Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or ß-Sheet Conformations on Time of SIVmac251 Acquisition.

The monoclonal antibodies (MAbs) NCI05 and NCI09, isolated from a vaccinated macaque that was protected from multiple simian immunodeficiency virus (SIV) challenges, both target an overlapping, conformationally dynamic epitope in SIV envelope variable region 2 (V2). Here, we show that NCI05 recognizes a CH59-like coil/helical epitope, whereas NCI09 recognizes a ß-hairpin linear epitope. In vitro, NCI05 and, to a lesser extent, NCI09 mediate the killing of SIV-infected cells in a CD4-dependent manner. Compared to NCI05, NCI09 mediates higher titers of antibody-dependent cellular cytotoxicity (ADCC) to gp120-coated cells, as well as higher levels of trogocytosis, a monocyte function that contributes to immune evasion. We also found that passive administration of NCI05 or NCI09 to macaques did not affect the risk of SIVmac251 acquisition compared to controls, demonstrating that these anti-V2 antibodies alone are not protective. However, NCI05 but not NCI09 mucosal levels strongly correlated with delayed SIVmac251 acquisition, and functional and structural data suggest that NCI05 targets a transient state of the viral spike apex that is partially opened, compared to its prefusion-closed conformation. IMPORTANCE Studies suggest that the protection against SIV/simian-human immunodeficiency virus (SHIV) acquisition afforded by the SIV/HIV V1 deletion-containing envelope immunogens, delivered by the DNA/ALVAC vaccine platform, requires multiple innate and adaptive host responses. Anti-inflammatory macrophages and tolerogenic dendritic cells (DC-10), together with CD14+ efferocytes, are consistently found to correlate with a vaccine-induced decrease in the risk of SIV/SHIV acquisition. Similarly, V2-specific antibody responses mediating ADCC, Th1 and Th2 cells expressing no or low levels of CCR5, and envelope-specific NKp44+ cells producing interleukin 17 (IL-17) also are reproducible correlates of decreased risk of virus acquisition. We focused on the function and the antiviral potential of two monoclonal antibodies (NCI05 and NCI09) isolated from vaccinated animals that differ in antiviral function in vitro and recognize V2 in a linear (NCI09) or coil/helical (NCI05) conformation. We demonstrate that NCI05, but not NCI09, delays SIVmac251 acquisition, highlighting the complexity of antibody responses to V2.

Sex-biased gene expression in antennae of Drosophila suzukii.

Drosophila suzukii differs from other members of the genus Drosophila in its host preference and oviposition behavior. The flies are attracted to ripening fruits, and females have a serrated ovipositor enabling eggs to be laid inside the fruit. In addition to its huge economic impact, its unique chemoecological, morphological, and physiological characteristics have garnered considerable research interests. In this study, we analyzed D. suzukii antennal transcriptomes to identify sex-biased genes by comparison of differential gene expressions between male antennae (MA) and female antennae (FA). Among 13,583 total genes of the fly genome, 11,787 genes were expressed in either MA or FA. There are only 132 genes (9 in MA, 7 in FA, and 116 in both, FPKM >1) were expressed in antennae exclusively, and 2,570 genes (9 in MA, 0 in FA, and 2,561 in both) were enriched in antennae containing 185 and 113 sex-biased genes in MA and FA, respectively. Interestingly, many immune-related genes were highly expressed in MA, whereas several chemosensory genes were at high rank in FA. We identified 27 sex-biased chemosensory genes including odorant and gustatory receptors, odorant-binding proteins, chemosensory proteins, ionotropic receptors, and cytochrome P450s, and validated the gene expressions using quantitative real-time PCR. The highly expressed sex-biased genes in antennae are likely involved in the fly specific mating, host-finding behaviors, or sex-specific functions. The molecular results demonstrated here will facilitate to find the unique chemoreception of D. suzukii, as well as on the development of new management strategies for this pest.

Morphological and functional heterogeneity in olfactory perception between antennae and maxillary palps in the pumpkin fruit fly, Bactrocera depressa.

