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Research Papers

A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease

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Pages 519-527 | Received 27 May 2015, Accepted 26 Jul 2015, Published online: 23 Feb 2016

Figures & data

Table 1. Summary of the vaccines against viral diseases reported that have the viral nucleoprotein as the sole target antigen

Figure 1. IFN-γ ELISpot responses from A129 and 129Sv/Ev mice vaccinated with MVA-NP3010 (black), MVA-1974 (gray) or saline (white). Splenocytes from vaccinated mice were restimulated with peptides derived from the CCHFv nucleoprotein split into 2 pools and summed, or a single pool containing peptides from the tPA and V5 fusion partners. Mean ± SEM is plotted .

Figure 1. IFN-γ ELISpot responses from A129 and 129Sv/Ev mice vaccinated with MVA-NP3010 (black), MVA-1974 (gray) or saline (white). Splenocytes from vaccinated mice were restimulated with peptides derived from the CCHFv nucleoprotein split into 2 pools and summed, or a single pool containing peptides from the tPA and V5 fusion partners. Mean ± SEM is plotted .

Figure 2. Antibody responses from A129 and 129Sv/Ev mice vaccinated with MVA-NP3010. A representative animal from each mouse strain is shown. Sera from vaccinated A129 and 129Sv/Ev mice were tested for reactivity with a baculovirus-expression recombinant CCHFv NP (lane 4) and CCHFv-infected (lane 3) or uninfected (lane 2) SW13 cells by Western blotting. Lane 1 shows a molecular weight marker.

Figure 2. Antibody responses from A129 and 129Sv/Ev mice vaccinated with MVA-NP3010. A representative animal from each mouse strain is shown. Sera from vaccinated A129 and 129Sv/Ev mice were tested for reactivity with a baculovirus-expression recombinant CCHFv NP (lane 4) and CCHFv-infected (lane 3) or uninfected (lane 2) SW13 cells by Western blotting. Lane 1 shows a molecular weight marker.

Figure 3. IFN-γ ELISpot responses from A129 mice vaccinated with MVA-NP10200, MVA-1974 or saline. Splenocytes from vaccinated mice were restimulated with peptides derived from the CCHFv nucleoprotein split into 2 pools and summed, or a single pool containing peptides from the tPA and V5 proteins. Black, white and gray bars denote animals given saline, MVA-1974 and MVA-NP, respectively. Mean ± SEM is plotted.

Figure 3. IFN-γ ELISpot responses from A129 mice vaccinated with MVA-NP10200, MVA-1974 or saline. Splenocytes from vaccinated mice were restimulated with peptides derived from the CCHFv nucleoprotein split into 2 pools and summed, or a single pool containing peptides from the tPA and V5 proteins. Black, white and gray bars denote animals given saline, MVA-1974 and MVA-NP, respectively. Mean ± SEM is plotted.

Figure 4. Antibody response from a representative A129 mouse vaccinated with MVA-NP10200. Sera from vaccinated A129 mice were tested for reactivity with a baculovirus-expression recombinant CCHFv NP (lane 4) and CCHFv-infected (lane 3) or uninfected (lane 2) SW13 cells by Western blotting. Lane 1 shows a molecular weight marker.

Figure 4. Antibody response from a representative A129 mouse vaccinated with MVA-NP10200. Sera from vaccinated A129 mice were tested for reactivity with a baculovirus-expression recombinant CCHFv NP (lane 4) and CCHFv-infected (lane 3) or uninfected (lane 2) SW13 cells by Western blotting. Lane 1 shows a molecular weight marker.

Figure 5. Efficacy of MVA-NP10200 in A129 mice challenged with CCHFv. A129 mice were challenged with double the minimum lethal dose of CCHFv 14 d after booster vaccination with MVA-NP10200 (unfilled squares), MVA-1974 (solid diamonds) or saline (solid circles).

Figure 5. Efficacy of MVA-NP10200 in A129 mice challenged with CCHFv. A129 mice were challenged with double the minimum lethal dose of CCHFv 14 d after booster vaccination with MVA-NP10200 (unfilled squares), MVA-1974 (solid diamonds) or saline (solid circles).

Figure 6. Normalized viral load analysis of CCHFv RNA by RT-PCR. A129 mice were challenged with double the minimum lethal dose of CCHFv, 14 d after booster vaccination with MVA-NP10200 (gray bars) or MVA-1974 (black bars). Four days post-challenge, 3 randomly selected animals from each group were killed humanely and analyzed by RT-PCR for CCHFv gene expression, normalized to mouse HPRT gene expression. Data show mean ± SEM.

Figure 6. Normalized viral load analysis of CCHFv RNA by RT-PCR. A129 mice were challenged with double the minimum lethal dose of CCHFv, 14 d after booster vaccination with MVA-NP10200 (gray bars) or MVA-1974 (black bars). Four days post-challenge, 3 randomly selected animals from each group were killed humanely and analyzed by RT-PCR for CCHFv gene expression, normalized to mouse HPRT gene expression. Data show mean ± SEM.

Table 2. Severity of spleen and liver lesions in challenged mice: distribution in treatment groups