What question did this study set out to answer?

To determine whether sequential introduction of multiple temperature-sensitive missense mutations into the influenza A PB2 gene creates genetically stable, stepwise-attenuated viruses for live vaccine development.

October 1, 1995Journal of Virology

Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine

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Authors

KSKanta SubbaraoNorthwestern University EPE J ParkNational Institute of Allergy and Infectious Diseases CLC M LawsonMurdoch University

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Implication

Preclinical study reveals that sequential PB2 missense mutations step-wise attenuate influenza A in animal models, indicating a viable rational design strategy for live-attenuated vaccines.

Key Points

To determine whether sequential introduction of multiple temperature-sensitive missense mutations into the influenza A PB2 gene creates genetically stable, stepwise-attenuated viruses for live vaccine development.
Engineered double- and triple-mutant PB2 genes (substituting residues at amino acids 112, 265, 556, and 658) using reverse genetics and rescued them into infectious influenza A viruses.
Assessed in vitro temperature sensitivity, evaluated genetic stability in immunocompromised mice, and tested replication attenuation, immunogenicity, and protective efficacy against wild-type challenge in hamsters.
Transfectant viruses with double and triple mutations exhibited stepwise increases in temperature sensitivity and viral attenuation in hamster lower respiratory tracts compared to single-mutant viruses.
Temperature sensitivity correlated significantly with in vivo attenuation, and the phenotype remained genetically stable in two of three double mutants after prolonged replication in immunocompromised mice.
Intranasal inoculation with triple-mutant viruses stimulated robust serum hemagglutination-inhibiting antibody titers and conferred complete protection against wild-type influenza challenge in hamsters.

Cite This Study

Subbarao et al. (1995) studied this question.

synapsesocial.com/papers/6a9470608a4c78aef331a9d3 https://doi.org/10.1128/jvi.69.10.5969-5977.1995

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Implication

Preclinical study reveals that sequential PB2 missense mutations step-wise attenuate influenza A in animal models, indicating a viable rational design strategy for live-attenuated vaccines.

Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine

Discussion

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Implication

Key Points

Cite This Study

Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine

Discussion

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Implication

Key Points

Cite This Study

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