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NiFe-based non-precious-metal catalysts are promising substitutes for noble-metal-based catalysts due to their outstanding electrochemical performance and endurance. Herein, a NiFe-based MOF supported on Ni foam was designed to obtain good OER and HER activities in alkaline media. Thanks to the 3-D hierarchical layer structure distributed on Ni foam, the high exposure of active sites, and the good conductance, as-obtained NiFe-MOF-5 presented advantages for its use in electrochemical catalysis. As a result, an overpotential of 168 mV at 10 mA cm−2 for the OER was reached. Moreover, the catalyst only required a cell voltage of 1.57 V at 10 mA cm−2 for overall water splitting, and it outperformed most previously reported non-precious-metal electrocatalysts in 1 M KOH.

Recent studies have reported the protective efficacy of both natural1 and vaccine-induced2–7 immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques (Macaca mulatta) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8+ T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents. Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2.

Viral rebound following antiretroviral therapy (ART) discontinuation in HIV-1-infected individuals is believed to originate from a small pool of CD4+ T cells harboring replication-competent provirus. However, the origin and nature of the rebound virus has remained unclear. Recent studies have suggested that rebound virus does not originate directly from individual latent proviruses but rather from recombination events involving multiple proviruses. Here we evaluate the origin of rebound virus in 16 ART-suppressed, chronically SIV-infected rhesus monkeys following ART discontinuation. We sequence viral RNA and viral DNA in these animals prior to ART initiation, during ART suppression, and following viral rebound, and we compare rebound viral RNA after ART discontinuation with near full-length viral DNA from peripheral blood and lymph node mononuclear cells (PBMC and LNMC) during ART suppression. Sequences of initial rebound viruses closely match viral DNA sequences in PBMC and LNMC during ART suppression. Recombinant viruses are rare in the initial rebound virus populations but arise quickly within 2–4 weeks after viral rebound. These data suggest that intact proviral DNA in PBMC and LNMC during ART suppression is likely the direct origin of viral rebound in chronically SIV-infected rhesus monkeys following ART discontinuation., The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.

Ad26.COV2.S has demonstrated durability and clinical efficacy against symptomatic COVID-19 in humans. In this study, we report the correlates of durability of humoral and cellular immune responses in 20 rhesus macaques immunized with single-shot Ad26.COV2.S and the immunogenicity of a booster shot at 8 to 10 months after the initial immunization. Ad26.COV2.S elicited durable binding and neutralizing antibodies as well as memory B cells and long-lived bone marrow plasma cells. Innate immune responses and bone marrow plasma cell responses correlated with durable antibody responses. After Ad26.COV2.S boost immunization, binding and neutralizing antibody responses against multiple SARS-CoV-2 variants increased 31- to 69-fold and 23- to 43-fold, respectively, compared with preboost concentrations. Antigen-specific B cell and T cell responses also increased substantially after the boost immunization. Boosting with a modified Ad26.COV2.S.351 vaccine expressing the SARS-CoV-2 spike protein from the beta variant led to largely comparable responses with slightly higher beta- and omicron-specific humoral immune responses. These data demonstrate that a late boost with Ad26.COV2.S or Ad26.COV2.S.351 resulted in a marked increase in humoral and cellular immune responses that were highly cross-reactive across multiple SARS-CoV-2 variants in rhesus macaques.

BackgroundThe rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. Immune correlates of vaccine protection against Omicron are not known.Methods30 cynomolgus macaques were immunized with homologous and heterologous prime-boost regimens with the mRNA-based BNT162b2 vaccine and the adenovirus vector-based Ad26.COV2.S vaccine. Following vaccination, animals were challenged with the SARS-CoV-2 Omicron variant by the intranasal and intratracheal routes.ResultsOmicron neutralizing antibodies were observed following the boost immunization and were higher in animals that received BNT162b2, whereas Omicron CD8+ T cell responses were higher in animals that received Ad26.COV2.S. Following Omicron challenge, sham controls showed more prolonged virus in nasal swabs than in bronchoalveolar lavage. Vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs, showing that current vaccines provide substantial protection against Omicron in this model. However, vaccinated animals that had moderate levels of Omicron neutralizing antibodies but negligible Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Virologic control correlated with both antibody and T cell responses.ConclusionsBNT162b2 and Ad26.COV2.S provided robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in macaques. Protection against this highly mutated SARS-CoV-2 variant correlated with both humoral and cellular immune responses.

