SHIV-C109p5 NHP induces rapid disease progression in elderly macaques with extensive GI viral replication.

CCR5-tropic simian/human immunodeficiency viruses (SHIV) with clade C transmitted/founder envelopes represent a critical tool for the investigation of HIV experimental vaccines and microbicides in nonhuman primates, although many such isolates lead to spontaneous viral control post infection. Here, we generated a high-titer stock of pathogenic SHIV-C109p5 by serial passage in two rhesus macaques (RM) and tested its virulence in aged monkeys. The co-receptor usage was confirmed before infecting five geriatric rhesus macaques (four female and one male). Plasma viral loads were monitored by reverse transcriptase-quantitative PCR (RT-qPCR), cytokines by multiplex analysis, and biomarkers of gastrointestinal damage by enzyme-linked immunosorbent assay. Antibodies and cell-mediated responses were also measured. Viral dissemination into tissues was determined by RNAscope. Intravenous SHIV-C109p5 infection of aged RMs leads to high plasma viremia and rapid disease progression; rapid decrease in CD4+ T cells, CD4+CD8+ T cells, and plasmacytoid dendritic cells; and wasting necessitating euthanasia between 3 and 12 weeks post infection. Virus-specific cellular immune responses were detected only in the two monkeys that survived 4 weeks post infection. These were Gag-specific TNFα+CD8+, MIP1ß+CD4+, Env-specific IFN-γ+CD4+, and CD107a+ T cell responses. Four out of five monkeys had elevated intestinal fatty acid binding protein levels at the viral peak, while regenerating islet-derived protein 3α showed marked increases at later time points in the three animals surviving the longest, suggesting gut antimicrobial peptide production in response to microbial translocation post infection. Plasma levels of monocyte chemoattractant protein-1, interleukin-15, and interleukin-12/23 were also elevated. Viral replication in gut and secondary lymphoid tissues was extensive.IMPORTANCESimian/human immunodeficiency viruses (SHIV) are important reagents to study prevention of virus acquisition in nonhuman primate models of HIV infection, especially those representing transmitted/founder (T/F) viruses. However, many R5-tropic SHIV have limited fitness in vivo leading to many monkeys spontaneously controlling the virus post acute infection. Here, we report the generation of a pathogenic SHIV clade C T/F stock by in vivo passage leading to sustained viral load set points, a necessity to study pathogenicity. Unexpectedly, administration of this SHIV to elderly rhesus macaques led to extensive viral replication and fast disease progression, despite maintenance of a strict R5 tropism. Such age-dependent rapid disease progression had previously been reported for simian immunodeficiency virus but not for R5-tropic SHIV infections.

Bacterial community composition in the Northern Gulf of Mexico intertidal sediment bioturbated by the ghost shrimp Lepidophthalmus louisianensis.

Bioturbation plays an important role in structuring microbial communities in coastal sediments. This study investigates the bacterial community composition in sediment associated with the ghost shrimp Lepidophthalmus louisianensis at two locations in the Northern Gulf of Mexico (Bay St. Louis, MS, and Choctawhatchee Bay, FL). Bacteria were analysed for shrimp burrows and for three different depths of bioturbated intertidal sediment, using second-generation sequencing of the 16S rRNA gene. Burrow walls held a unique bacterial community, which was significantly different from those in the surrounding sediment communities. Communities in burrow walls and surrounding sediment communities also differed between the two geographic locations. The burrow wall communities from both locations were more similar to each other than to sediment communities from same location. Alpha- and Gammaproteobacteria were more abundant in burrows and surface sediment than in the subsurface, whereas Deltaproteobacteria were more abundant in burrows and subsurface sediment, suggesting sediment mixing by the bioturbator. However, abundance of individual ASVs was geographic location-specific for all samples. Therefore, it is suggested that the geographic location plays an important role in regional microbial communities distinctiveness. Bioturbation appears to be an important environmental driver in structuring the community around burrows. Sampling was conducted during times of the year and water salinity, tidal regime and temperature were variable, nevertheless the structure microbial communities appeared to remain realatively stable suggesting that these environmental variable played only a minor role.

Durable protection against the SARS-CoV-2 Omicron variant is 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 global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-ß (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.

The effect of lead contamination on bioturbation by Lumbriculus variegatus in a freshwater microcosm.

The present study investigated the effect of lead (Pb) on bioturbation by the oligochaete worm Lumbriculus variegatus, using freshwater microcosms. The experiment used lead at "0", 140, 700, and 3500 µg/g in sediment, and used two different laboratory populations of L. variegatus. A molecular genetic analysis and bioassays were conducted to determine if the two populations differed genetically and whether they differed in Pb-sensitivity. The bioturbation of L. variegatus was estimated using luminophores placed at the sediment-water interface at the beginning of the experiment. After the 14 d experiment the luminophore profiles in sediment were used to estimate the biodiffusion and bioadvection coefficients, using the diffusion-advection model. The results showed that the biodiffusion and bioadvection coefficients were generally negatively related to the Pb concentrations in the sediment. Lead at 700 and 3500 µg/g reduced both coefficients, while Pb at 140 µg/g did not. Luminophore profiles in the "0" and 140 µg/g treatments were indicative of a non-local transport, while a diffusive transport was observed at the higher Pb levels. The two laboratory populations of L. variegatus used in the experiment differed in their sensitivity to Pb when mortality was used as the endpoint, but they did not differ in sediment bioturbation or the Pb-sensitivity of this process. Moreover, the genetic analysis did not detect any genetic differences between the populations. This study demonstrated that elevated levels of Pb can impact ecosystem functioning by decreasing the bioturbation activity of benthic organisms such as L. variegatus.