The combined vaccination protocol of DNA/MVA expressing Zika virus structural proteins as efficient inducer of T and B cell immune responses

Abstract

Zika virus (ZIKV) is a is a mosquito-borne pathogen with public health importance due to the high risk of its mosquito vector dissemination and the severe neurological and teratogenic sequelae associated with infection. Vaccines with broad immune specificity and control against this re-emerging virus are needed. Here, we described that mice immunized with a priming dose of a DNA plasmid mammalian expression vector encoding ZIKV prM-E antigens (DNA-ZIKV) followed by a booster dose of a modified vaccinia virus Ankara (MVA) vector expressing the same prM-E ZIKV antigens (MVA-ZIKV) induced broad, polyfunctional and long-lasting ZIKV-specific CD4 + and CD8 + T-cell immune responses, with high levels of CD4 + T follicular helper cells, together with the induction of neutralizing antibodies. All those immune parameters were significantly stronger in the heterologous DNA-ZIKV/MVA-ZIKV immunization group compared to the homologous prime/boost immunizations regimens. Collectively, these results provided an optimized immunization protocol able to induce high levels of ZIKV-specific T-cell responses, as well as neutralizing antibodies and reinforce the combined use of DNA-based vectors and MVA-ZIKV as promising prophylactic vaccination schedule against ZIKV.

Low Immune Cross-Reactivity between West Nile Virus and a Zika Virus Vaccine Based on Modified Vaccinia Virus Ankara

“…We have previously shown that a ZIKV vaccine candidate based on the highly attenuated poxvirus MVA expressing ZIKV prM and E structural proteins (MVA-ZIKV) induced a robust specific protective immune response against ZIKV infection in mouse models [ 23 , 24 ]. Here, we have further evaluated in vivo the consequences of the potential cross-reactivity between vaccination with MVA-ZIKV and the subsequent infection with WNV in a mouse model for WNV infection.…”

“…The origin and procedures for amplification in chicken embryo fibroblasts (CEF) and titration of attenuated MVA-WT and recombinant MVA-ZIKV viruses have been previously described [ 23 , 24 ]. WNV NY99 (GenBank accession KC407666.1) was produced and titrated in Vero CCL81 cells (ATCC) by plaque assay in standard agarose semisolid medium, as previously described [ 8 ].…”

“…Similarly, no statistically significant differences in mice survival upon WNV challenge were noticed regardless of the immunogen administered (Figure 1C). models [23,24]. Here, we have further evaluated in vivo the consequences of the potential cross-reactivity between vaccination with MVA-ZIKV and the subsequent infection with WNV in a mouse model for WNV infection.…”

“…Thus, anticipating the potential scenario of emergency vaccination against ZIKV in areas where WNV is circulating, such as some parts of Europe and the Mediterranean Basin, we have evaluated the cross-reactivity between our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (termed MVA-ZIKV) [ 23 , 24 ] and WNV. Our results indicate low cross-reactivity between MVA-ZIKV and WNV and absence of ADE in mouse models.…”

Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

“…All data were collected using BD FACSAria™ III flow cytometer (BD Biosciences, San Jose, CA, USA) and analyzed using FlowJo v10 software (Tree Star). Analysis of polyfunctional T cells was done by Boolean gating using FlowJo software from vaccinated animals, as previously described [ 31 , 32 , 33 ].…”