The highly mutated SARS-CoV-2 Omicron (B.1.1.529) variant has been shown to evade a substantial fraction of neutralizing antibody responses elicited by current vaccines that encode the WA1/2020 Spike immunogen1, resulting in increased breakthrough infections and reduced vaccine efficacy. Cellular immune responses, particularly CD8+ T cell responses, are likely critical for protection against severe SARS-CoV-2 disease2-6. Here we show that cellular immunity induced by current SARS-CoV-2 vaccines is highly cross-reactive against the SARS-CoV-2 Omicron variant. Individuals who received Ad26.COV2.S or BNT162b2 vaccines demonstrated durable CD8+ and CD4+ T cell responses that showed extensive cross-reactivity against both the Delta and Omicron variants, including in central and effector memory cellular subpopulations. Median Omicron-specific CD8+ T cell responses were 82-84% of WA1/2020-specific CD8+ T cell responses. These data suggest that current vaccines may provide considerable protection against severe disease with the SARS-CoV-2 Omicron variant despite the substantial reduction of neutralizing antibody responses.

In this study, we reported the complete genome of a novel Polerovirus, named Tobacco yellow virus (TYV), which can be transmitted by Myzus persicae. TYV had a single-stranded RNA genome of 5735 nucleotides in length and contained six putative open reading frames (ORFs). Phylogenetic analysis with whole genome nucleotide sequences and amino acid sequences deduced from the conserved domain of the RNA-dependent RNA polymerase, clustered TYV with Potato leafroll virus from the genus Polerovirus with high bootstrap values. However, TYV clustered with Brassica yellow virus using amino acid sequences deduced from the conserved domain of the coat protein. Taken together with the identities between ORFs in TYV and related ORFs in species from Polerovirus, our results strongly suggested TYV is a novel species of the genus Polerovirus.

Summary The bacterial communities in the wound tissues of Pinus massoniana were analysed by 16S rDNA amplicon sequencing. The results showed that the bacterial richness and diversity changed remarkably whether the wound was inoculated with pine wood nematode (PWN; Bursaphelenchus xylophilus) or not after 12 h. However, the predominant bacteria Stenotrophomonas, Burkholderiaceae, Pseudomonas, Serratia and Delftia, introduced by PWN in the wound tissues, changed within 6 h. After 6 h of PWN inoculation, the most abundant genus associating with PWN, Stenotrophomonas, failed to colonise the wound tissues, and the abundance of Delftia decreased, while the other representative bacteria, Burkholderiaceae, Pseudomonas and Serratia, from the PWN were markedly enriched. In addition, our study is the first to report the association of Serratia liquefaciens with PWN. Predicted functional analyses using the Tax4Fun tool showed that the alterations in bacterial composition also led to shifts in their functional pathways, especially after 12 h of PWN inoculation. These findings clarified that the bacteria carried by PWN were responsible for the alterations in bacterial communities in the wound tissues and will shed light on the invasion mechanism of PWN.

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1-8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.

In this paper, AACGS concrete was prepared by using raw and 700 °C calcined coal gangue as the coarse aggregate and alkali-activated coal gangue-slag (AACGS) as the cementitious material. The variation of compressive strength and durability of AACGS concrete was studied, and the durability damage mechanism of AACGS concrete is analyzed in depth by SEM. The research results showed that coal gangue as coarse aggregate shows high compressive strength and good durability in AACGS concrete. AACGS concrete with calcined CGCA shows great advantages in compressive strength and sulfate attack resistance. Under the condition of large content, its long-term frost resistance durability and chloride ion permeability resistance are not as good as that of raw CGCA. If AACGS concrete is applied to the freeze-thaw environment, the content range of CGCA should be 30%–50%. This study provides an experimental basis for the large-scale utilization of coal gangue.

