Protective non-neutralizing SARS-CoV-2 monoclonal antibodies.

Recent studies show an important role for non-neutralizing anti-spike antibodies, including monoclonal antibodies (mAbs), in robustly protecting against SARS-CoV-2 infection. These mAbs use Fc-mediated functions such as complement activation, phagocytosis, and cellular cytotoxicity. There is an untapped potential for using non-neutralizing mAbs in durable antibody treatments; because of their available conserved epitopes, they may not be as sensitive to virus mutations as neutralizing mAbs. Here, we discuss evidence of non-neutralizing mAb-mediated protection against SARS-CoV-2 infection. We explore how non-neutralizing mAb Fc-mediated functions can be enhanced via novel antibody-engineering techniques. Important questions remain to be answered regarding the characteristics of protective non-neutralizing mAbs, including the models and assays used for study, the risks of ensuing detrimental inflammation, as well as the durability and mechanisms of protection.

On the Performance of a Horizontally Mounted ADCP in an Energetic Tidal Environment for Floating Tidal Turbine Applications.

Incident flow measurement is key in the tidal industry for conducting power performance assessments. This paper explores the use of a horizontally mounted Nortek Signature 500 Acoustic Doppler Current Profiler (ADCP) as a means for incident flow measurement onboard a utility-scale tidal turbine. This study shows that the measurement range of an ADCP mounted horizontally in highly dynamic tidal flow (up to 4 m/s) is less than the maximum range stated by the manufacturer. The ability for the horizontal ADCP to accurately resolve velocities in a multi-beam configuration is also analysed. Effects from both vertical shear and beam selection result in incident flow velocities that differ from a single horizontal beam recording. The maximum measurement range of the instrument is found to depend on current speed and on the proportion of data loss that is acceptable to the user. The ability of the ADCP to record data from the free-stream velocity two equivalent diameters upstream of the O2, as set out by IEC TS 62600-200, is considered. It is found that at this distance, there is 90% data loss. Accepting only 10% data loss across all flow speeds resulted in a maximum range of 31 m for a Nortek Signature 500 in this study. While some limitations of an ADCP deployed horizontally in highly energetic tidal flow are identified, the benefits of mounting the sensor close to the rotor facing horizontally into the incoming flow mean that valuable data are still produced for tidal turbine operators.

Macrophage N-glycan processing inhibits antibody-dependent cellular phagocytosis.

Factors regulating macrophage effector function represent potential targets to optimize the efficacy of antibody-mediated therapies. Macrophages are myeloid cells capable of engulfing and destroying diseased or damaged target cells. Antibodies binding to the target cell surface can engage macrophage Fc gamma receptors (FcγRs) to elicit antibody-dependent cellular phagocytosis (ADCP), a process that contributes to treatments mediated by anti-tumor antibodies. Conversely, macrophage ADCP of apoptotic T cells is also linked to tolerance in the tumor environment. Here we evaluated the role of asparagine(N)-linked glycans in the function of macrophages derived from primary human monocytes. Macrophages treated with kifunensine, an inhibitor of N-glycan processing, exhibited greater target binding and ADCP of antibody-coated target cells. Kifunensine treatment increased ADCP of both rituximab-coated Raji B cells and trastuzumab-coated SKBR3 cells. ADCP required FcγRs; inhibiting CD64 / FcγRI led to the greatest reduction, followed by CD32 / FcγRII and then CD16 / FcγRIII in most donors. Kifunensine treatment also increased the antibody-binding affinity of CD16. Differences in the abundance of phosphorylated immune receptors, including Siglec-9, CD32a, and LAIR-1 correlated with the increased ADCP. These results demonstrate that N-glycan processing regulates macrophage effector function.

