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. 2007 Oct;76(5):1131-6.
doi: 10.1007/s00253-007-1073-y. Epub 2007 Jun 21.

Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus

Lei Ba  1 , Christopher E Yi, Linqi Zhang, David D Ho, Zhiwei Chen
Affiliations

Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus

Lei Ba et al. Appl Microbiol Biotechnol. 2007 Oct.

Abstract

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (CoV), SARS-CoV. In previous studies, we showed that a SARS-CoV spike (S) glycoprotein-based modified vaccinia Ankara (MVA-S) vaccine could induce strong neutralizing antibody (Nab) response which might have played a critical role in protecting Chinese rhesus monkeys from the pathogenic viral challenge. To date, however, it remains unknown what the minimal level of Nab is required to achieve sterile immunity in humans. It is therefore important to explore techniques to maximize the level of Nab response in vivo. Here, we evaluate various vaccination regimens using combinations of DNA-S, MVA-S, and adenovirus type 5 (Ad5-S) vaccines. We show that in vaccinated mice and rabbits, a heterologous MVA-S prime with Ad5-S boost regimen induces the highest and most persistent level of Nab response when compared with other combinations. Interestingly, the initial level of Nab after prime does not necessarily predict the magnitude of the secondary response after the boost. Thus, our data provides a promising optimal regimen for vaccine development in humans against SARS-CoV infection.

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Figures

Fig. 1
Fig. 1
Nab response in mice that were primed with DNA-S, MVA-S, or Ad5-S vaccines. Three mice as a group were tested for each vaccine. The average values of each test group and the standard error bars are presented. This neutralization experiment was repeated three times with consistent results obtained
Fig. 2
Fig. 2
Nab response in mice after the boost immunization with DNA-S, MVA-S, or Ad5-S vaccines. The letters present different combination of vaccinations: DD for DNA-S prime and DNA-S boost; MM for MVA-S prime and MVA-S boost; AA for Ad5-S prime and Ad5-S boost; DM for DNA-S prime and MVA-S boost; AM for Ad5-S prime and MVA-S boost; MA for MVA-S prime and AD5-S boost; and DA for DNA-S prime and AD5-S boost. Three mice as a group were tested for each vaccine. The average values of each test group and the standard error bars are presented. This neutralization experiment was repeated three times with consistent results obtained
Fig. 3
Fig. 3
Nab response in rabbits that were primed with MVA-S or Ad5-S vaccines. Three rabbits as a group were tested for each vaccine. The average values of each test group and the standard error bars are presented. This neutralization experiment was repeated three times with consistent results obtained
Fig. 4
Fig. 4
Nab response in rabbits after the boost immunization with MVA-S or Ad5-S vaccines. The letters present different combination of vaccinations: AM for Ad5-S prime and MVA-S boost regimen; AA for Ad5-S prime and Ad5-S boost regimen; and MA for MVA-S prime and AD5-S boost regimen. Three rabbits as a group were tested for each regimen. The average values of each test group and the standard error bars are presented. This Nab experiment was repeated three times with consistent results obtained
Fig. 5
Fig. 5
Persistent Nab response after the boost immunization with MVA-S or Ad5-S vaccines in rabbits. The x-axis represents the time following boost immunization. The y-axis indicates the serum dilution titer when IC50 (a) or IC90 (b) was achieved. Three rabbits as a group were tested for each vaccine regimen. The average values of each test group and the standard error bars are presented. The neutralization assay was repeated three times with consistent results obtained
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