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. 1–3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)4–7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas., Zika virus vaccination elicits Zika and dengue virus cross-neutralizing antibodies in flavivirus-exposed individuals, potentially enhancing the protective efficacy of the vaccine in flavivirus-endemic regions.

The corrosion resistance effects of levofloxacin (LVFX), Ce(NO3)3, and their mixture on AA2024-T4 in 3.5% NaCl solution were investigated using weight-loss method, electrochemical impedance...

The development of low-cost, earth-abundant and highly-efficient cocatalysts is still important to promote the photocatalytic H2 evolution reaction over semiconductors. Herein, a series of Ni nanoclusters (NCs) modified brookite TiO2 quasi nanocubes (BTN) (marked as Ni/BTN) are fabricated via a chemical reduction process. It is found that the loading content and oxidation state of Ni NCs can significantly influence the optical absorption, photocatalytic activity, and stability of Ni/BTN composites. Among the resultant Ni NCs-loaded products, 0.1%Ni/BTN composite delivers the best H2 evolution activity (156 µmol/h), which is 4.3 times higher than that of the BTN alone (36 µmol/h). Furthermore, the Ni NCs with ultrafine size (~2 nm) and high dispersity enable shorter charge transfer distance by quickly capturing the photoexcited electrons of BTN, and thus result in the improved activity even though the oxidization of some Ni NCs on BTN is harmful to the activity for H2 evolution due to the much lower electron capturing capability of NiO than metallic Ni. This study not only clarifies that brookite TiO2 would be a promising high-efficient photo-catalyst for H2 evolution, but also reveals vital clues for further improving its photocatalytic performance using low-cost Ni-based cocatalyst.

The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

The rapid spread of the highly mutated SARS-CoV-2 Omicron variant has raised substantial concerns about the protective efficacy of currently available vaccines. We assessed Omicron-specific humoral and cellular immune responses in 65 individuals who were vaccinated with two immunizations of BNT162b2 and were boosted after at least 6 months with either Ad26.COV2.S (Johnson & Johnson; N=41) or BNT162b2 (Pfizer; N=24) (Table S1).

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice.ImportanceWe have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

The vectors of pinewood nematode of Bursaphelenchus xylophilus (Steiner &amp, Bührer, 1934) are mainly known as xylophagous beetles. Understanding the composition and distribution of these xylophagous beetles in host pine trees infected by PWN is critical to control the spread of PWN. In this study, we investigated the community structures of the xylophagous beetles in two main host trees in Fujian and Shandong, Pinus massoniana Lamb. and Pinus thunbergia Parl., in different stages of infection. All beetles were collected by dissecting the whole pine trees and then identified by their morphological characteristics and COI genes. The results showed that the diversity of xylophagous beetles was different not only between the two host pine trees but also among the different infection stages. The diversity of P. massoniana xylophagous beetles was significantly higher than that of P. thunbergii, and there were also significant differences in the different stages of PWN infection. In total, Scolytinae was the most common (53.70%), followed by Curculionidae (18.26%), Cerambycidae (16.31%), and Cleridae (6.04%). Monochamus alternatus, the most important vector of PWN, occupied a large niche and showed different aggregation positions during the three infection stages in both host trees. This result might be related to the resistance of bark beetles to host trees and competition with other xylophagous beetles. The community diversity of xylophagous beetles was jointly affected by both the infection stages of PWN and the spatial niche of xylophagous beetles. Knowledge of the diversity and competitive relationships among xylophagous beetles might help regulate the population dynamics of these beetles.

Individuals on immunosuppressive (IS) therapy have increased mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and delayed viral clearance may lead to new viral variants. IS therapy reduces antibody responses following coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination; however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and nonneutralizing antibody functions in addition to CD4 and CD8 T-cell interferon-γ responses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the standard COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals., Individuals on immunosuppression for various indications have impaired neutralizing, binding, and nonneutralizing antibody responses and reduced T-cell activity in response to COVID-19 mRNA vaccination compared to immunocompetent controls. This suggests that standard vaccination may not result in protective immunity in this population.

Hyperfunctioning parathyroid lesions require surgical resection.This study was a retrospective analysis. A total of 68 patients who were diagnosed as parathyroid lesions byTheThe degree of

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Post-pyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that post-pyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques.ImportanceSARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here we report that oral administration of live SARS-CoV-2 in non-human primates may offer prophylactic benefits, but that formulation and route of administration will require further optimization.

To detect sparse small objects in high resolution images at a low cost is significantly more challenging than regular detection tasks. Compared to the overall detection accuracy, the recall rate is much less affected when using properly downsampled images for detection. Based on this fact, we propose a clustering-based coarse-to-fine object detection framework to enhance the object detection of sparse small objects. The first stage is coarse detection on a downsampled image to obtain image chips based on a clustering-baed region generation method. After that, the associated high resolution image clips are sent to a second-stage detector for fine detection. This approach reduces the number of chips for final object detection compared to regular methods, which divide the image into small tiles of the same size, and makes the best use of information in high-resolution images to increase detection accuracy. Experimental results show that our proposed approach achieves promising performance compared with other state-of-the-art detectors.

BackgroundA cluster of over a thousand infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. Immune responses in breakthrough infections with the SARS-CoV-2 delta variant remain to be defined.MethodsHumoral and cellular immune responses were assessed in 35 vaccinated individuals who were tested for SARS-CoV-2 in the Massachusetts Department of Public Health outbreak investigation.ResultsVaccinated individuals who tested positive for SARS-CoV-2 demonstrated substantially higher antibody responses than vaccinated individuals who tested negative for SARS-CoV-2, including 28-fold higher binding antibody titers and 34-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed 4.4-fold higher Spike-specific CD8+ T cell responses against the SARS-CoV-2 delta variant than vaccinated individuals who tested negative.ConclusionsFully vaccinated individuals developed robust anamnestic antibody and T cell responses following infection with the SARS-CoV-2 delta variant. These data suggest important immunologic benefits of vaccination in the context of breakthrough infections.

PSMA3, a member of the proteasome subunit, has been shown to play a major player in protein degradation. Reportedly, PSMA3 functions as a negative regulator in various cancers, including colon, pancreatic and gastric cancers. However, the contribution of PSMA3 to the progression of esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remain unclear. Therefore, in this study, we investigated whether PSMA3 is involved in ESCC progression and the potential underlying mechanism. The results revealed that PSMA3 was highly expressed in the ESCC tumor tissues and functioned as a negative indicator according to the data from The Cancer Genome Atlas (TCGA)/ Gene Expression Omnibus (GEO) datasets and clinical patients' samples. Pathway enrichment analysis showed that PSMA3 was closely correlated with ESCC cancer stemness and the inflammatory response; however, this correlation was absent after knockdown of PSMA3 in vitro. We further demonstrated that PSMA3 suppressed CD8+ T cells infiltration depending on the C-C motif chemokine ligand 3 (CCL3)/C-C motif chemokine receptor 5 (CCR5) axis. Collectively, these results demonstrate the role of PSMA3 in ESCC cancer stemness and the negative regulation of CD8 T cells infiltration mediated by PSMA3. The results of this study may provide a potential target for the immuno-oncology effect of PSMA3 in ESCC therapy. This article is protected by copyright. All rights reserved.

Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.