Reduced neutralization and Fc effector function to Omicron subvariants in sera from SARS-CoV-1 survivors after two doses of CoronaVac plus one dose subunit vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross-clade pan-sarbecovirus neutralizing antibodies in survivors of the infection by SARS-CoV-1, the neutralization activity and Fc-mediated effector functions of these cross-reactive antibodies elicited in SARS-CoV-1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc-mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS-CoV-1 convalescents and healthy individuals. Potent cross-clade broadly neutralizing antibodies were observed in SARS-CoV-1 survivors who received a three-dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS-CoV-1 infection may exacerbate the impairment of neutralization activity and Fc-mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. METHODS: Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. RESULTS: All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. CONCLUSIONS: Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.

Functional Activities of O-Polysaccharide and Hemolysin Coregulated Protein 1 Specific Antibodies Isolated from Melioidosis Patients.

Melioidosis is a fatal tropical disease caused by the environmental Gram-negative bacterium, Burkholderia pseudomallei. This bacterium is intrinsically resistant to several antibiotics and treatment of melioidosis requires prolonged antibiotic administration. To date, there are no vaccines available for melioidosis. Previous studies have shown that humoral immunity is critical for surviving melioidosis and that O-polysaccharide (OPS) and hemolysin coregulated protein 1 (Hcp1) are important protective antigens in animal models of melioidosis. Our previous studies revealed that melioidosis patients had high levels of OPS- and Hcp1-specific antibodies and that IgG against OPS (IgG-OPS) and Hcp1 (IgG-Hcp1) were associated with patient survival. In this study, we characterized the potential function(s) of IgG-OPS and IgG-Hcp1 from melioidosis patients. IgG-OPS and IgG-Hcp1 were purified from pooled serum obtained from melioidosis patients using immuno-affinity chromatography. Antibody-dependent cellular phagocytosis assays were performed with pooled serum from melioidosis patients and compared with serum obtained from healthy controls. Serum from melioidosis patients significantly enhanced B. pseudomallei uptake into the human monocytic cell line THP-1 compared with pooled serum from healthy donors. Enhanced opsonization was observed with IgG-OPS and IgG-Hcp1 in a dose-dependent manner. Antibody-dependent complement deposition assays were performed with IgG-OPS and IgG-Hcp1 using flow cytometry and showed that there was enhanced C3b deposition on the surface of B. pseudomallei treated with IgG-OPS but to a lesser degree with IgG-Hcp1. This study provides insight into the function of IgG-OPS and IgG-Hcp1 in human melioidosis and supports that OPS and Hcp1 are potential vaccine antigens for immunization against melioidosis.

Efficacy and mechanism of the anti-CD38 monoclonal antibody Daratumumab against primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare, aggressive B cell non-Hodgkin's lymphoma of the body cavities with malignant effusions. The prognosis is poor, and no optimal treatment has been established. CD38 is a type II transmembrane glycoprotein known to overexpress in multiple myeloma (MM). Daratumumab (DARA), a human CD38-targeting monoclonal antibody (mAb), is approved for MM treatment. In this study, we found expression of CD38 on PEL cells and assessed the anti-PEL activity of DARA. We found that both KHYG-1 and N6 (CD16-transfected KHYG-1) NK cell lines showed direct killing activity against PEL cells with induction of CD107a, and NK-mediated cytotoxicity by N6NK (CD16+) cells increased with DARA treatment. We confirmed direct NK activity and antibody-dependent cell cytotoxicity (ADCC) by expanded NK cells, indicating that DARA has high ADCC activity. We elucidated the antibody-dependent cell phagocytosis (ADCP) by using human monocyte-derived macrophages (MDMs) and mouse peritoneal macrophages. DARA also showed potent complement-dependent cytolysis (CDC) toward PEL. DARA also induced PEL cell death in the presence of a cross-linking antibody. Moreover, treatment with DARA inhibited tumor growth in a PEL xenograft mouse model. These results provide preclinical evidence that Ab targeting of CD38 could be an effective therapeutic strategy for the treatment of PEL.

Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses.

