Infection and protection responses of deletion mutants of non-structural proteins of foot-and-mouth disease virus serotype Asia1 in guinea pigs
The development of a negative marker vaccine against the foot-and-mouth disease virus (FMDV) will enhance the capabilities to differentiate vaccinated from infected animals and move forward in the progressive control pathway for the control of FMD. Here, we report the development of mutant FMDV o...
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Published in | Applied microbiology and biotechnology Vol. 106; no. 1; pp. 273 - 286 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
2022
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: |
The development of a negative marker vaccine against the foot-and-mouth disease virus (FMDV) will enhance the capabilities to differentiate vaccinated from infected animals and move forward in the progressive control pathway for the control of FMD. Here, we report the development of mutant FMDV of Asia1 with partial deletion of non-structural proteins 3A and 3B and characterization of their infectivity and protection response in the guinea pig model. The deleted FMDV Asia1/IND/63/1972 mutants, pAsia
Δ3A
and pAsia
Δ3A3B1
were constructed from the full-length infectious clone pAsia
WT
, the viable virus was rescued, and the genetic stability of the mutants was confirmed by 20 monolayer passages in BHK21 cells. The mutant Asia1 viruses showed comparable growth pattern and infectivity with that of Asia
WT
in the cell culture. However, the Asia
Δ3A3B1
virus showed smaller plaque and lower virus titer with reduced infectivity in the suckling mice. In guinea pigs, the Asia
Δ3A3B1
virus failed to induce the disease, whereas the Asia
Δ3A
virus induced typical secondary lesions of FMD. Vaccination with inactivated Asia1 mutant viruses induced neutralizing antibody response that was significantly lower than that of the parent virus on day 28 post-vaccination (dpv) in guinea pigs (
P
< 0.05). Furthermore, challenging the vaccinated guinea pigs with the homologous vaccine strain of FMDV Asia1 conferred complete protection. It is concluded that the mutant Asia
Δ3A3B1
virus has the potential to replace the wild-type virus for use as a negative marker vaccine after assessing the vaccine worth attributes in suspension cell and protective efficacy study in cattle.
Key points
•
Deletion mutant viruses of FMDV Asia1, developed by PCR-mediated mutagenesis of NSP 3A and 3B1, were genetically stable.
•
The growth kinetics and antigenic relatedness of the mutant viruses were comparable with that of the wild-type virus.
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Vaccination of guinea pigs with the deletion mutant viruses conferred complete protection upon challenge with the homologous virus. |
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ISSN: | 0175-7598 1432-0614 |
DOI: | 10.1007/s00253-021-11692-2 |