Metal clusters can be loaded as cocatalysts on the surface of TiO2 to promote the photocatalytic reduction of CO2. However, the specific mechanism of this reaction is still unclear. This study systematically investigates the performance of metal cluster (M6, M = Au, Ag, Mn, Cu, Sn, Ga, Mo and Bi) as the cocatalytic on the TiO2(101) surface towards the CO2 reduction reaction through density functional theory (DFT) calculations. Metal clusters as co-catalysts supported on TiO2 can improve the light absorption intensity of photocatalysts. Moreover, it was found that these metal clusters significantly improved the electron transport efficiency of TiO2, thereby enhancing the efficiency of photocatalytic CO2 reduction. Cu6@TiO2 showed the highest photocatalytic activity, with a maximum Gibbs free energy change (Delta Gmax) of 0.46 eV. The study also revealed a strong correlation between catalytic activity and the adsorption strength of key intermediates, indicating that enhancing the adsorption differences of key intermediates can improve the efficiency of photocatalysts. In addition, Mn6@TiO2, Cu6@TiO2, Mo6@TiO2, Au6@TiO2, and Ga6@TiO2 can effectively suppress the hydrogen evolution reaction (HER), demonstrating excellent photocatalytic performance and high selectivity. This work provides useful insights into the reduction of CO2 to form single carbon products on TiO2 catalysts loading metal clusters.

The structural parameters and enthalpies of pure ZnSe and different concentrations of V/Mn:ZnSe at high pressures were calculated using the first principles calculation method based on density functional theory. The lattice constants and bond lengths of all the systems decrease under pressure, and the respective phase transition pressures are obtained from the enthalpy-pressure relationship curves, which show that V/Mn elemental doping reduces the phase transition pressure of ZnSe, and the phase transition pressure further decreases with the increase of the doping concentration. The doping formation energies and the elastic constant criterion at atmospheric and high pressures confirm the structural stability of all the systems within the pressures of this study, and the pugh ratio confirms that they are all ductile structures.The results of electrical properties study show that at atmospheric pressure, all V:ZnSe systems have metallic properties, and a metal to semiconductor transition occurs at high pressure when the doping concentration is 12.5%. However, the Mn:ZnSe systems are semiconductors at both atmospheric and high pressures. Pressure significantly influences the degeneracy and position of the impurity bands: the impurity bands of V:ZnSe move toward higher energy under pressure, while the impurity bands of the Mn:ZnSe system shift toward lower energy. The element doping concentration also affects the d orbital degeneracy of V/Mn:ZnSe under atmospheric pressure, the degeneracy of V/Mn-d orbital decreases with the increase in doping concentration. Under high pressure, the degeneracy of the V/Mn-d orbital decreases further when the doping concentration is 3.13%, but the degeneracy is enhanced when the doping concentration is 6.25 and 12.5%. Doping can effectively change the phase transition pressure of ZnSe, and the pressure can effectively modulate the properties of this material.

BACKGROUND:The success of passive immunotherapies targeting Calcitonin gene-related peptide (CGRP) for managing migraine has prompted our efforts towards developing an active immunotherapy that induces the production of endogenous antibodies against CGRP. Achieving efficacious antibody titers via immunization could provide a more convenient and cost-effective treatment alternative to anti-CGRP monoclonal antibody (mAb) therapies. However, immunization against endogenous CGRP faces multiple challenges such as breaking immune tolerance, inducing sufficient antibody titers, and avoiding immune response-associated toxicity. METHODS:Synthetic peptide immunogens formulated in adjuvants were delivered intramuscularly. Serum samples were collected post immunization and used to measure antibody titers as well as for the isolation of antibodies specific to CGRP. Antibodies were characterized for their binding affinities and specificities. The capsaicin-induced increase in dermal blood flow model was used in rats for the assessment of the pharmacodynamic effect of immunization. RESULTS:Here we demonstrate that a peptide-based active immunotherapy designed to induce antibodies against CGRP promotes robust antibody titers across preclinical species. Characterization of the immune response strongly suggests that this peptide immunogen primarily stimulates a humoral response and only induced CGRP-specific antibodies. Antibodies produced by immunization are primarily IgG1 and demonstrate binding and activity potencies similar to marketed monoclonal antibodies against CGRP. Finally, immunization demonstrates in vivo efficacy in a rat pharmacodynamic model. CONCLUSION:Our results strongly suggest that a peptide-based active immunotherapy against CGRP could provide an affordable and convenient therapeutic for the prevention of migraine.