Daily burden and clinical toxicities associated with antiretroviral therapy (ART) emphasize the need for alternative strategies to induce long-term human immunodeficiency virus (HIV) remission upon ART cessation. Broadly neutralizing antibodies (bNAbs) can both neutralize free virions and mediate effector functions against infected cells and therefore represent a leading immunotherapeutic approach. To increase potency and breadth, as well as to limit the development of resistant virus strains, it is likely that bNAbs will need to be administered in combination. It is therefore critical to identify bNAb combinations that can achieve robust polyfunctional antiviral activity against a high number of HIV strains. In this study, we systematically assessed the abilities of single bNAbs and triple bNAb combinations to mediate robust polyfunctional antiviral activity against a large panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies targeting the HIV envelope in nonhuman primate models. We demonstrate that most bNAbs are capable of mediating both neutralizing and nonneutralizing effector functions against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs is highly strain dependent. Moreover, we observe a strong correlation between the neutralization potencies and nonneutralizing effector functions of bNAbs against the transmitted/founder SHIV CH505. Finally, we identify several triple bNAb combinations comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs.IMPORTANCE Optimal bNAb immunotherapeutics will need to mediate multiple antiviral functions against a broad range of HIV strains. Our systematic assessment of triple bNAb combinations against SHIVs will identify bNAbs with synergistic, polyfunctional antiviral activity that will inform the selection of candidate bNAbs for optimal combination designs. The identified combinations can be validated in vivo in future passive immunization studies using the SHIV challenge model.

SailBuoy Ocean Currents: Low-Cost Upper-Layer Ocean Current Measurements.

This study introduces an alternative to the existing methods for measuring ocean currents based on a recently developed technology. The SailBuoy is an unmanned surface vehicle powered by wind and solar panels that can navigate autonomously to predefined waypoints and record velocity profiles using an integrated downward-looking acoustic Doppler current profiler (ADCP). Data collected on two validation campaigns show a satisfactory correlation between the SailBuoy current records and traditional observation techniques such as bottom-mounted and moored current profilers and moored single-point current meter. While the highest correlations were found in tidal signals, strong current, and calm weather conditions, low current speeds and varying high wave and wind conditions reduced correlation considerably. Filtering out some events with the high sea surface roughness associated with high wind and wave conditions may increase the SailBuoy ADCP listening quality and lead to better correlations. Not yet resolved is a systematic offset between the measurements obtained by the SailBuoy and the reference instruments of ±0.03 m/s. Possible reasons are discussed to be the differences between instruments (various products) as well as changes in background noise levels due to environmental conditions.

Comparison of Flows through a Tidal Inlet in Late Spring and after the Passage of an Atmospheric Cold Front in Winter Using Acoustic Doppler Profilers and Vessel-Based Observations.

This paper discusses the application of acoustic Doppler current profilers (ADCP) for the quantification of transport of water and the underlining physical mechanism. The transport of water through estuaries and tidal inlets is affected by tide, river flow, and wind. It is often assumed that wind effects in such systems are negligible unless under severe weather conditions. This study compares the ADCP-measured flows across a tidal inlet under weak wind conditions in late spring and those after the passage of an atmospheric cold front in winter. The Barataria Pass is a major inlet connecting Barataria Bay and northern Gulf of Mexico. The water exchange between the bay and coastal ocean is influenced by wind, especially in winter, because tide in the region is small (microtidal). The winter weather and late spring-summer weather are different. This difference results in different estuarine circulations. To examine this, two surveys were carried out with ship-mounted ADCPs-one in winter (19 December 2014) shortly after the passage of a cold front from the northwest, and the other in late spring (4 May 2015) with weak southeasterly winds. Distinctly different features of mean transport through the inlet were observed between the two surveys. The results from the first survey in winter showed that the total water transport was from the bay to the coastal ocean under northerly winds with intense outflows in shallow water, which is a typical signature of wind effects. The net flow was outward when the water level dropped. Data from the second survey in spring showed that the mid-channel water flew out of the bay (against the wind), whilst inflow appeared at both ends across the inlet, which was also a response to the weak wind stress and outward pressure gradient force set by the estuarine flow. The inflow at the eastern end (exceeding 0.1 m/s) is consistent with the idea that the coastal current resulted from the Mississippi River outflow enters the bay from the eastern end. The influence of tidal oscillations on water exchange appeared to be higher in the late spring data. The hydrographic observations in spring showed typical tidal straining features of an inverse estuary during the ebb-flood cycle, while salinity in the eastern shallow water generally varied with time, indicating the inflow of fresher water into the bay, confirming previous observations from summer 2008.