The morphology and ultrastructure of the olfactory sensilla on the antennae and maxillary palps were investigated through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and their responses to five volatile compounds were measured using electroantenogram (EAG) and electropalpogram (EPG) techniques in the pumpkin fruit fly, Bactrocera depressa (Shiraki; Diptera: Tephritidae). Male and female B. depressa displayed distinct morphological types of olfactory sensilla in the antennae and maxillary palps, with predominant populations of trichoid, basiconic, and coeloconic sensilla. Basiconic sensilla, the most abundant type of olfactory sensilla in the antennae, could be further classified into two different types. In contrast, the maxillary palps exhibited predominant populations of a single type of curved basiconic sensilla. High-resolution SEM observation revealed the presence of multiple nanoscale wall-pores on the cuticular surface of trichoid and basiconic sensilla, indicating that their primary function is olfactory. In contrast, coeloconic sensilla displayed several longitudinal grooves around the sensillum peg. The TEM observation of individual antennal olfactory sensilla indicates that the basiconic sensilla are thin-walled, while the trichoid sensilla are thick-walled. The profile of EAG responses of male B. depressa was different from their EPG response profile, indicating that the olfactory function of maxillary palps is different from that of antennae in this species. The structural and functional variation in the olfactory sensilla between antennae and maxillary palps suggests that each plays an independent role in the perception of olfactory signals in B. depressa.

DNA end recognition by the Mre11 nuclease dimer: insights into resection and repair of damaged DNA.

The Mre11-Rad50-Nbs1 (MRN) complex plays important roles in sensing DNA damage, as well as in resecting and tethering DNA ends, and thus participates in double-strand break repair. An earlier structure of Mre11 bound to a short duplex DNA molecule suggested that each Mre11 in a dimer recognizes one DNA duplex to bridge two DNA ends at a short distance. Here, we provide an alternative DNA recognition model based on the structures of Methanococcus jannaschii Mre11 (MjMre11) bound to longer DNA molecules, which may more accurately reflect a broken chromosome. An extended stretch of B-form DNA asymmetrically runs across the whole dimer, with each end of this DNA molecule being recognized by an individual Mre11 monomer. DNA binding induces rigid-body rotation of the Mre11 dimer, which could facilitate melting of the DNA end and its juxtaposition to an active site of Mre11. The identified Mre11 interface binding DNA duplex ends is structurally conserved and shown to functionally contribute to efficient resection, non-homologous end joining, and tolerance to DNA-damaging agents when other resection enzymes are absent. Together, the structural, biochemical, and genetic findings presented here offer new insights into how Mre11 recognizes damaged DNA and facilitates DNA repair.

Species-Specific Interactions between Plant Metabolites and Insect Juvenile Hormone Receptors.

Because juvenile hormone (JH) controls insect development and its analogs are used as insecticides, juvenile hormone disruptors (JHDs) represent potential sources from which novel pesticides can be developed. Many plant species harbor JHD activity, which has previously been attributed plant secondary metabolites (i.e., diterpenes) that disrupt insect development by interfering with the JH-mediated heterodimer formation of insect juvenile receptor complexes. The results of the present study indicate that plant JHD activity is also concentrated in certain plant groups and families and that plant metabolites have insect group-specific activity. These findings suggest that reciprocal diversification has occurred between plants and insects through the evolution of the plant metabolites and JH receptors, respectively, and that plant metabolites could be developed into insect group-specific pesticides with limited effects on non-target species.

Diagnostic Usefulness of Varicella-Zoster Virus Real-Time Polymerase Chain Reaction Analysis of DNA in Saliva and Plasma Specimens From Patients With Herpes Zoster.

Background: We evaluated the diagnostic usefulness of polymerase chain reaction (PCR) analysis for detecting varicella-zoster virus (VZV) infection and reactivation of VZV, using DNA extracted from saliva and plasma specimens obtained from subjects with suspected herpes zoster and from healthy volunteers during stressful and nonstressful conditions. Methods: There were 52 patients with a diagnosis of herpes zoster (group 1), 30 with a diagnosis of zoster-mimicking disease (group 2), and 27 healthy volunteers (group 3). Saliva and plasma samples were evaluated for VZV DNA by real-time PCR analysis. Results: Among patients with suspected herpes zoster (ie, patients in groups 1 and 2), the sensitivity of PCR analysis of salivary DNA for detecting VZV (88%; 95% confidence interval [CI], 74%-95%) was significantly higher than that of PCR analysis of plasma DNA (28%; 95% CI, 16%-44%; P < .001), whereas the specificity of PCR analysis of salivary DNA (100%; 95% CI, 88%-100%) was similar to that of PCR analysis of plasma DNA (100%; 95% CI, 78%-100%; P > .99). VZV DNA was not detected in saliva and plasma samples from group 3 (0%; 95% CI, 0%-14%). Conclusions: Real-time PCR analysis of salivary DNA is more sensitive than that of plasma DNA for detecting VZV among patients with suspected herpes zoster. We found no subclinical reactivation of VZV in group 3 following exposure to common stressful conditions.

