Recombinant HMPV lacking G or M2-2 proteins were attenuated up to 4,000-fold in the lower respiratory tract of African green monkeys but remained highly immunogenic and protective.
Do recombinant HMPV mutants lacking SH, G, or M2-2 proteins replicate efficiently and provide protective immunity in African green monkeys?
The deltaG and deltaM2-2 HMPV mutants are highly attenuated yet immunogenic in primates, making them promising live-attenuated vaccine candidates.
Recombinant human metapneumovirus (HMPV) in which the SH, G, or M2 gene or open reading frame was deleted by reverse genetics was evaluated for replication and vaccine efficacy following topical administration to the respiratory tract of African green monkeys, a permissive primate host. Replication of the deltaSH virus was only marginally less efficient than that of wild-type HMPV, whereas the deltaG and deltaM2-2 viruses were reduced sixfold and 160-fold in the upper respiratory tract and 3,200-fold and 4,000-fold in the lower respiratory tract, respectively. Even with the highly attenuated mutants, there was unequivocal HMPV replication at each anatomical site in each animal. Thus, none of these three proteins is essential for HMPV replication in a primate host, although G and M2-2 increased the efficiency of replication. Each gene-deletion virus was highly immunogenic and protective against wild-type HMPV challenge. The deltaG and deltaM2-2 viruses are promising vaccine candidates that are based on independent mechanisms of attenuation and are appropriate for clinical evaluation.
Biacchesi et al. (Wed,) conducted a other in Human metapneumovirus (HMPV) infection. Recombinant human metapneumovirus (HMPV) lacking SH, G, or M2-2 protein vs. Wild-type HMPV was evaluated on Replication efficiency in the upper and lower respiratory tract. Recombinant HMPV lacking G or M2-2 proteins were attenuated up to 4,000-fold in the lower respiratory tract of African green monkeys but remained highly immunogenic and protective.