Functional Characterization of Largemouth Bass (Micropterus salmoides) Soluble FcγR Homolog in Response to Bacterial Infection.

Fc receptors (FcRs) are key players in antibody-dependent cellular phagocytosis (ADCP) with their specific recognition of the Fc portion of an immunoglobulin. Despite reports of FcγR-mediated phagocytosis in mammals, little is known about the effects of soluble FcγRs on the immune response. In this study, FcγRIα was cloned from the largemouth bass (Micropterus salmoides) (MsFcγRIα). Without a transmembrane segment or a cytoplasmic tail, MsFcγRIα was identified as a soluble form protein and widely distributed in the spleen, head kidney, and intestine. The native MsFcγRIα was detected in the serum of Nocardia seriolae-infected largemouth bass and the supernatants of transfected HEK293 cells. Additionally, it was verified that the transfected cells' surface secreted MsFcRIα could bind to largemouth bass IgM. Moreover, the expression changes of MsFcγRIα, Syk, and Lyn indicated that MsFcγRIα was engaged in the acute phase response to bacteria, and the FcγR-mediated phagocytosis pathway was activated by Nocardia seriolae stimulation. Furthermore, recombinant MsFcγRIα could enhance both reactive oxygen species (ROS) and phagocytosis to Nocardia seriolae of leukocytes, presumably through the interaction of MsFcγRIα with a complement receptor. In conclusion, these findings provided a better understanding of the function of soluble FcγRs in the immune response and further shed light on the mechanism of phagocytosis in teleosts.

Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques.

The RV144 vaccine trial revealed a correlation between reduced risk of HIV infection and the level of nonneutralizing-antibody (Ab) responses targeting specific epitopes in the second variable domain (V2) of the HIV gp120 envelope (Env) protein, suggesting this region as a target for vaccine development. To favor induction of V2-specific Abs, we developed a vaccine regimen that included priming with DNA expressing an HIV V1V2 trimeric scaffold immunogen followed by booster immunizations with a combination of DNA and protein in rhesus macaques. Priming vaccination with DNA expressing the HIV recombinant subtype CRF01_AE V1V2 scaffold induced higher and broader V2-specific Ab responses than vaccination with DNA expressing CRF01_AE gp145 Env. Abs recognizing the V2 peptide that was reported as a critical target in RV144 developed only after the priming immunization with V1V2 DNA. The V2-specific Abs showed several nonneutralizing Fc-mediated functions, including ADCP and C1q binding. Importantly, robust V2-specific Abs were maintained upon boosting with gp145 DNA and gp120 protein coimmunization. In conclusion, priming with DNA expressing the trimeric V1V2 scaffold alters the hierarchy of humoral immune responses to V2 region epitopes, providing a method for more efficient induction and maintenance of V2-specific Env Abs associated with reduced risk of HIV infection.IMPORTANCE The aim of this work was to design and test a vaccine regimen focusing the immune response on targets associated with infection prevention. We demonstrated that priming with a DNA vaccine expressing only the HIV Env V1V2 region induces Ab responses targeting the critical region in V2 associated with protection. This work shows that V1V2 scaffold DNA priming immunization provides a method to focus immune responses to the desired target region, in the absence of immune interference by other epitopes. This induced immune responses with improved recognition of epitopes important for protective immunity, namely, V2-specific humoral immune responses inversely correlating with HIV risk of infection in the RV144 trial.

Dynamic Optimization Method for Broadband ADCP Waveform with Environment Constraints.