Background:Authorized COVID-19 vaccines require boosters for continued protection; however, the lack of cross-platform compatible boosters creates practical challenges to keeping populations protected. Methods:This Phase 3, multicenter, international, randomized, active-controlled trial compared UB-612 as a third-dose heterologous booster to BNT162b2, ChAdOx1-S, or BBIBP-CorV homologous boosters in healthy subjects aged ≥16 years. Participants were randomly assigned 1:1 to receive a single intramuscular injection of UB-612 or an active comparator matching the primary dose, and were stratified for age, sex, N-protein seropositivity, and time since the last dose of their primary series COVID-19 vaccination. The primary objective was to show non-inferiority of neutralizing antibody geometric mean titer (GMT) against live SARS-CoV-2 Wuhan strain after boosting with UB-612 or each of the licensed platform vaccines. Secondary and exploratory objectives covered short and long-term antibody responses. The safety analysis addressed subject and investigator reported adverse events. The study was registered on ClinicalTrials.gov, NCT05293665, and completed on September 12, 2023. Findings:Between March 22 and September 9, 2022, 469 subjects received UB-612 as a heterologous booster, and 467 received BNT162b2 (n = 204), ChAdOx1-S (n = 95), or BBIBP-CorV (n = 168) as homologous boosters. Over 90% of all subjects were positive for N-protein antibody at baseline. When compared to the respective homologous booster response, UB-612 stimulated Wuhan and Omicron BA.5 neutralizing antibody responses that were non-inferior, thus meeting all primary and secondary immunogenicity endpoints of the study. Importantly, UB-612 demonstrated superiority in neutralizing antibody GMT and seroresponse rates compared to ChAdOx1-S and BBIBP-CorV. UB-612 was also effective in stimulating neutralizing antibodies against a more recent Omicron XBB1.5 strain. Long-term immunity analysis through 6- and 12-month follow-ups favored UB-612 over ChAdOx1-S and BBIBP-CorV and supported comparable immunity to BNT162b2. All vaccines were well tolerated and had similar safety profiles. Interpretation:In a pivotal Phase 3 study, UB-612 demonstrated the potential for broad use as a cross-platform heterologous booster, restoring protective immunity in adults previously vaccinated with mRNA, adenovirus-vectored, or inactivated virus-based COVID-19 vaccines. Funding:The study was co-funded by the Coalition for Epidemic Preparedness Innovations (CEPI) and Vaxxinity.

SnO2,as an important conductive oxide,can be used in solar cells,electrodes,oxidation catalysts,etc.The electronic structuresand ionic radii of Sn4+and Pb4 are similar,and doping Pb into the crystal structure of SnO2 can change its optoelectronic properties without destroying the structure.Pressure to change the lattice structure and electronic band gap of materials can effectively enhance the material properties.To investigate the effects of elemental doping and pressure on the structural properties of SnO2,the structural phase transitions and electronic band gap changes of 10％Pb-doped and 25％Pb-doped SnO2 under high pressure were investigated.Pure SnO2,10％Pb-doped and 25％Pb-doped SnO2 samples were prepared hydrothermal.Scanning electron microscopy showed that the samples were composed of multiple nanorods arranged in the center of the dispersion,and the whole was in the shape of a flower;X-ray diffraction showed that the samples were of a tetragonal rutile structure(space group P42);and the EDS spectra showed that the Pb was completely doped in the SnO2 lattice.The effects of different ratios of Pb doping on the high-voltage structure and electrical properties of SnO2 were investigated using a diamond pressure cavity combined with in situ Raman spectroscopy.Raman spectroscopy results show that there are four Raman vibrational modes of SnO2 at ambient pressure,which are B1g(88 cm 1),Eg(480 cm 1),A1g(639 cm 1)and B2g(775 cm 1).When the system pressure increases to 14 GPa,the Eg peak splits,a new peak appears at 563 cm-1 and SnO2 changes from a tetragonal rutile structure to a high-pressure CaCl2-type structure;the two Raman peaks at A1g and 576 cm-1 of 10％Pb-doped SnO2 gradually broaden with the increase of the pressure,and then merge to form a packet-like peak at 13 GPa,the degree of atomic disorder on the surface of the crystal increases,the symmetry decreases,the B1g mode changes to the A1g mode,the structural phase transition begins to appear,and the system changes to amorphous when the pressure increases to 25 GPa;the Raman peaks of 25％Pb-doped SnO2 appear at 190 and 775 cm-1,respectively,with the Pb4+and B2g peaks,and the intensity of the Eg peak becomes weaker when the pressure reaches 10 GPa,the two Raman peaks at 576 cm-1 and A1g merge,the structural phase transition occurs,and amorphization occurs at 25.4 GPa.Using first-principles calculations to study the electrical properties of pure SnO2 and 10％Pb-doped SnO2 under pressure results show that:increased system pressure will make the forbidden band width of pure SnO2 from 0.645 to 1.759 eV,the electrons are more difficult to jump to the conduction band,the electrical conductivity is reduced;at the same time,doping will make the Pb into the crystal lattice to form defects,resulting in an increase in the density of defects in the vicinity of the valence band,valence band energy level decreases,the conductivity is enhanced,but the increase in system pressure does not change the conductivity of doped SnO2.This study provides new ideas in the field of SnO2 elemental doping.It enriches the study of the properties of SnO2 under extreme conditions by combining it with in situ high-pressure technology.

In recent years SnO has been increasingly used in optical and electrical applications. Raman spectroscopic in situ tests and first principle calculations were applied to investigate the structural and electronic properties of SnO under high pressure. conditions to broaden the application scope of SnO, The results of the characterization of SnO are as follows, the scanning electron microscopy results show that the selected SnO samples are lamellar stacks with transverse dimensions, and the whole is in the shape of a flower, the X-ray diffraction patterns indicate that the crystal structure of the SnO samples is a tetragonal crystal system structure (space group P4/nmm) at room temperature and pressure. The structural properties of SnO samples. under high pressure have been investigated using Mao-Bell Diamond anvil cell and in situ Raman spectroscopy, and the results show that there are four Raman vibrational modes (A(1g), B-1g, E-1g,E- and E-2g) of SnO at atmospheric pressure. A(1g), characterizes the vibration parallel to thez-axis in the plane of the Sn-Sn bond; B-1g,, characterizes the vibration parallel to thez-axis in the plane of the O-O bond, and E, characterizes the vibration of Sn- atoms in the plane of the intra-layer polarization, which are located near the wave numbers 211, 350, 113, and 460 cm, respectively, with the peaks 113 and 211 em heing SnO characteristic peaks. During the pressurization of the Sn-O sample system to 12.5 GPa, the pressure causes Sn's intermolecular and atomic spacing to decrease, resulting in the shortening of the Sn O bond length. When the atoms undergo telescopic vibration, the shortened bond length increases bond energy. Thus, the active Raman vibrational modes (E), and A) shift toward the high frequency direction, As the system pressure continues to increase, the lattice is distorted, the inelastic scattering intensity decreases, and the peaks broaden, when the pressure is increased to 8 GPa. the vibrational mode peaks of Es, and A, near 125 and 216 cm decrease dramatically, when the pressure is increased to 10 GPa, the two characteristic peaks disappear completely, and it is inferred that amorphization of the substance occurs in the non-hydrostatic pressure environment at 8-10 GPa, When the system was pressurized to 12.5 GPa, no new peaks still appeared in the spectra, indicating that the amorphous state was stable under high pressure. Subsequently, the system was depressurized, and theE, and A modes of SnO reappeared after depressurization to 3 GPa, indicating that the sample regained the crystal structure at low pressure, The intensity of the unloading to atmospheric pressure characteristic peaks are located at 110 and 209 cm. respectively, in agreement with the unpressurized data, proving that the high pressure phase transition behavior of SnO is reversible. To further understand the effect of pressure on the electrical properties of SnO, the electronic properties of SnO at atmospheric pressure and experimentally speculated amorphization pressure (8 GPa) were calculated using the first principles approach. The effect of pressure on the electrical conductivity of SnO was investigated through the change in band gap width of SnO before and after amorphization. The results show that SnO is indirect bandgap semiconductor with a bandgap of 0. 43 eV at atmospheric pressure, there is no overlap of the density of states near the Fermi energy level, and SnO displays metallic properties at 8 GPa when the material is metalized due to the overlap of the density of states of the O-p. Sns. and Sn-p orbitals of SnO at the Fermi energy level, which leads to the closure of the bandgap. In this paper, the Raman spectroscopic and electrical properties of SnO under high pressure environments have been investigated, enriching the study of the physicochemical properties of this material under extreme conditions. The results of this paper further improve the investigation of the structural and electrical properties of SnO under high pressure, expanding the scope of its research in the field of high pressure, and the results will be helpful for the experimental study of SnO under high pressure and its application under high pressure.

BACKGROUND:An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV vaccine with matching envelope (Env) immunogens. METHODS:HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18-50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one gag p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime-boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA-protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT03409276) and is closed to new participants. FINDINGS:Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime-boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime-boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime-boost and coadministration groups (eg, 20 [95%] of 21 in the prime-boost group vs 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] vs nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime-boost group vs 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] vs 12 [57%]), and myalgia (four [40%] and 13 [62%] vs ten [48%]), mostly of mild or moderate severity. INTERPRETATION:Both vaccine regimens were safe, warranting evaluation in larger trials. FUNDING:US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.

ZnSe semiconductor material is an important raw material for preparing optoelectronic devices and photocatalytic reaction catalysts. The monomer material exhibits deterioration under strong light and electron-hole recombination. In this study, ZnSematerials were prepared by element doping, and the optical and structural properties of ZnSe enhanced by element doping were studied and compared with those of monomer materials. Pure ZnSe and Mn/Zn with doping ratios of 5%, 10%, 15%, and 20% were prepared by the hydrothermal method in the laboratory to compare the morphology, structure, light absorption, and catalytic performance of the composite materials. The results showed that the sample with a doping ratio of 10% had the highest crystallinity, the least impurities, and the best catalytic performance. Subsequently, the high-pressure structural phase transformation behavior of pure ZnSe and samples doped with 10% Mn/Zn was investigated by in-situ Raman spectroscopy using Diamond Anvil Cell to explore the effect of element doping on the structural properties of the samples. The results are as follows: (1) Scanning electron microscope (SEM) images show that the morphology of the ZnSe sample prepared with Mn element is spherical and similar to the pure sample. Small particles are on the surface of the spherical particles, and with the increase of Mn addition, more substances are loaded on the surface. (2) X-ray diffraction (XRD) patterns show that the structure of the ZnSe sample is a cubic zinc blende structure. With the increase of Mn addition, the characteristic peak of MnSe in the sample is enhanced and the formation of impurity MnO2 is more completed. The sample with a doping ratio of 10% has a high ZnSe crystallinity and a low impurities formation. (3) Solid-state ultraviolet diffuse reflectance (UV-Vis) results show that the sample with a doping ratio of 10% has the maximum light absorption edge and the smallest bandgap width of 1.65 eV. (4) The results of the photocatalytic experiment show that the sample with a doping ratio of 10% has the highest efficiency in catalyzing the degradation of methyl orange, with a degradation rate of 85.4% in 6 hours. The study demonstrates that the ZnSe composite material doped with 10% Mn element has the best relative optical absorption and catalytic performance. The high-pressure phase transition of ZnSe samples and samples with a doping ratio of 10% were investigated using Diamond Anvil Cells combined with in-situ Raman spectroscopy. The results show that: (1) The LO phonon mode of pure ZnSe disappears at a pressure of 12.3 GPa, and the TO phonon mode disappears at a pressure of 20.8 GPa. No new peaks are generated during the entire pressure process, indicating a high-pressure behavior of the pure ZnSe phase transition from the zincblende phase to the rocksalt phase. (2) The TO phonon mode of the composite material splits at 6.9 GPa, and a new peak appears at 208 cm(-1) at 8.0 GPa, indicating that some samples transform from the zincblende phase to the wurtzite phase at this pressure. The peak of the wurtzite phase disappears at 10.8 GPa, and the system undergoes a phase transition from the wurtzite phase to the rocksalt phase. When the pressure is increased to 18.8 GPa, the LO phonon mode is very weak and almost disappears, indicating that the zincblende phase in the system has completely transformed into the rocksalt phase. This study investigated the photo-catalytic performance and phase transition behavior of ZnSe under different conditions and explored the effects of different doping ratios on the photo-catalytic performance of ZnSe, determining that the sample with a doping ratio of 10% is the best composite material, which enriches the diversity of the physical and chemical properties of ZnSe under extreme conditions.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a "high -risk" patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide -based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD. VXX-401 is designed to trigger a safe humoral immune response against PCSK9, resulting in the production of endogenous antibodies and a subsequent 30-40% reduction in blood LDL-C. In this article, VXX-401 demonstrates robust immunogenicity and sustained serum LDL-C-lowering effects in nonhuman primates. In addition, antibodies induced by VXX-401 bind to human PCSK9 with high affinity and block the inhibitory effect of PCSK9 on LDL-C uptake in a hepatic cell model. A repeat -dose toxicity study conducted in nonhuman primates under good laboratory practices toxicity indicated a suitable safety and tolerability profile, with injection site reactions being the main findings. As a promising safe and effective LDL-C-lowering therapy, VXX-401 may represent a broadly accessible and convenient option to treat hypercholesterolemia and prevent ASCVD.

The vaccine elicitation of HIV-neutralizing antibodies with tier-2-neutralization breadth has been a challenge. Here, we report the isolation and characteristics of a CD4-binding site specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent gp120 DNA prime-protein boost vaccine. HmAb64 derived from heavy chain variable germline gene IGHV1-18, light chain germline gene IGKV1-39, and had a 3rd heavy chain complementarity determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 21 (10%), including tier-2 neutralization resistant strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 bound to a conformation between prefusion closed and occluded open forms of envelope trimer, using both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4-binding site. A gp120 subunit-based vaccine can thus elicit an antibody capable of tier 2-HIV neutralization.

So far, overcoming thermal quenching remains a huge challenge in the application of phosphor materials. The intervalence charge transfer (IVCT) state has an inestimable role in the compensation of antithermal-quenching effects and is widely used in the research of applications in optical temperature sensing, yet little study has been reported on its modulation of thermal quenching properties. In this contribution, the thermal quenching properties of praseodymium-activated solid-solution substituted GdNb1-xTaxO4 phosphors were investigated systematically for the inaugural time from the perspective of IVCT energy level positions. According to the empirical formula, the IVCT level positions in the phosphor increase sequentially from 32960.71 cm-1 to 33442.15 cm-1, the DFT calculates the extension of the substrate band gap from 3.6408 eV to 4.3066 eV, and the contributing energy level of the conduction band is determined. The variation in the position of the IVCT energy level explains the alteration of the luminescence intensity at room temperature for different composition phosphor 3P0 and 1D2 energy levels. More particularly, it was analyzed that in the variable temperature spectra, x = 0-0.75 exhibited different degrees of efficient antithermal-quenching properties at 303-523 K, while no antithermal-quenching was presented at x = 1. By analyzing the IVCT energy level position and other influencing factors such as band gap, the feasibility of the IVCT energy level position as a competing model for the compensation and quenching channels is established, and the internal mechanism of regulating thermal quenching property is revealed. Effective control of the phosphor resistance to thermal quenching performance was achieved, which directly determines whether enhanced or diminished thermal quenching can be obtained. This finding provides a new effective strategy for the tuning of thermal quenching luminescence of Pr3+-doped Nb/Ta system phosphors.

Two-dimensional layered molybdenum trioxide (MoO3) holds significant importance in optoelectronics owing to its unique anisotropic structure and optical properties. Given that changes in structure can profoundly impact physical characteristics, it becomes imperative to explore new properties by means of acquiring different structures. Here, we report the irreversibility of structural evolution and optical properties of molybdenum trioxide under high pressure. The quenched MoO3 possesses a stable high-pressure phase MoO3-II, a narrowed bandgap (reduced by ∼25%) and a strong optical absorption at visible to infrared region compared to the initial low-pressure phase α-MoO3. These findings will facilitate the exploring of high-pressure phase materials under ambient conditions.

The fusion peptide (FP) and the Trp-rich membrane proximal external region (MPER) display membrane activity during HIV-1 fusion. These domains are highly conserved in the envelope glycoprotein (Env) and, consequently, antibodies targeting these regions block entry of divergent HIV strains and isolates into target cells. With the aim of recovering concurrent responses against the membrane-active Env domains, we have produced hybrid peptides that connect FP and MPER sequences via flexible aminohexanoic acid tethers, and tested their potential as immunogens. We demonstrate that liposome-based formulations containing FP-MPER hybrid peptides could elicit in rabbits, antibodies with the binding sequence specificity of neutralizing antibodies that engage with the N-terminal MPER sub-region. Determination of the thermodynamic parameters of binding using the Fab 2F5 as an N-terminal MPER antibody model, revealed that the hydrophobic interaction surface for epitope engagement appears to be optimal in the FP-MPER hybrid. In general, our data support: i) the use of liposomes as carriers for membrane active peptides; ii) the capacity of these liposome-based vaccines to focus humoral responses to N-terminal MPER epitopes; and iii) the need to include lipid membranes in immunogens to elicit such specific responses.

Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein–peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and antibody-dependent NK cell activation (ADNKA) assays. In cynomolgus macaques, UB-612 induced potent serum-neutralizing, RBD-specific IgG binding, ACE2 binding-inhibition antibodies, and antibodies with Fc-mediated effector functions in ADMP and ADNKA assays. Additionally, immunized animals developed mucosal antibodies in bronchoalveolar lavage fluids (BAL). The level of mucosal or serum ADMP and ADNKA antibodies was found to be UB-612 dose-dependent. Our results highlight that the novel subunit UB-612 vaccine is a potent B-cell immunogen inducing polyfunctional antibody responses contributing to anti-viral immunity and vaccine efficacy.

The highly transmissible Omicron variant has caused high rates of breakthrough infections among vaccinated and convalescent individuals. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increases neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1 and BA.2 variants, respectively. Based on the RBD protein binding antibody responses, we estimated a ∼95% efficacy against symptomatic COVID-19 caused by the ancestral strain after a UB-612 booster. Our results support UB-612 vaccine as a potent booster against current and emerging SARS-CoV-2 variants. ### Competing Interest Statement FG, SW, LW, MMH, TM and AR are employees at Vaxxinity, Inc, Dallas, TX, USA. CYW, WJP, and HL are employees at United Biomedical Inc Asia, Taipei, Taiwan.

Omicron, a highly transmissible SARS-CoV-2, emerged in November 2021. The high mutation rates within spike protein of Omicron raised concerns about increased breakthrough infections among the vaccinated. We tested cross-reactivity of antibodies induced by UB-612 against Omicron and other variants. After 2 doses, UB-612 elicited low levels of neutralization antibodies against ancestral virus and Omicron. A booster dose delivered 7-9 months after primary vaccination dramatically increased antibody levels, with only a 1.4-fold loss in neutralization titer against Omicron compared to the ancestral strain. Using a model bridging vaccine efficacy with ancestral virus RBD binding antibody responses, predicted efficacy against symptomatic COVID-19 after UB-612 booster is estimated at 95%. UB-612 is anticipated to be a potent booster against current and emerging SARS-CoV-2 variants. One-Sentence Summary UB-612 booster induced broadly neutralizing antibodies against Omicron and is presumed to be protective against COVID-19.

Since publishing our original reports on the safety and immunogenicity of a polyvalent DNA prime-protein boost HIV vaccine (PDPHV) which elicited high titer antibody responses with broad specificity, neutralizing activities to multiple HIV-1 subtypes, as well as poly-functional T cell responses, accumulated findings from other HIV vaccine studies indicated the important roles of Ig isotype distribution, Fc medicated functions and the persistence of memory immune responses which were not studied in previous PDPHV related reports. The current report provides further detailed characterization of these parameters in human volunteers receiving the PDPHV regimen. Antibody responses were assessed using IgG isotype and gp70-V1V2-binding ELISAs, peptide arrays, and antibody-dependent cellular cytotoxicity (ADCC) assays. B cell ELISPOT was used to detect gp120-specific memory B cells. Our results showed that the gp120-specific antibodies were primarily of the IgG1 isotype. HIV-1 envelope protein variable regions V1 and V2 were actively targeted by the antibodies as determined by specific binding to both peptide and V1V2-carrying scaffolds. The antibodies showed potent and broad ADCC responses. Finally, the B cell ELISPOT analysis demonstrated persistence of gp120-specific memory B cells for at least 6 months after the last dose. These data indicate that broadly reactive binding Abs and ADCC responses as well as durable gp120-specific memory B cells were elicited by the polyvalent heterologous prime-boost vaccination regimens and showed great promise as a candidate HIV vaccine.

Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted with CD34+ hematopoietic stem cells, followed by mucosal challenge with an HIV-1 infectious molecular clone expressing the envelope of a tier 2 resistant HIV-1 strain. Treatment with anti-V1V2 mAb 2158 or anti-V3 mAb 2219 did not prevent infection, but V3 mAb 2219 displayed a superior potency compared to V1V2 mAb 2158 in reducing virus burden. While these mAbs had no or weak neutralizing activity and elicited undetectable levels of antibody-dependent cellular cytotoxicity (ADCC), V3 mAb 2219 displayed a greater capacity to bind virus- and cell-associated HIV-1 envelope and to mediate antibody-dependent cellular phagocytosis (ADCP) and C1q complement binding as compared to V1V2 mAb 2158. Mutations in the Fc region of 2219 diminished these effector activities in vitro and lessened virus control in humanized mice. These results demonstrate the importance of Fc functions other than ADCC for antibodies without potent neutralizing activity.