Based on atmosphere reanalysis data from ERA5 and sea surface temperature (SST) from Hadley Center, this study investigates the triggering effect of the subtropical Indian Ocean Dipole (SIOD) on the subsequent tropical Indian Ocean Dipole (IOD), as well as its interdecadal change, from 1960 to 2024. Results show that the correlations between the SIOD and IOD are not significant from 1960 to the late 1980s (WEAK period), whereas, stable positive correlations appear between them from the late 1980s onward (STRONG period). During the STRONG period, the positive SST anomalies (SSTA) in the southwestern Indian Ocean as well as the overlying anomalous anticyclonic circulation (AC), associated with the positive SIOD, are sustained and shift eastward under the positive wind-evaporation-SST (WES) feedback. This SSTA drives a vertical motion of the above atmosphere through diabatic heating, subsequently promoting the development of the low-level AC and its equatorward expansion by exciting Rossby wave trains and local meridional circulation. Ultimately, the development of IOD is triggered and enhanced through air–sea coupling processes, including the Bjerknes feedback, Walker circulation, and oceanic Rossby waves. In contrast, during the WEAK period, the responses of the aforementioned physical processes are weak, preventing an effective influence of the SIOD on the IOD. Further analysis indicates that the variation of Southern Annular Mode (SAM), particularly its intensity, plays a significant role in the interdecadal shift of the SIOD-to-IOD relationship. This paper provides new insights for understanding cross-latitude air–sea interactions and improving seasonal IOD prediction.

Respiratory syncytial virus (RSV) prefusion F (preF) vaccines have transformed adult prophylaxis, yet unmet needs in antigen stability, pediatric safety, and mucosal protection persist. Here, we develop an integrated structure-guided RSV vaccine design platform that couples allosteric stabilization, epitope-focused immunogen engineering, and route-specific mRNA delivery for systemic and mucosal immune activations. By mapping prefusion F "breathing" motions and applying a ThermoNet- and Rosetta-guided screening funnel, we identified R296, a stabilized prefusion F immunogen that reinforces the α1-α5 hinge and interprotomer interfaces while preserving key neutralizing epitopes. Cryo-EM confirmed that R296 retains a native-like prefusion architecture. And mRNA-LNP vaccination elicited potent, durable, and broadly protective neutralizing responses in mice, rats, and cotton rats, with clearance of detectable infectious virus and no evidence of Th2-skewed enhanced respiratory disease. To address pediatric safety, we designed a stalkless nanoparticle immunogen, Head38-50AB-3, which enriches high-potency apical epitopes while excluding stalk regions associated with low-potency or non-protective responses, conferring protection without VAERD-like pathology. Finally, we engineered an intranasal-delivered LNP that enables intranasal R296 mRNA delivery, inducing systemic neutralization together with robust nasal and bronchoalveolar secretory IgA (sIgA). R296 has now advanced to Phase 1 clinical trials. These results establish a modular framework for next-generation RSV vaccines.

Based on observational and reanalysis datasets, this study examines the relationship between the tropical Indian Ocean Dipole (IOD) that matures in boreal autumn and the subsequent Subtropical Indian Ocean Dipole (SIOD) that occurs in the following boreal winter, as well as its interdecadal variability over 1960-2024. Results suggest that a significant correlation between IOD and SIOD only exists in 1979-2005. During this strong correlation period, an intense IOD can trigger a persistent meridional circulation and mid-latitude Rossby wave train, maintaining an anomalous cyclone-anticyclone pair (CACP) over the subtropical Indian Ocean, with the cyclone in the west and the anticyclone in the east, ultimately leading to the development of SIOD via local air-sea coupling. In other periods, this relationship weakens and the described coupling pathway fails to establish. A key factor enabling this efficient cross-seasonal linkage is the presence of sustained oceanic memory. Specifically, the sea surface temperature and subsurface heat anomalies associated with the IOD persist from boreal autumn into winter, providing a thermal precondition that interacts with the atmospheric circulation to eventually develop the SIOD. Further analysis indicates that this interdecadal variation is modulated by the Interdecadal Pacific Oscillation (IPO). Specifically, the positive phase of IPO strengthens the Indo-Pacific Walker circulation anomaly, reinforces the tropical-subtropical meridional pathway, and thereby enhances the IOD's triggering effect on SIOD. In contrast, the negative IPO phase suppresses this pathway. This study offers new mechanistic insights that advance our understanding of cross-seasonal interactions in the Indian Ocean and contribute to improved climate predictions. Furthermore, it clarifies the importance of accounting for non-stationarity in the climatic background for seasonal forecasting.

