23 Pág.While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential.This research was supported by La Caixa Banking Foundation grant CF01-00008, Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency grant PID2020-117425RB-C22, Fondo COVID-19 grant COV20/00151 (Spanish Health Ministry and Instituto de Salud Carlos III), CSIC grant 2020E84 and Ferrovial donations (to ME). AcknowledgmentsPeer reviewe

Del Val, Margarita

Esteban, Mariano

Gómez, Carmen Elena

López-Bravo, María

Marcos-Villar, Laura

Perdiguero, Beatriz

Ramos, Manuel

Sin, Laura

Sorzano, Carlos Óscar S.

Sánchez-Cordón, Pedro J.

Valverde, José Ramón

Zamora, Carmen

Álvarez, Enrique

Frontiers in Immunology

23 Pág.Introduction: While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential.

Methods: In an effort to develop an immunogen with the capacity to induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions of SARS-CoV-2 structural proteins associated with long-term immunity, termed CoV2-BMEP. Here we describe the characterization, immunogenicity and efficacy of CoV2-BMEP using two delivery platforms: nucleic acid DNA and attenuated modified vaccinia virus Ankara (MVA).

Results: In cultured cells, both vectors produced a main protein of about 37 kDa as well as heterogeneous proteins with size ranging between 25-37 kDa. In C57BL/6 mice, both homologous and heterologous prime/boost combination of vectors induced the activation of SARS-CoV-2-specific CD4 and CD8 T cell responses, with a more balanced CD8+ T cell response detected in lungs. The homologous MVA/MVA immunization regimen elicited the highest specific CD8+ T cell responses in spleen and detectable binding antibodies (bAbs) to S and N antigens of SARS-CoV-2. In SARS-CoV-2 susceptible k18-hACE2 Tg mice, two doses of MVA-CoV2-BMEP elicited S- and N-specific bAbs as well as cross-neutralizing antibodies against different variants of concern (VoC). After SARS-CoV-2 challenge, all animals in the control unvaccinated group succumbed to the infection while vaccinated animals with high titers of neutralizing antibodies were fully protected against mortality, correlating with a reduction of virus infection in the lungs and inhibition of the cytokine storm.

Discussion: These findings revealed a novel immunogen with the capacity to control SARS-CoV-2 infection, using a broader antigen presentation mechanism than the approved vaccines based solely on the S antigen.This research was supported by La Caixa Banking Foundation grant CF01-00008, Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency grant PID2020-117425RB-C22, Fondo COVID-19 grant COV20/00151 (Spanish Health Ministry and Instituto de Salud Carlos III), CSIC grant 2020E84 and Ferrovial donations (to ME). AcknowledgmentsPeer reviewe

Sánchez-Cordón, P. J.

Val, Margarita del

Gómez, Carmen E.

Digital.CSIC

Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

https://digital.csic.es/bitstream/10261/331922/1/Immunogenicity_and_efficacy_of.pdf

Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

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