Conifer Diterpene Resin Acids Disrupt Juvenile Hormone-Mediated Endocrine Regulation in the Indian Meal Moth Plodia interpunctella.

Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding. Plant extracts from conifers, especially members of the Pinaceae, exhibited strong interfering activity, and four active interfering DRAs (7α-dehydroabietic acid, 7-oxodehydroabietic acid, dehydroabietic acid, and sandaracopimaric acid) were isolated from roots of the Japanese pine Pinus densiflora. The four isolated DRAs, along with abietic acid, disrupted the juvenile hormone-mediated binding of P. interpunctella Met and SRC, although only 7-oxodehydroabietic acid disrupted larval development. These results demonstrate that DRAs may play a defensive role against herbivorous insects via insect endocrine-disrupting activity.

Duty-Related Trauma Exposure and Posttraumatic Stress Symptoms in Professional Firefighters.

Firefighters commonly encounter traumatic events during duty hours. The purpose of this study was to investigate the characteristics of duty-related trauma as risk factors for posttraumatic stress disorder in professional firefighters. A sample of 212 firefighters participated in the study and completed self-reported questionnaires. Potentially traumatic events (PTE) were assessed using a list of 17 traumatic event types. The posttraumatic stress symptoms (PTSS) were measured by the Impact of Event Scale-Revised (Lim et al., 2009; Weiss, 2007). A higher score for the composite index, which reflects both multiple PTE and peritraumatic suffering, increased the odds for significant PTSS after adjusting for age, sex, marital status, education, numbers of years worked, childhood trauma, and depressive symptoms (adjusted odds ratio [AOR] = 2.26, p = .001, Cohen's d = 0.20). Furthermore, indirect (AOR = 1.93, p = .009, Cohen's d = .16) and colleague-related PTE (AOR = 1.97, p = .037, Cohen's d = .16) showed significant associations with PTSS. It is noteworthy that the combination of multiple PTE and peritraumatic suffering was more predictive of PTSS than either factor alone. Our findings also suggest that daily work exposure to indirect PTE may contribute to the occurrence of PTSS among professional firefighters.

The herbal-derived honokiol and magnolol enhances immune response to infection with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA).

The emergence of antibiotic resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune-modulating agent for preventing S. aureus infection. In this study, we found that herbal medicines, honokiol and magnolol, caused a significant cellular immune modulatory effect during S. aureus infection. In mouse macrophages, these compounds drove upregulation of an antioxidant effect in response to S. aureus, resulting in a dampened total cellular reactive oxygen species (ROS) production and decreased production of inflammatory cytokines/chemokines, whereas honokiol induced increased types I and III interferon messenger RNA (mRNA) expression levels in response to MSSA infection. Moreover, the internalization of S. aureus by human alveolar epithelial cells was inhibited by these compounds. Furthermore, honokiol and magnolol treatment promoted a delay in killing during MSSA infection in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In conclusion, honokiol and magnolol may be considered as attractive immune-modulating treatment for S. aureus infection.

In vitro and in vivo antimicrobial efficacy of natural plant-derived compounds against Vibrio cholerae of O1 El Tor Inaba serotype.