Introduction Using three moorings deployed at 122.7 degrees E, 123 degrees E, and 123.3 degrees E along 18 degrees N from January 2018 to May 2020, this study investigates the seasonal variability of the Kuroshio Current (KC).Methods Sensitive experiments were conducted with the Regional Ocean Modeling System (ROMS).Results In 2019, the KC exhibited a typical seasonal cycle, being relatively strong during spring, summer, and winter, with the weakest flow occurring in autumn. In contrast, the KC displayed an atypical seasonal cycle in 2018, characterized by two distinct intraseasonal intensification events in late September and early November. The ROMS experiments revealed that local winds within the region (120 degrees E-125 degrees E, 15 degrees N-20 degrees N) were the primary driver of this atypical cycle. During the two key periods, persistent negative wind stress curl anomalies east of the mooring stations induced integrated positive sea surface height anomalies and corresponding northward meridional velocity anomalies via geostrophic balance.Discussion In 2019, the wind stress curl anomaly phases reversed compared to 2018, leading to the absence of the two peaks observed in the previous year.

We used the ocean reanalysis dataset SODA2.2.4 to investigate the relationship between the interior branch of subtropical-tropical cells (STCs) in the Pacific Ocean and El Niño-Southern Oscillation (ENSO) over interdecadal timescales between 1930 and 2010, as well as the possible mechanisms involved. Interior transport within the upper pycnocline layers of STCs (InSTC) along 9°S (InSTC9s) shows a significant correlation of −0.54 with ENSO over the study period. However, there is an interdecadal shift in the relationship between InSTC along 9°N (InSTC9n) and ENSO. The correlation coefficient between InSTC9n and ENSO is not statistically significant between 1930 and 1965 (PD1), but is as high as 0.68 (significant at the 95

Dear Editor, African swine fever(ASF),caused by the African swine fever virus(ASFV),is a highly contagious swine disease with nearly 100％mortality in severe hemorrhagic cases(Dixon et al.,2019).As the swine industry is vital to agriculture,recent ASF outbreaks have raised concerns about global economic stability and food security(Wang et al.,2019).Controlling ASF is challenging due to the virus's stability,ability to evade immunity,and lack of effective vaccines or treatments.

Several human papillomavirus (HPV) L1-based virus-like particle (VLP) vaccines are in development to meet future global vaccination needs. Type-specific monoclonal antibodies with good reactivity to all types of vaccines are urgently needed to evaluate vaccine potency. In this study, binding activity, neutralizing activity, conformational sensitivity, immunodominance in human serum, and versatility were compared among antibodies. A broad-spectrum binding antibody (C4-F5-127) was selected as the capture antibody; four type-specific neutralizing antibodies (6-F5-77, 11-F5-187, 16-F5-196, and 18-F5-203) were selected as detection antibodies for HPV6, 11, 16, and 18, respectively. These antibodies formed a standardized and universal in vitro relative potency (IVRP) assay kit. High-resolution cryo-electron microscopy (cryo-EM) structures of HPV6-6-F5-77, HPV11-11-F5-187, HPV16-16-F5-196 and HPV18-18-F5-203 complexes define the location and nature of epitopes, revealing serotype specific binding modes and neutralization mechanisms. The IVRP results were correlated with potency data from mouse models, offering an efficient alternative to in vivo potency experiments.

Decades of human papillomavirus (HPV) L1-based virus-like particle (VLP) vaccines, produced using diverse expression systems and production processes, are in development to meet future global vaccination needs. Type-specific monoclonal antibodies with good reactivity to all types of vaccines are urgently needed to evaluate vaccine efficacy. In this study, binding activity, neutralizing activity, conformational sensitivity, immunodominance in human serum, and versatility were compared among antibodies. A broad-spectrum binding antibody (F5-127) was selected as the capture antibody; four type-specific neutralizing antibodies (F5-77, F5-187, F5-196, and F5-203) were selected as detection antibodies for HPV6, 11, 16, and 18, respectively. These antibodies formed a standardized and universal in vitro relative potency (IVRP) assay kit useful for all quadrivalent HPV vaccines. High-resolution cryo-electron microscopy (cryo-EM) structures of HPV6-F5-77, HPV11-F5-187, HPV16-F5-196 and HPV18-F5-203 complexes define the location and nature of epitopes, revealing serotype specific binding modes and neutralization mechanisms. These four antibodies target regions which exhibit structural plasticity within the L1 pentamer, rather than quaternary sites constructed by particle formation, conferring conformational sensitivity and reactive universality, pre-requisites as IVRP candidate antibodies. The IVRP results were correlated with efficacy data from mouse models, demonstrating the kit’s sensitivity in detecting the degree of heat-accelerated destruction. Therefore, the IVRP method established in this study offers an efficient alternative to in vivo efficacy experiments for future vaccines.

Spike-protein-based pseudotyped viruses were used to evaluate vaccines during the COVID-19 pandemic. However, they cannot be used to evaluate the envelope (E), membrane (M), and nucleocapsid (N) proteins. The first generation of virus-like particle (VLP) pseudotyped viruses contains these four structural proteins, but their titers for wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relatively low, even lower for the omicron variant, rendering them unsuitable for neutralizing antibody detection. By optimizing the spike glycoprotein signal peptide, substituting the complexed M and E proteins with SARS-COV-1, optimizing the N protein with specific mutations (P199L, S202R, and R203M), and truncating the packaging signal, PS9, we increased the titer of the wild-type VLP pseudotyped virus over 100-fold, and successfully packaged the omicron VLP pseudotyped virus. The SARS-CoV-2 VLP pseudotyped viruses maintained stable titers, even through 10 freeze-thaw cycles. The key neutralization assay parameters were optimized, including cell type, cell number, and viral inoculum. The assay demonstrated minimal variation in both intra- and interassay results, at 11.5% and 11.1%, respectively. The correlation between the VLP pseudotyped virus and the authentic virus was strong (r = 0.9). Suitable for high-throughput detection of various mutant strains in clinical serum. In summary, we have developed a reliable neutralization assay for SARS-CoV-2 based on VLP pseudotyped virus. Through the optimization of the structural proteins of coronavirus virus-like particle (VLP) pseudotyped virus, we successfully constructed high titer the VLP pseudotyped virus variant. We optimized the conditions for neutralizing antibodies and validated the methodology. We have established a detection method for neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VLP pseudotyped virus, which shows good consistency with authentic viruses and suitable for detecting various variants. image

In the Kuroshio Current (KC) source area, intraseasonal variation (ISV) plays a significant role in dynamic oceanic processes. This study used data collected from three moorings (122.7°E, 123°E, 123.3°E) along 18°N from January 2018 to May 2020 to investigate the ISVs of meridional velocities. Notably, our findings reveal that the ISV above 200 m has a period of approximately 56 days and its intensity exhibits a gradual increase toward the west. For the 500–800 m depth interval, the ISV period is 73 days at 122.7°E/18°N and 60 days at 123.3°E/18°N. This discrepancy indicates that the ISVs have different vertical structures and frequencies at 122.7°E and 123.3°E along 18°N. In particular, at 122.7°E/18°N, the distinctiveness of two different periods of ISVs in surface and subsurface layers was more pronounced in 2018 than in 2019. The analyses of eddy kinetic energy distribution and eddy tracking indicate a connection between ISV in stratification and locally generated mesoscale eddies in the KC source area. Specifically, the stronger eddy activity in 2018, in contrast with that in 2019, correlates with a more pronounced ISV. Energy analysis demonstrates a distinct positivity in the baroclinic conversion rate (BC) in the surface layer (upper 200 m) of the KC source region, surpassing the absolute value of the barotropic conversion rate (BT). This finding indicates a notable shift of energy from eddy available potential energy to eddy kinetic energy, strengthening the high-frequency ISV signals in this area. In the subsurface layer, a strong negative BT is observed west of 122.8°E, with its absolute value exceeding the BC. This finding indicates that the energy is converted from eddy kinetic energy into mean kinetic energy, resulting in the appearance of the Luzon Undercurrent (LUC) at mooring station 122.7°E/18°N, characterized by a low frequency of ISV. Contrastingly, a positive BT plays a dominant role at 123.3°E/18°N, leading to the disappearance of the LUC amid an apparent presence of high-frequency ISV.

Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-refractory and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines.