Cadmium (Cd) is a widely prevalent environmental pollutant that accumulates in the liver and induces liver injury. The mechanism of Cd-induced liver injury remains elusive. Our study aimed to clarify the mechanism by which changes in the gut microbiota contribute to Cd-induced liver injury. Here, a murine model of liver injury induced by chronic Cd exposure was used. Liver injury was assessed by biochemistry and histopathology. Expression profiles of genes involved in bile acid (BA) homeostasis, inflammation and injury were assessed via Realtime-PCR and Western-blot. 16S rRNA gene sequencing and mass spectrometry-based metabolomics were used to investigate changes in the gut microbiota and its metabolites in the regulation of Cd-induced liver injury. Here, we showed that Cd exposure induced hepatic ductular proliferation, hepatocellular damage and inflammatory infiltration in mice. Cd exposure induced gut microbiota dysbiosis and reduced the fecal bile salt hydrolase activity leading to an increase of tauro-β-muricholic acid levels in the intestine. Cd exposure decreased intestine FXR/FGF-15 signaling and promoted hepatic BA synthesis. Furthermore, the mice receiving fecal microbiota transplantation from Cd-treated mice showed reduced intestinal FXR/FGF-15 signaling, increased hepatic BA synthesis, and liver injury. However, the depletion of the commensal microbiota by antibiotics failed to change these indices in Cd-treated mice. Finally, the administration of the intestine-restricted FXR agonist fexaramine attenuated the liver injury, improved the intestinal barrier, and decreased hepatic BA synthesis in the Cd-treated mice. Our study identified a new mechanism of Cd-induced liver injury. Cd-induced gut microbiota dysbiosis, decreased feces BSH activity, and increased intestinal T-βMCA levels led to an inhibition of intestinal FXR/FGF-15 signaling and an increase in hepatic BA synthesis, ultimately facilitating the development of hepatic ductular proliferation, inflammation, and injury in mice. This study expands our understanding of the health hazards caused by environmental Cd pollution.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that result in increased transmissibility and partial evasion of neutralizing antibodies have recently emerged. Whether natural immunity induced by the original SARS-CoV-2 WA1/2020 strain protects against rechallenge with these SARS-CoV-2 variants remains a critical unresolved question. In this study, we show that natural immunity induced by the WA1/2020 strain leads to partial but incomplete protection against the SARS-CoV-2 variants B.1.1.7 (alpha) and B.1.351 (beta) in rhesus macaques. We challenged rhesus macaques with B.1.1.7 and B.1.351 and showed that infection with these variants resulted in high viral replication in the upper and lower respiratory tract. We then infected rhesus macaques with the WA1/2020 strain and rechallenged them on day 35 with the WA1/2020, B.1.1.7, or B.1.351 variants. Natural immunity to WA1/2020 led to robust protection against rechallenge with WA1/2020 but only partial protection against rechallenge with B.1.351. An intermediate degree of protection was observed in rhesus macaques against rechallenge with B.1.1.7. These data demonstrate partial but incomplete protective efficacy of natural immunity induced by WA1/2020 against SARS-CoV-2 variants of concern. Our findings have important implications for both vaccination and public health strategies in the context of emerging SARS-CoV-2 variants of concern.

The a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a novel SARS-Cov-2-specific artificial antigen presenting cell (aAPC), coupled with a rapid expansion protocol (REP) as practiced in tumor infiltrating lymphocytes (TIL) therapy, we generate an immune catalytic quantity of Virus Induced Lymphocytes (VIL). Using T cell receptor (TCR)-specific aAPCs carrying co-stimulatory molecules and major histocompatibility complex (MHC) class-I immunodominant SARS-CoV-2 peptide-pentamer complexes, we expand virus-specific VIL derived from peripheral blood mononuclear cells (PBMC) of convalescent COVID-19 patients up to 1000-fold. This is achieved in a clinically relevant 7-day vein-to-vein time-course as a potential adoptive cell therapy (ACT) for COVID-19. We also evaluate this approach for other viral pathogens using Cytomegalovirus (CMV)-specific VIL from donors as a control. Rapidly expanded VIL are enriched in virus antigen-specificity and show an activated, polyfunctional cytokine profile and T effector memory phenotype which may contribute to a robust immune response. Virus-specific T cells can also be delivered allogeneically via MHC-typing and patient human leukocyte antigen (HLA)-matching to provide pragmatic treatment in a large-scale therapeutic setting. These data suggest that VIL may represent a novel therapeutic option that warrants further clinical investigation in the armamentarium against COVID-19 and other possible future pandemics.

Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine for COVID-19 have recently been reported1–3. We describe here the 8-month durability of humoral and cellular immune responses in 20 individuals who received one or two doses of 5×1010 vp or 1011 vp Ad26.COV2.S and in 5 participants who received placebo2. We evaluated antibody and T cell responses on day 239, which was 8 months after the single-shot vaccine regimen (N=10) or 6 months after the two-shot vaccine regimen (N=10), although the present study was not powered to compare these regimens3. We also report neutralizing antibody responses against the parental SARS-CoV-2 WA1/2020 strain as well as against the SARS-CoV-2 variants D614G, B.1.1.7 (alpha), B.1.617.1 (kappa), B.1.617.2 (delta), P.1 (gamma), B.1.429 (epsilon), and B.1.351 (beta).

Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine for COVID-19 have recently been reported1-3. We describe here the 8-month durability of humoral and cellular immune responses in 20 individuals who received one or two doses of 5×1010 vp or 1011 vp Ad26.COV2.S and in 5 participants who received placebo2. We evaluated antibody and T cell responses on day 239, which was 8 months after the single-shot vaccine regimen (N=10) or 6 months after the two-shot vaccine regimen (N=10), although the present study was not powered to compare these regimens3. We also report neutralizing antibody responses against the parental SARS-CoV-2 WA1/2020 strain as well as against the SARS-CoV-2 variants D614G, B.1.1.7 (alpha), B.1.617.1 (kappa), B.1.617.2 (delta), P.1 (gamma), B.1.429 (epsilon), and B.1.351 (beta).

Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting.To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2.In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022.Participants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2.Humoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8+ and CD4+ T-cell responses were evaluated by intracellular cytokine staining assays.Among 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16.Heterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.

Benzene is a pollutant that widely exists in the environment and in occupational workplaces. Its exposure is closely associated with hematological disorders and even leukemia, which poses a significant threat to public health. Thus, the underlying mechanisms should be explored. In the current study, it was investigated whether ferroptosis plays a role in benzene hematopoietic toxicity and related mechanisms. Mice were subcutaneously injected with benzene at 150 mg/kg b.w. to establish a hematotoxicity model. Four weeks later, the mice exposed to benzene exhibited a decrease in white blood cells, red blood cells, and hemoglobin level, as well as reduction in frequency of hematopoietic stem and progenitor cells (HS/PCs) and the colony forming abilities of CFU-G, CFU-M, CFU-GM, and CFU-GEMM. Simultaneously, apart from ferroptosis features in the mitochondrial morphology, decreased ATP and mitochondrial membrane potential, alterations in biochemical indices and gene expression were also observed, such as increased intracellular iron and lipid peroxidation, glutathione (GSH) depletion, and reduced glutathione peroxidase (GSH-Px) level, and upregulated PTGS2. Meanwhile, markedly altered expression of SLC7A11, GPX4, GCLC, NOX1, TFRC, FTH1, and FTL hinted that redox imbalance and dysfunction of iron uptake and storage are vital to induce ferroptosis. Additionally, decreased cytoplasmic NRF2 and increased nuclear NRF2 were also found, suggesting the activation of the NRF2 pathway. More importantly, inhibition of ferroptosis with ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially relieved the hematopoietic injuries. Our findings imply that dysregulation in the system Xc

Importance Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited. Objective To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern. Design, setting, and participants An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection. Main outcomes and measures SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine-staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants. Results This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants. Conclusion and relevance In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.

Obesity, a global public health issue, is characterized by excessive adiposity and is strongly related to some chronic diseases including cardiovascular diseases and diabetes. Extra energy intake-induced adipogenesis involves various transcription factors and long noncoding RNAs (lncRNAs) that control lipogenic mRNA expression. Currently, lncRNAs draw much attention for their contribution to adipogenesis and adipose tissue function. Increasing evidence also manifests the pivotal role of lncRNAs in modulating white, brown, and beige adipose tissue development and affecting the progression of the diseases induced by adipose dysfunction. The aim of this review is to summarize the roles of lncRNAs in adipose tissue development and obesity-caused diseases to provide novel drug targets for the treatment of obesity and metabolic diseases.

Aim Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Silibinin is a flavonoid compound which has medicinal value. Previous studies revealed that silibinin exhibited an anti-fibrotic effect. However, whether silibinin could attenuate high-fat diet (HFD)-induced renal fibrosis remains unclear. Therefore, this study aimed to explore the molecular mechanism by which silibinin regulated renal fibrosis induced by HFD. Methods In the present study, human renal glomerular endothelial cells (HRGECs) were treated with various concentrations of silibinin. Then, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. In addition, HRGECs were exposed to 100 nM TGF-β1 for mimicking in vitro renal fibrosis. The expressions of collagen I, fibronectin, and α-SMA were detected by reverse transcription-quantitative polymerase chain reaction and Western blot. Protein levels of p-IκB and p-p65 were examined by Western blot; meanwhile, level of NF-κB was measured by immunofluorescence staining. Furthermore, HFD-induced mouse model of renal fibrosis was established. The mouse body weight, fasting glucose, kidney weight/body weight, microalbuminuria, kidney histopathology, and fibrotic area were measured to assess the severity of renal fibrosis. Results Low concentration of silibinin (≤50 μM) had no cytotoxicity, while high concentration of silibinin (≥75 μM) exhibited significant cytotoxicity. Additionally, TGF-β1 increased the expressions of collagen I, fibronectin, α-SMA, p-IκB, and p-p65 and decreased the level NF-κB, while these effects were notably reversed by 50 μM silibinin. Moreover, both 50 and 100 mg/kg silibinin greatly decreased HFD-induced the upregulation of kidney weight/body weight, microalbuminuria, and fibrotic area. 100 mg/kg silibinin markedly reduced collagen I, fibronectin, and p-p65 expressions in mice renal tissues. Conclusion Silibinin was able to attenuate renal fibrosis in vitro and in vivo via inhibition of NF-κB. These data suggested that silibinin may serve as a potential agent to alleviate the renal fibrosis of DN.

Fluorescence resonance energy transfer between cerium ion(III) and levofloxacin is studied in a micellar solution of cetyltrimethyl ammonium bromide. A non-fluorescent 1:2 complex was formed betwee...

Potato virus Y (PVY) is a common pathogen affecting agricultural production worldwide and is mainly transmitted by Myzus persicae in a non-persistent manner. Insect-borne plant viruses can modify the abundance, performance, and behavior of their vectors by altering host plant features; however, most studies have overlooked the fact that the dynamic progression of virus infection in plants can have variable effects on their vectors. We addressed this point in the present study by dividing the PVY infection process in tobacco into three stages (early state, steady state and late state); delineated by viral copy number. We then compared the differential effects of PVY-infected tobacco (Nicotiana tabacum) plants on the host selection and feeding behavior of M. persicae. We used Y-shaped olfactory apparatus and electrical penetration graph (EPG) methods to evaluate host selection and feeding behavior, respectively. Interestingly, we found that PVY-infected plants at the steady state attracted more aphids than healthy plants, whereas no differences were observed for those at the early and late states. In terms of feeding behavior, intracellular punctures (closely related to PVY acquisition and transmission) were more abundant on PVY-infected tobacco plants at the early and steady states of infection than in uninfected plants. These results indicate that PVY-infected host plants can alter the host selection and feeding behavior of aphids in a stage-dependent manner, which is an important consideration when studying the interactions among host plants, viruses, and insect vectors. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.

A two-component material (Fe3O4@CaSiO3) with an Fe3O4 magnetite core and layered porous CaSiO3 shell from calcium nitrate and sodium silicate was synthesized by precipitation. The structure, morphology, magnetic properties, and composition of the Fe3O4@CaSiO3 composite were characterized in detail, and its adsorption performance, adsorption kinetics, and recyclability for Cu2+, Ni2+, and Cr3+ adsorption were studied. The Fe3O4@CaSiO3 composite has a 2D core–layer architecture with a cotton-like morphology, specific surface area of 41.56 m2/g, pore size of 16 nm, and pore volume of 0.25 cm3/g. The measured magnetization saturation values of the magnetic composite were 57.1 emu/g. Data of the adsorption of Cu2+, Ni2+, and Cr3+ by Fe3O4@CaSiO3 fitted the Redlich–Peterson and pseudo-second-order models well, and all adsorption processes reached equilibrium within 150 min. The maximum adsorption capacities of Fe3O4@CaSiO3 toward Cu2+, Ni2+, and Cr3+ were 427.10, 391.59, and 371.39 mg/g at an initial concentration of 225 mg/L and a temperature of 293 K according to the fitted curve with the Redlich–Peterson model, respectively. All adsorption were spontaneous endothermic processes featuring an entropy increase, including physisorption, chemisorption, and ion exchange; among these process, chemisorption was the primary mechanism. Fe3O4@CaSiO3 exhibited excellent adsorption, regeneration, and magnetic separation performance, thereby demonstrating its potential applicability to removing heavy metal ions.

A novel ion-imprinted blend membrane was fabricated to separate selectively platinum(IV) from aqueous media. An amphiphilic copolymer poly(methyl methacrylate)-b-poly(4-vinylpyridine) (PMMA-b-P4VP) was firstly synthesized via the reversible addition fragmentation chain transfer polymerization, and characterized by 1H NMR, FT-IR and GPC. Subsequently, poly(vinylidene fluoride) (PVDF) blend membranes were prepared using PMMA-b-P4VP as a blending additive. Effects of the following factors on performance of blend membranes were systematically examined: P4VP content of PMMA-b-P4VP, solvent type, and PMMA-b-P4VP/PVDF ratio. Further, platinum(IV) ion-imprinted membrane (Pt(IV)-IIM) was fabricated by blending polymer-Pt(IV) complexes with PVDF. SEM, FTIR-ATR, contact angle, water flux and adsorption capacity were employed to characterize all membranes. Results indicated that the membrane, which was prepared using the copolymer with high P4VP content (polymerization time 10 h) as a functional polymer, N,N-dimethylacetamide as a solvent and PMMA-b-P4VP/PVDF ratio of 30 wt%, exhibited an intriguing morphology and much higher performance. Pt(IV)-IIM showed higher adsorption and selectivity for Pt(IV) (selectivity coefficients of 27.66 ± 1.38 and 77.16 ± 3.86 for Pt(IV)/Cu(II) and Pt(IV)/Ni(II), respectively) compared with a non-imprinted membrane. During membrane filtration, Pt(IV)-IIM was effective and selective for separation of Pt(IV) in the presence of Cu(II) and Ni(II) ions. Also, Pt(IV)-IIM was chemical stable, and had a good regeneration performance.

The adsorption characteristic and mechanism of poly(N1,N1,N3,N3-tetraallylpropane-1,3-diaminium chloride) (PTAPDAC) toward Cr(VI) ions were systematically investigated. Results showed that the remo...

The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian-human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.

Importance Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. Objective To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. Design, Setting, and Participants Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. Interventions Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010viral particles or 1 × 1011viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). Main Outcomes and Measures Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. Results Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. Conclusion and Relevance In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine. Trial Registration ClinicalTrials.gov Identifier:NCT04436276

We previously reported that a single immunization with an adenovirus serotype 26 (Ad26) vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. To evaluate reduced doses of Ad26.COV2.S, 30 rhesus macaques were immunized once with 1x1011, 5x1010, 1.125x1010, or 2x109 vp Ad26.COV2.S or sham and were challenged with SARS-CoV-2. Vaccine doses as low as 2x109 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125x1010 vp were required for protection in nasal swabs. Activated memory B cells and binding or neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show enhancement of disease. These data demonstrate that a single immunization with relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques, although a higher vaccine dose may be required for protection in the upper respiratory tract., Evaluation of a reduced dosage of the single-shot Ad26.COV2.S reveals protection across different tissues protects against SARS-CoV-2 challenge and enhancement of disease. A higher dosage may be needed for protection in the upper respiratory tract.