In this study, we investigated antibacterial activities of 20 plant-derived natural compounds against Gram-negative enteric pathogens. We found that both flavonoids and non-flavonoids, including honokiol and magnolol, possess specific antibacterial activities against V. cholerae, but not against other species of Gram-negative bacterium which we tested. Using various antibacterial assays, we determined that there was a dose-dependent bactericidal and biofilm inhibitory activity of honokiol and magnolol against Vibrio cholerae. In addition to antibacterial activities, these molecules also induced an attenuating effect on reactive oxygen species (ROS) production and pro-inflammatory responses generated by macrophages in response to lipopolysaccharides (LPS). Additionally, Caenorhabditis elegans lethality assay revealed that honokiol and magnolol have an ability to extend a lifespan of V. cholerae-infected worms, contributing to prolonged survival of worms after lethal infection. Altogether, our data show for the first time that honokiol and magnolol may be considered as attractive protective or preventive food adjuncts for cholera.

Luteimicrobium xylanilyticum sp. nov., isolated from the gut of a long-horned beetle, Massicus raddei.

A novel strain, designated W-15(T), was isolated from the gut of a long-horned beetle, Massicus raddei, collected in South Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strains belonged to the suborder Micrococcineae. Strain W-15(T) was most closely related to Luteimicrobium album RI148-Li105(T) (97.9 % similarity). Strain W-15(T) was Gram-stain-positive, rod- and coccus-shaped and non-motile. Growth was observed at 15-37 °C, at pH 4.5-8.5 and in the presence of 0-5.0 % NaCl. The cell-wall peptidoglycan of the strain was A4α (l-Lys-d-Ser-d-Asp). The major menaquinone present in this strain was MK-8 (H2) and the major cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0, iso-C15 : 0 and anteiso-C17 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylinositol, an unknown lipid, an unknown phospholipid and an unknown phosphoglycolipid. The G+C content of genomic DNA of the strain was 73.8 mol%. On the basis of evidence from our polyphasic taxonomic study, strain W-15(T) is classified as representing a novel species in the suborder Micrococcineae, for which the name Luteimicrobium xylanilyticum sp. nov. is proposed. The type strain of this species is strain W-15(T) ( = KCTC 19882(T) = JCM 18090(T)).

Pupillometry as a window to detect cognitive aging in the brain.

This study investigated whether there are aging-related differences in pupil dilation (pupillometry) while the cognitive load is manipulated using digit- and word-span tasks. A group of 17 younger and 15 cognitively healthy older adults performed digit- and word-span tasks. Each task comprised three levels of cognitive loads with 10 trials for each level. For each task, the recall accuracy and the slope of pupil dilation were calculated and analyzed. The raw signal of measured pupil size was low-pass filtered and interpolated to eliminate blinking artifacts and spike noises. Two-way ANOVA was used for statistical analyses. For the recall accuracy, the significant group differences emerged as the span increases in digit-span (5- vs. 7-digit) and word-span (4- vs. 5-word) tasks, while the group differences were not significant on 3-digit- and 3-word-span tasks with lower cognitive load. In digit-span tasks, there was no aging-related difference in the slope of pupil dilation. However, in word-span tasks, the slope of pupil dilation differed significantly between two groups as cognitive load increased, indicating that older adults presented a higher pupil dilation slope than younger adults especially under the conditions with higher cognitive load. The current study found significant aging effects in the pupil dilations under the more cognitive demanding span tasks when the types of span tasks varied (e.g., digit vs. word). The manipulations successfully elicited differential aging effects, given that the aging effects became most salient under word-span tasks with greater cognitive load especially under the maximum length. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00315-6.

Water-Soluble and Freezable Aluminum Salt Vaccine Adjuvant.

Particulate aluminum salts have long occupied a central place worldwide as inexpensive immunostimulatory adjuvants that enable induction of protective immunity for vaccines. Despite their huge benefits and safety, the particulate structures of aluminum salts require transportation and storage at temperatures between 2 °C and 8 °C, and they all have exquisite sensitivity to damage caused by freezing. Here, we propose to solve the critical freezing vulnerability of particulate aluminum salt adjuvants by introducing soluble aluminum salts as adjuvants. The solubility properties of fresh and frozen aluminum chloride and aluminum triacetate, each buffered optimally with sodium acetate, were demonstrated with visual observations and with UV-vis scattering analyses. Two proteins, A244 gp120 and CRM197, adjuvanted either with soluble aluminum chloride or soluble aluminum triacetate, each buffered by sodium acetate at pH 6.5-7.4, elicited murine immune responses that were equivalent to those obtained with Alhydrogel®, a commercial particulate aluminum hydroxide adjuvant. The discovery of the adjuvanticity of soluble aluminum salts might require the creation of a new adjuvant mechanism for aluminum salts in general. However, soluble aluminum salts might provide a practical substitute for particulate aluminum salts as vaccine adjuvants, thereby avoiding the risk of inactivation of vaccines due to accidental freezing of aluminum salt particles.

Broadly neutralizing antibodies and monoclonal V2 antibodies derived from RV305 inhibit capture and replication of HIV-1.

An important approach to stopping the AIDS epidemic is the development of a vaccine that elicits antibodies that block virus capture, the initial interactions of HIV-1 with the target cells, and replication. We utilized a previously developed qRT-PCR-based assay to examine the effects of broadly neutralizing antibodies (bNAbs), plasma from vaccine trials, and monoclonal antibodies (mAbs) on virus capture and replication. A panel of bNAbs inhibited primary HIV-1 replication in PBMCs but not virus capture. Plasma from RV144 and RV305 trial vaccinees demonstrated inhibition of virus capture with the HIV-1 subtype prevalent in Thailand. Several RV305 derived V2-specific mAbs inhibited virus replication. One of these RV305 derived V2-specific mAbs inhibited both virus capture and replication, demonstrating that it is possible to elicit antibodies by vaccination that inhibit virus capture and replication. Induction of a combination of such antibodies may be the key to protection from HIV-1 acquisition.

Salmonella pathogenicity island 2 expression negatively controlled by EIIANtr-SsrB interaction is required for Salmonella virulence.

SsrA/SsrB is a primary two-component system that mediates the survival and replication of Salmonella within host cells. When activated, the SsrB response regulator directly promotes the transcription of multiple genes within Salmonella pathogenicity island 2 (SPI-2). As expression of the SsrB protein is promoted by several transcription factors, including SsrB itself, the expression of SPI-2 genes can increase to undesirable levels under activating conditions. Here, we report that Salmonella can avoid the hyperactivation of SPI-2 genes by using ptsN-encoded EIIA(Ntr), a component of the nitrogen-metabolic phosphotransferase system. Under SPI-2-inducing conditions, the levels of SsrB-regulated gene transcription increased abnormally in a ptsN deletion mutant, whereas they decreased in a strain overexpressing EIIA(Ntr). We found that EIIA(Ntr) controls SPI-2 genes by acting on the SsrB protein at the posttranscriptional level. EIIA(Ntr) interacted directly with SsrB, which prevented the SsrB protein from binding to its target promoter. Finally, the Salmonella strain, either lacking the ptsN gene or overexpressing EIIA(Ntr), was unable to replicate within macrophages, and the ptsN deletion mutant was attenuated for virulence in mice. These results indicated that normal SPI-2 gene expression maintained by an EIIA(Ntr)-SsrB interaction is another determinant of Salmonella virulence.

The Geometry of Nonlinear Embeddings in Kernel Discriminant Analysis.

Fisher's linear discriminant analysis is a classical method for classification, yet it is limited to capturing linear features only. Kernel discriminant analysis as an extension is known to successfully alleviate the limitation through a nonlinear feature mapping. We study the geometry of nonlinear embeddings in discriminant analysis with polynomial kernels and Gaussian kernel by identifying the population-level discriminant function that depends on the data distribution and the kernel. In order to obtain the discriminant function, we solve a generalized eigenvalue problem with between-class and within-class covariance operators. The polynomial discriminants are shown to capture the class difference through the population moments explicitly. For approximation of the Gaussian discriminant, we use a particular representation of the Gaussian kernel by utilizing the exponential generating function for Hermite polynomials. We also show that the Gaussian discriminant can be approximated using randomized projections of the data. Our results illuminate how the data distribution and the kernel interact in determination of the nonlinear embedding for discrimination, and provide a guideline for choice of the kernel and its parameters.

Growth Anthropometrics as a Metric of Malnutrition Disparities Among Young Children Affected by HIV who are Orphaned Maternally, Paternally, or Totally in Western Kenya: A Retrospective Chart Review.

This retrospective study investigated growth outcomes of Kenyan children born to women living with HIV, comparing children who were orphaned maternally, paternally, and totally (both parents deceased) to those who were non-orphaned. We reviewed HIV clinic visits performed in Kenya from January 2011 to August 2016 in children 0 to 4 years of age. Malnutrition was assessed using stunting, underweight status, and wasting (z-scores of ≤-2). Descriptive statistics, Chi-square, t-tests, multivariable logistic regression, and ANCOVA models were performed. Of 15 027 total children in the study population, 3.5% (n = 520) were orphaned maternally, 8.1% (n = 1222) were orphaned paternally, and 2.2% (n = 336) were orphaned totally. Children who were orphans had higher rates of malnutrition compared to non-orphans (P < .001). Children who were orphaned maternally and totally had lower anthropometric mean scores, presented to clinic later, and were more likely to be living with HIV. Children who are orphaned maternally or totally should be targeted in interventional strategies.

Feasibility and efficacy of video-call speech therapy in patients with Parkinson's disease: A preliminary study.

BACKGROUND: Speech therapy is highly effective for patients with Parkinson's disease (PD) who have speech difficulties; however, its accessibility is limited. Online video-call speech therapy has been explored as an alternative option for PD patients. OBJECTIVES: To evaluate the feasibility and efficacy of video-call speech therapy for PD patients. METHODS: This prospective, comparative study was conducted between July and September 2022. PD patients with speech difficulties were divided into two groups, online speech therapy via video call and in-person therapy at hospital, based on their willingness to visit the hospital frequently. The patients underwent 12 sessions of speech therapy, focusing on respiration and phonation. Acoustic assessments, auditory-perceptual assessment, and voice handicap index (K-VHI10) were evaluated at baseline, post-therapy, and follow-up. RESULTS: Eleven patients were enrolled in the study, though one patient from the online group withdrew. Ten patients completed the therapy (five in each group) without missing a session. The baseline acoustic measurements did not differ between the two groups. After therapy, both group showed an increase in voice intensity and improvement in overall loudness. The post-therapy change from baseline in the acoustic measurements was not significantly different between the two groups. The effect of therapy were maintained in the follow-up evaluation in both groups. The K-VHI10 decreased significantly from baseline to post-therapy and further at follow-up in both groups, with no significant difference between two groups. CONCLUSION: The online speech therapy via video call is feasible in PD patients with speech difficulties and as effective as in-person therapy.

Determination of Binding Affinity of Antibodies to HIV-1 Recombinant Envelope Glycoproteins, Pseudoviruses, Infectious Molecular Clones, and Cell-Expressed Trimeric gp160 Using Microscale Thermophoresis.

Developing a preventative vaccine for HIV-1 has been a global priority. The elicitation of broadly neutralizing antibodies (bNAbs) against a broad range of HIV-1 envelopes (Envs) from various strains appears to be a critical requirement for an efficacious HIV-1 vaccine. To understand their ability to neutralize HIV-1, it is important to characterize the binding characteristics of bNAbs. Our work is the first to utilize microscale thermophoresis (MST), a rapid, economical, and flexible in-solution temperature gradient method to quantitatively determine the binding affinities of bNAbs and non-neutralizing monoclonal antibodies (mAbs) to HIV-1 recombinant envelope monomer and trimer proteins of different subtypes, pseudoviruses (PVs), infectious molecular clones (IMCs), and cells expressing the trimer. Our results demonstrate that the binding affinities were subtype-dependent. The bNAbs exhibited a higher affinity to IMCs compared to PVs and recombinant proteins. The bNAbs and mAbs bound with high affinity to native-like gp160 trimers expressed on the surface of CEM cells compared to soluble recombinant proteins. Interesting differences were seen with V2-specific mAbs. Although they recognize linear epitopes, one of the antibodies also bound to the Envs on PVs, IMCs, and a recombinant trimer protein, suggesting that the epitope was not occluded. The identification of epitopes on the envelope surface that can bind to high affinity mAbs could be useful for designing HIV-1 vaccines and for down-selecting vaccine candidates that can induce high affinity antibodies to the HIV-1 envelope in their native conformation.

SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies.

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel® (SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination. This was associated with the generation of high titer, high avidity binding antibodies. The third vaccination with SpFN + ALFQ elicited high levels of neutralizing antibodies against the Omicron variant. No cross-neutralizing antibodies against Omicron were induced with SpFN + AH. These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth.