English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Two recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1) mutant viruses have been developed, using a reverse genetics system, for evaluation as potential intranasal vaccine candidates. These rHPIV1 vaccine candidates have two non-temperature sensitive (non- ts ) attenuating ( att ) mutations primarily in the P/C gene, namely C R84G HN T553A  (two point mutations used together as a set) and C Δ170  (a short deletion mutation), and two  ts att  mutations in the L gene, namely L Y942A  (a point mutation), and L Δ1710–11  (a short deletion), the last of which has not been previously described. The latter three mutations were specifically designed for increased genetic and phenotypic stability. These mutations were evaluated on the HPIV1 backbone, both individually and in combination, for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs).    Results  The rHPIV1 mutant bearing the novel L Δ1710–11  mutation was highly  ts  and attenuated in AGMs and was immunogenic and efficacious against HPIV1 wt challenge. The rHPIV1-C R84G/Δ170 HN T553A L Y942A  and rHPIV1-C R84G/Δ170 HN T553A L Δ1710–11  vaccine candidates were highly  ts , with shut-off temperatures of 38°C and 35°C, respectively, and were highly attenuated in AGMs. Immunization with rHPIV1-C R84G/Δ170 HN T553A L Y942A  protected against HPIV1 wt challenge in both the upper and lower respiratory tracts. In contrast, rHPIV1-C R84G/Δ170 HN T553A L Δ1710–11  was not protective in AGMs due to over-attenuation, but it is expected to replicate more efficiently and be more immunogenic in the natural human host.    Conclusion  The rHPIV1-C R84G/Δ170 HN T553A L Y942A  and rHPIV1-C R84G/Δ170 HN T553A L Δ1710–11  vaccine candidates are clearly highly attenuated in AGMs and clinical trials are planned to address safety and immunogenicity in humans.

Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes