mariana Evangelista Bandeira¹, Cássio Santana Meira^{1

2}, Larissa Moraes Dos Santos Fonseca¹, Jesse Erasmus⁴, Amit Khandhar⁴, Peter Berglund⁴, Steve Reed⁴, Roberto José da Silva Badaró¹, Milena Botelho Pereira Soares^{1

2}

Affiliations

¹ SENAI Institute of Innovation (ISI) in Health Advanced Systems (CIMATEC ISI SAS), SENAI CIMATEC, Salvador, Bahia, Brazil.
² Gonçalo Moniz Institute, FIOCRUZ, Salvador, Bahia, Brazil.
³ University Center SENAI CIMATEC, Salvador, Bahia, Brazil.
⁴ HDT Biocorp, EUA, Seattle, WA, USA.

Abstract

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.

Keywords: Covid-19; Omicron; Polyvalent vaccine; SARS-CoV-2; Vaccine; mRNA.