Intraseasonal variability (ISV) in the meridional velocity of multi-layer currents in the Philippines Sea was investigated using near full-depth mooring observations deployed at 130 degrees E, 11 degrees N from September 2015 to October 2019 and the reanalysis data from 2015 to 2019. Prominent bimodal ISVs structures were detected in the power spectra of the meridional velocities at 45- and 62-days, occurring from the surface through to the bottom. Further analysis suggested that the identified ISV of 62-days in the upper 1,500 m was controlled by large-scale oceanic Rossby waves with a zonal wavelength of 687 km. The full-depth 45-days fluctuation is limited by the entire zonal width of the Philippines Basin, which is approximately 900 km. The 45-days variability modulated by the barotropic Rossby normal mode triggered by resonant wind forcing in the key region of 126 degrees-140 degrees E and 5 degrees-13 degrees N. Whereas the deep-layer 62-days fluctuation is limited by the basin width near the bottom (5,700 m), which is approximately 640 km. In addition, two super-intense ISV events occurred in the upper layers following the 2015/16 and 2018/19 El Ni & ntilde;o events, which generally lagged the Ni & ntilde;o 3.4 index by six/seven months. This study reveals the upper-layer ocean ISVs response in the western Pacific following El Ni & ntilde;o events and triggering of the deep-layer ocean ISVs by the actual basin scale. Our findings provide a better understanding of the variations in full-depth currents in the western Pacific Ocean. Compared to the upper ocean variability, which is well-known to oceanographers, the variability of the intermediate-deep ocean is mysterious, because it is largely limited by the paucity of in situ observations in the deep ocean. The 4-year continuous direct current measurements used in this study are invaluable for studying the intraseasonal variability (ISV) of meridional velocity in the Philippine Sea. Near full-depth measurements revealed a bimodal ISV structure with 45-, and 62-days in the power spectrum of the meridional velocity. Further analysis demonstrated that the 62-day ISV of the meridional velocity in the upper ocean was mainly controlled by the westward-propagation first-mode baroclinic Rossby wave, and deep-layer ISVs of the meridional velocity were modulated by barotropic Rossby normal mode that depended on the actual Philippine basin scale. In addition, the two super-intense ISV events observed in the upper-layer ocean in the western Pacific were strongly associated with El Ni & ntilde;o events. This study revealed a previously unclear variability in deep-layer currents triggered by the actual basin scale, which greatly enriched our understanding of full-depth circulation variation in the Philippine Sea. Bimodal intraseasonal variability (ISV) in the full-depth meridional velocity was observed in the Philippine Sea Upper-layer 62 days ISV was controlled by the first-mode baroclinic Rossby wave, and its intensity increased dramatically after El Ni & ntilde;o Full-depth 45 days and deep-layer 62 days ISVs were modulated by the barotropic Rossby normal mode and triggered by resonant wind forcing

Newcastle disease virus (NDV) belongs to Paramyxoviridae, which contains lethal human and animal pathogens. NDV RNA genome is replicated and transcribed by a multifunctional 250 kDa RNA-dependent RNA polymerase (L protein). To date, high-resolution structure of NDV L protein complexed with P protein remains to be elucidated, limiting our understanding of the molecular mechanisms of Paramyxoviridae replication/transcription. Here, we used cryo-EM and enzymatic assays to investigate the structure-function relationship of L-P complex. We found that C-terminal of CD-MTase-CTD module of the atomic-resolution L-P complex conformationally rearranges, and the priming/intrusion loops are likely in RNA elongation conformations different from previous structures. The P protein adopts a unique tetrameric organization and interacts with L protein. Our findings indicate that NDV L-P complex represents elongation state distinct from previous structures. Our work greatly advances the understanding of Paramyxoviridae RNA synthesis, revealing how initiation/elongation alternates, providing clues for identifying therapeutic targets against Paramyxoviridae.

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summary A sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations.

Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.

The spatial distribution and temporal variability of the Kuroshio Current (KC) was investigated with three moorings deployed at 122.7° E, 123° E, and 123.3° E along 18° N from January 2018 to the spring of 2020. It is shown that the core of the KC is located to the west of 122.7° E along 18° N. With the increase in longitude, the KC extended its vertical scale and attenuated its intensity gradually. The satellite data indicated that the KC was strongest in winter and spring, while it was weakest in autumn along 18° N. However, the seasonal cycle of the KC from mooring observations was atypical compared with that from the satellite data. The seasonal variation of the KC was not obvious in 2018, and a summer peak of KC occurred in 2019. The atypical seasonal variability of the KC was attributed to the strong intraseasonal signals generated by eddy activity. Eddies propagated from east and were enhanced to the west of 140° E, leading to the westward intensified intraseasonal signals. In addition, the intraseasonal signals varied interannually, that is why the variation of the KC in 2018 was quite different with that in 2019.

Echovirus 3 (E3), a serotype of human enterovirus B (HEV-B), causes severe diseases in infants. Here, we determined the structures of E3 with a monoclonal antibody (MAb) 6D10 by cryo-EM to comprehensively understand the specificities and the immunological characteristic of this serotype. The solved cryo-EM structures of the F-, A-, and E-particles of E3 bound with 6D10 revealed the structural features of the virus–antibody interface. Importantly, the structures of E-particles bound with 6D10 revealed for the first time the nature of the C-terminus of VP1 for HEV-Bs at the structural level. The highly immunogenic nature of this region in the E-particles provides new strategies for vaccine development for HEV-Bs.