Broadband acoustic Doppler current profiler (ADCP) is widely used in agricultural water resource explorations, such as river discharge monitoring and flood warning. Improving the velocity estimation accuracy of broadband ADCP by adjusting the waveform parameters of a phase-encoded signal will reduce the velocity measurement range and water stratification accuracy, while the promotion of stratification accuracy will degrade the velocity estimation accuracy. In order to minimize the impact of these two problems on the measurement results, the ADCP waveform optimization problem that satisfies the environment constraints while keeping high velocity estimation accuracy or stratification accuracy is studied. Firstly, the relationship between velocity or distance estimation accuracy and signal waveform parameters is studied by using an ambiguity function. Secondly, the constraints of current velocity range, velocity distribution and other environmental characteristics on the waveform parameters are studied. For two common measurement applications, two dynamic configuration methods of waveform parameters with environmental adaptability and optimal velocity estimation accuracy or stratification accuracy are proposed based on the nonlinear programming principle. Experimental results show that compared with the existing methods, the velocity estimation accuracy of the proposed method is improved by more than 50%, and the stratification accuracy is improved by more than 22%.

The "Little MonSta" Deep-Sea Benthic, Precision Deployable, Multi-Sensor and Sampling Lander Array.

The "Little MonSta" benthic lander array consists of 8 ROV-deployable (remotely operated vehicle) instrumented lander platforms for monitoring physical and chemical oceanographic properties and particle sampling developed as part of the MMMonKey_Pro program (mapping, modeling, and monitoring key processes and controls in cold-water coral habitats in submarine canyons). The Little MonStas offer flexible solutions to meet the need to monitor marine benthic environments during a historically unprecedented time of climate-driven oceanic change, develop an understanding of meso-scale benthic processes (natural and man-made), and to calibrate geological environmental archives. Equipped with acoustic Doppler current profilers (ADCPs), sediment traps, nylon settlement plates and homing beacons, the compact and upgradable lander platforms can be deployed by ROVs to precise locations in extreme terrains to a water depth of 3000 m. The array allows cluster-monitoring in heterogeneous environments or simultaneous monitoring over wider areas. A proof-of-concept case study was presented from the cold-water coral habitable zone in the upper Porcupine Bank Canyon, where the Little MonStas collected 868.8 h of current speed, direction, temperature, and benthic particulate flux records, as well as 192 particle samples subsequently analyzed for particular organic carbon (POC), lithic sediment, live foraminifera, and microplastics. The potential to upgrade the Little MonStas with additional sensors and acoustic releases offers greater and more flexible operational capabilities.

Analysis and Fine Specificity of the HCMV-Specific Cell-Free and Cell-Associated Antibody-Dependent Cellular Phagocytosis (ADCP) Responses in Lung Transplant Recipients.

Human Cytomegalovirus (HCMV) may cause severe infections in transplant recipients. HCMV-replication can be limited by HCMV-specific antibody responses. The impact of the antibody-dependent cellular phagocytosis (ADCP) on inhibition of HCMV-replication in natural infections has not been clarified. Therefore, we investigated the HCMV-specific ADCP response in a study cohort of lung-transplant recipients (LTRs) with different donor (D) and recipient (R) HCMV-serostatus. Follow-up plasma samples from 39 non/low-viremic and 36 highly viremic (>1000 HCMV copies/mL plasma) LTRs were collected for one (R+ LTRs) or two (D+/R- LTRs) years post-transplantation. The HCMV-specific ADCP responses were assessed by focal expansion assays (FEA) and flow-cytometry. In all LTRs, ADCP responses were detected against HCMV-infected cells and cell-free virions. When measured in fibroblasts as well as with cell-free virus, the HCMV-specific ADPC response was higher in LTRs than in HCMV-seropositive healthy controls. In D+/R- LTRs, a significant ADCP response developed over time after the receipt of an HCMV positive lung, and a level of <19 IE+ cells/focus in the FEA on fibroblasts was associated with further protection from high-level viremia. Taken together, a strong HCMV-specific ADCP response is elicited in transplant recipients, which may contribute to protection from high-level viremia in primary HCMV infection.

The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.

Since the approval of the first monoclonal antibody (mAb) in 1986, a huge effort has been made to guarantee safety and efficacy of therapeutic mAbs. As of July 2021, 118 mAbs are approved for the European market for a broad range of clinical indications. In order to ensure clinical efficacy and safety aspects, (pre-)clinical experimental approaches evaluate the respective modes of action (MoA). In addition to antigen-specificity including binding affinity and -avidity, MoA comprise Fc-mediated effector functions such as antibody dependent cellular cytotoxicity (ADCC) and the closely related antibody dependent cellular phagocytosis (ADCP). For this reason, a variety of cell-based assays have been established investigating effector functions of therapeutic mAbs with different effector/target-cell combinations and several readouts including Fcγ receptor (FcγR)-mediated lysis, fluorescence, or luminescence. Optimized FcγR-mediated effector functions regarding clinical safety and efficacy are addressed with modification strategies such as point mutations, altered glycosylation patterns, combination of different Fc subclasses (cross isotypes), and Fc-truncation of the mAb. These strategies opened the field for a next generation of therapeutic mAbs. In conclusion, it is of major importance to consider FcγR-mediated effector functions for the efficacy of therapeutic mAbs.

Bridging Vaccine-Induced HIV-1 Neutralizing and Effector Antibody Responses in Rabbit and Rhesus Macaque Animal Models.

Studies in animal models are essential prerequisites for clinical trials of candidate HIV vaccines. Small animals, such as rabbits, are used to evaluate promising strategies prior to further immunogenicity and efficacy testing in nonhuman primates. Our goal was to determine how HIV-specific vaccine-elicited antibody responses, epitope specificity, and Fc-mediated functions in the rabbit model can predict those in the rhesus macaque (RM) model. Detailed comparisons of the HIV-1-specific IgG response were performed on serum from rabbits and RM given identical modified vaccinia virus Ankara-prime/gp120-boost immunization regimens. We found that vaccine-induced neutralizing antibody, gp120-binding antibody levels and immunodominant specificities, antibody-dependent cellular phagocytosis of HIV-1 virions, and antibody-dependent cellular cytotoxicity (ADCC) responses against gp120-coated target cells were similar in rabbits and RM. However, we also identified characteristics of humoral immunity that differed across species. ADCC against HIV-infected target cells was elicited in rabbits but not in RM, and we observed differences among subdominantly targeted epitopes. Human Fc receptor binding assays and analysis of antibody-cell interactions indicated that rabbit vaccine-induced antibodies effectively recruited and activated human natural killer cells, while vaccine-elicited RM antibodies were unable to activate either human or RM NK cells. Thus, our data demonstrate that both Fc-independent and Fc-dependent functions of rabbit antibodies can be measured with commonly used in vitro assays; however, the ability of immunogenicity studies performed in rabbits to predict responses in RM will vary depending on the particular immune parameter of interest.IMPORTANCE Nonneutralizing antibody functions have been associated with reduced infection risk, or control of virus replication, for HIV-1 and related viruses. It is therefore critical to evaluate development of these responses throughout all stages of preclinical testing. Rabbits are conventionally used to evaluate the ability of vaccine candidates to safely elicit antibodies that bind and neutralize HIV-1. However, it remained unexplored how effectively rabbits model the development of nonneutralizing antibody responses in primates. We administered identical HIV-1 vaccine regimens to rabbits and rhesus macaques and performed detailed comparisons of vaccine-induced antibody responses. We demonstrated that nonneutralizing HIV-specific antibody responses can be studied in the rabbit model and have identified aspects of these responses that are common, and those that are unique, to rabbits and rhesus macaques. Our findings will help determine how to best utilize preclinical rabbit and rhesus macaque models to accelerate HIV vaccine candidate testing in human trials.

One year of measurements in Alderney Race: preliminary results from database analysis.

The Alderney Race is assumed to have the largest tidal-stream energy potential in the north-western European coastal seas. Interaction of the powerful tidal stream with strong wind, high waves and irregular bathymetry creates hydrodynamic conditions of extreme complexity, with high levels of turbulence. A comprehensive dataset has been created to improve the understanding of physical processes, turbulence, tidal stream and resource variability at the site. The database contains a large amount of oceanographic and meteorological measurements acquired in Alderney Race in 2017-2018. This exceptionally long period of observations (nearly one year) became possible due to modern tools and strategies of data acquisition. The paper presents some significant results from the database analysis. Among many results, we would like to underline the following: (i) a wide range of variability of mean flow and sea state parameters was documented; (ii) exceptionally large values of current velocity (7 m s-1) and significant wave height (8 m) were measured during extreme meteorological conditions; (iii) high-frequency variability of current speed during storm events was also found to be very large, with the standard deviation of velocity reaching 0.3 m s-1 in the bottom boundary layer, and 0.6 m s-1 in the surface layer; and (iv) predominant wind and wave direction relative to the flow impacts the wave height and significantly increases the turbulence kinetic energy of the flow. To our knowledge, this is the largest multi-variable database available on potential tidal energy sites. The results of database analysis can represent a significant advance in environmental conditions and resource characterization and provide advanced information to turbine developers. This article is part of the theme issue 'New insights on tidal dynamics and tidal energy harvesting in the Alderney Race'.

Impact of the expression system on the immune responses to self-assembling protein nanoparticles (SAPNs) displaying HIV-1 V1V2 loop.

The V1V2 loop of the Env protein is a major target for HIV-1 vaccine development because in multiple studies antibodies to this region correlated with protection. Although SAPNs expressed in E. coli elicited anti-V1V2 antibodies, the Env protein is heavily glycosylated. In this study the technology has been adapted for expression in mammalian cells. SAPNs containing a V1V2 loop from a B-subtype transmitter/founder virus were expressed in E. coli, ExpiCHO, and Expi293 cells. Independent of the expression host, particles were well-formed. All SAPNs raised high titers of V1V2-specific antibodies, however, SAPNE.coli induced a mainly anti-V1 response, while SAPNExpiCHO and SAPNExpi293 induced a predominantly anti-V2 response. In an ADCP assay, sera from animals immunized with the SAPNExpiCHO or SAPNExpi293 induced a significant increase in phagocytic activity. This novel way of producing SAPNs displaying glycosylated epitopes could increase the antibody titer, functional activity, and shift the immune response towards the desired pathway.

Description on variability of shelf-edge hydrography and current structure of the South Eastern Arabian Sea during summer and winter monsoons.

The paper describes the hydrography and vertical current structure along the shelf edge of South East Arabian Sea (SEAS) during summer and winter monsoons based on current profiles from moving Acoustic Doppler Current Profiler (ADCP). During summer monsoon, SEAS was characterized by upwelling with low saline water at the surface along the southern sector (8° N to 11° N). During winter, thermal structure was vertically homogeneous in the upper 80 m, and intrusion of low saline Bay of Bengal waters were found up to 14° N. In the southern sector, turbidity was more than the northern sector during winter and summer seasons. ADCP-derived current profiles during summer along 200-m isobath show dominant northward flow in the south, and southeasterly in the north as part of the West India Coastal Current (WICC). A comparison between ADCP current profiles and Ekman currents during summer indicates dominance of remote forcing (coastal Kelvin waves) over the local wind forcing in the 8-9° N sector whereas a combined influence of both remote forcing and wind in the 9-15° N sector. During winter, the direction of surface current reversed and was poleward generally except at the southern sector (7-8° N) where the flow was southwestward. Sector-wise comparison of ADCP and Ekman current showed less influence of wind on current fields throughout the sector except at south; wind has a major role in the current generation, whereas along the 8-15° N sector, the remote forcing dominates over the wind.