Selected Grantee Publications
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- 8 results found
- niaid
- COVID-19/Coronavirus
- 2022
Gut Microbiome Dysbiosis in Antibiotic-Treated COVID-19 Patients Is Associated with Microbial Translocation and Bacteremia
Bernard-Raichon et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-022-33395-6
The investigators demonstrated that SARS-CoV-2 infection induced gut microbiome dysbiosis in male mice. Samples collected from human COVID-19 patients of both sexes also revealed substantial gut microbiome dysbiosis. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicated that bacteria might translocate from the gut into the systemic circulation of COVID-19 patients. These results were consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19. Supported by ORIP (S10OD021747), NCI, NHLBI, NIAID, and NIDDK.
Distinct Sensitivities to SARS-CoV-2 Variants in Vaccinated Humans and Mice
Walls et al., Cell Reports. 2022.
https://www.doi.org/10.1016/j.celrep.2022.111299
Emergence of SARS-CoV-2 variants necessitates real-time evaluation of their impact on serum neutralizing activity, as a proxy for vaccine efficacy, to inform public health policies and guide vaccine development. The investigators report that vaccinated female BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses toward the SARS-CoV-2 Beta and Gamma variants of concern, compared with humans of both sexes and male nonhuman primates (i.e., rhesus and pigtail macaques). This finding was consistent across several vaccine modalities, doses, antigens, and assays, suggesting caution should be exercised when interpreting serum neutralizing data obtained from mice. Supported by ORIP (P51OD010425, U42OD011123) and NIAID.
Wastewater Sequencing Reveals Early Cryptic SARS-CoV-2 Variant Transmission
Karthikeyan et al., Nature. 2022.
https://www.doi.org/10.1038/s41586-022-05049-6
The investigators explored the use of SARS-CoV-2 RNA concentration in wastewater as a practical approach to estimate community prevalence of COVID-19, detect emerging variants, and track regional infection dynamics. Two obstacles must be overcome to leverage wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. The investigators developed and deployed improved virus concentration protocols and deconvolution software to fully resolve multiple virus strains from wastewater. Results indicate that emerging variants of concern were detected up to 14 days earlier in wastewater samples, and multiple instances of virus spread that were not captured by clinical genomic surveillance were identified by wastewater-based genomic surveillance. The study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. The work suggests a critical, urgently needed methodology for early detection of emerging variants and early public health interventions. Supported by ORIP (S10OD026929), and NIAID.
Durable Protection Against the SARS-CoV-2 Omicron Variant Is Induced by an Adjuvanted Subunit Vaccine
Arunachalam et al., Science Translational Medicine. 2022.
https://www.doi.org/10.1126/scitranslmed.abq4130
Additional SARS-CoV-2 vaccines are needed, owing to waning immunity to the original vaccines and the emergence of variants of concern. A recent study in male rhesus macaques demonstrated 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, an oil-in-water emulsion containing α‑tocopherol. Two immunizations with the vaccine resulted in durable immunity, without cross-reactivity. Further boosting with a version of the vaccine containing the Beta variant or the ancestral RBD elicited cross-reactive immune responses that conferred protection against Omicron challenge. Supported by ORIP (P51OD011104), NCI, and NIAID.
Mosaic RBD Nanoparticles Protect Against Challenge by Diverse Sarbecoviruses in Animal Models
Cohen et al., Science. 2022.
https://www.doi.org/10.1126/science.abq0839
Two animal coronaviruses from the SARS-like betacoronavirus (sarbecovirus) lineage—SARS-CoV and SARS-CoV-2—have caused epidemics or pandemics in humans during the past 20 years. New SARS-CoV-2 variants have prolonged the COVID-19 pandemic, and the discovery of diverse sarbecoviruses in bats raises the possibility of another coronavirus pandemic. Vaccines and therapeutics are needed to protect against both SARS-CoV-2 variants and zoonotic sarbecoviruses with the potential to infect humans. The authors designed mosaic-8 nanoparticles (SARS-CoV-2 and seven animal sarbecoviruses) that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. Their results of immune responses elicited by mosaic-8 RBD nanoparticles in mice and macaques suggest that mosaic nanoparticles could protect against both SARS-CoV-2 variants and zoonotic sarbecoviruses with the potential to infect humans. Supported by ORIP (P40OD012217, U42OD021458, S10OD028685) and NIAID.
CAR/CXCR5–T Cell Immunotherapy Is Safe and Potentially Efficacious in Promoting Sustained Remission of SIV Infection
Pampusch et al., PLOS Pathogens. 2022.
https://www.doi.org/10.1371/journal.ppat.1009831
HIV and simian immunodeficiency virus (SIV) replication are concentrated within the B cell follicles of secondary lymphoid tissues. In this study, the researchers developed immunotherapeutic chimeric antigen receptor (CAR) T cells that home to follicles and clear SIV-infected cells in a rhesus macaque model. The CAR T cells localized to the follicle, replicated, and interacted directly with infected cells. Most of the treated animals maintained lower viral loads in the blood and follicles, compared to control animals. These findings demonstrate the safety and potential efficacy of this immunotherapy approach for long-term remission of HIV without requiring the lifelong use of antiretroviral therapy. Supported by ORIP (P51OD011106), NIAID, and NHLBI.
Protection from SARS-CoV-2 Delta One Year After mRNA-1273 Vaccination in Rhesus Macaques Coincides with Anamnestic Antibody Response in the Lung
Gagne et al., Cell. 2022.
https://www.sciencedirect.com/science/article/pii/S0092867421014057?via%3Dihub=
Efficacy of the vaccine mRNA-1273 against SARS-CoV-2 Delta decreases with time, yet there are limited data on how durability of immune responses affects protection. Researchers immunized male rhesus macaques with mRNA-1273 and challenged them with Delta one year later. Serum neutralizing antibody responses to Delta and protection in upper airway were low one year after mRNA-1273 vaccination. However, mRNA-1273 provided durable protection against Delta in the lower airway and against severe lung disease one year after vaccination, likely through anamnestic induction of antibody responses in the lung. These findings highlight the importance of booster shots for sustained upper and lower airway protection. Supported by ORIP (P51OD011132) and NIAID.
Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial
Gilbert et al., Science. 2022.
https://pubmed.ncbi.nlm.nih.gov/34812653/
Investigators determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna coronavirus efficacy phase 3 clinical trial. Vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines. Supported by ORIP (S10OD028685).