bioRxiv Science⌕ Search

Biology subjects

Ashraf, U.

Publications and source records attributed to Ashraf, U..

5 recordsLinked to original sources

Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-{beta} (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3x107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.

immunology↗

Zika virus causes placental pyroptosis and associated adverse fetal outcomes by activating GSDME

Zika virus (ZIKV) can be transmitted from mother to fetus during pregnancy, causing adverse fetal outcomes. Several studies have indicated that ZIKV can damage the fetal brain directly; however, whether the ZIKV-induced maternal placental injury contribute to adverse fetal outcomes are sparsely defined. Here, we discovered that ZIKV causes the pyroptosis of placental cells by activating the executor Gasdermin E (GSDME) in vitro and in vivo. Mechanistically, caspase-8 undergoes activation upon the recognition of 5 untranslated region of viral RNA by RIG-I, followed by the stimulation of caspase-3 to ultimately escalate the GSDME cleavage. Further analyses revealed that the ablation of GSDME in ZIKV-infected pregnant mice attenuates placental pyroptosis, which consequently confers protection against adverse fetal outcomes. In conclusion, our study unveils a novel mechanism of ZIKV-induced adverse fetal outcomes via causing placental cell pyroptosis, which could be employed for developing new therapies for ZIKV-associated diseases. Significance statementSeveral studies have elucidated the link between ZIKV infection and congenital ZIKV syndroms (CZS), but the pathogenesis yet needs further study. Here, we reported a novel pathogenic mechanism of ZIKV which leads to pyroptosis of placental cells through activating the pyroptotic executor GSDME, rather than GSDMD. Upon ZIKV infection, GSDME-mediated pyroptosis damages the structure and function of the placenta, thereby affecting the development of the fetus and contributing to the adverse fetal outcomes. Our study highlights the importance of pyroptotic executor GSDME in regulate ZIKV pathogenicity and further confirms that placental injury caused by ZIKV infection is a key factor for CZS.

microbiology↗

Geographic potential of the world largest hornet, Vespa mandarinia Smith (Hymenoptera: Vespidae), worldwide and particularly in North America

The Asian giant hornet (AGH, Vespa mandarinia) is the worlds largest hornet, occurring naturally in the Indomalayan region, where it is a voracious predator of pollinating insects including honey bees. In September 2019, a nest of Asian giant hornets was detected outside of Vancouver, British Columbia and in May 2020 an individual was detected nearby in Washington state, indicating that the AGH successfully overwintered in North America. Because hornets tend to spread rapidly and become pests, reliable estimates of the potential invasive range of V. mandarinia in North America are needed to assess likely human and economic impacts, and to guide future eradication attempts. Here, we assess climatic suitability for AGH in North America, and suggest that, without control, this species could establish populations across the Pacific Northwest and much of eastern North America. Predicted suitable areas for AGH in North America overlap broadly with areas where honey production is highest, as well as with species-rich areas for native bumble bees and stingless bees of the genus Melipona in Mexico, highlighting the economic and environmental necessity of controlling this nascent invasion.

ecology↗

Individual and concurrent effects of drought and chilling stresses on morpho-physiological characteristics and oxidative metabolism of maize cultivars

Maize belongs to tropical environment and is extremely sensitive to drought and chilling stress, particularly at early developmental stages. The present study investigated the individual and combine effects of drought (15% PEG-Solution) and chilling stress (15{degrees}C/12{degrees}C) on the morpho-physiological growth, osmolyte accumulation, production and regulations of reactive oxygen species (ROS) and the activities of antioxidants in two maize hybrids i.e., XD889 and XD319 and two inbred cultivars i.e., Yu13 and Yu37. Individual and combined drought and chilling stresses stimulated the production of O2{square}, H2O2, OH{square} and enhanced malondialdehyde (MDA) contents which led to reduced photosynthetic pigments and morphological growth. Drought, chilling and drought + chilling stress conditions induced the compatible osmolytes, ROS detoxifying proteins and antioxidants to counterbalanced the oxidative damage. It was found that the concurrent occurrence of drought + chilling stress was more lethal for maize seedling growth than the drought and chilling individual stresses. However, the performance of hybrid maize cultivars (XD889 and XD319) was better than the inbred maize cultivars (Yu13 and Yu37). For improving tolerance to individual and concurrent drought and chilling stress in maize, future research focus should be on developing genetically engineer plants that have the ability to generate specific response against sub-optimal temperature and water deficit conditions.

plant biology↗

Mixed-cropping systems of different rice cultivars have grain yield and quality advantages over mono-cropping systems

Mixed-cropping system is a centuries-old cropping technique that is still widely practiced in the farmers field over the globe. Increased plant diversity enhances farmland biodiversity, which would improve grain yield and quality; however, the impacts of growing different rice cultivars simultaneously were rarely investigated. In present study, five popular rice cultivars were selected and ten mixture combinations were made according to the growth period, plant height, grain yield and quality, and pest and disease resistance. Seedlings of the five cultivars and ten mixture combinations (mixed-sowing of the seeds in an equal ratio, then mixed-transplanting and finally mixed-harvesting) were grown in plastic pots under greenhouse during the early and late growing seasons in 2016. Results showed that, compared with the corresponding mono-cropping systems, almost all combinations of the mixed-cropping systems have advantages in yield related traits and grain quality. Compared with the mono-cropping systems in the early and late growing seasons in 2016, mixed-cropping systems increased the number of spikelets per panicle, seed-setting rate, and grain weight per pot and harvest index by 19.52% and 5.77%, 8.53% and 4.41%, 8.31% and 4.61%, and 10.26% and 6.98%, respectively (paired t-test). In addition, mixed-cropping systems reduced chalky rice rate and chalkiness degree by 33.12% and 43.42% and by 30.11% and 48.13% in the early and late growing seasons, respectively (paired t-test). These results may be due to enhanced SPAD indexes and photosynthetic rates at physiology maturity in mixed-cropping systems. In general, it was found that mixed-cropping with different rice cultivars have potential for increasing grain yield and improving grain quality.

ecology↗