The causal relationship between physical activity, sedentary behavior and brain cortical structure: a Mendelian randomization study.

Physical activity and sedentary behavior, both distinct lifestyle behaviors associated with brain health, have an unclear potential relationship with brain cortical structure. This study aimed to determine the causal link between physical activity, sedentary behavior, and brain cortical structure (cortical surface area and thickness) through Mendelian randomization analysis. The inverse-variance weighted method was primarily utilized, accompanied by sensitivity analyses, to confirm the results' robustness and accuracy. Analysis revealed nominally significant findings, indicating a potential positive influence of physical activity on cortical thickness in the bankssts (ß = 0.002 mm, P = 0.043) and the fusiform (ß = 0.002 mm, P = 0.018), and a potential negative association of sedentary behavior with cortical surface area in the caudal middle frontal (ß = -34.181 mm2, P = 0.038) and the pars opercularis (ß = -33.069 mm2, P = 0.002), alongside a nominally positive correlation with the cortical surface area of the inferior parietal (ß = 58.332 mm2, P = 0.035). Additionally, a nominally significant negative correlation was observed between sedentary behavior and cortical thickness in the paracentral (ß = -0.014 mm, P = 0.042). These findings offer insights into how lifestyle behaviors may influence brain cortical structures, advancing our understanding of their interaction with brain health.

Ancient BCMA-like Genes Herald B Cell Regulation in Lampreys.

The TNF superfamily ligands BAFF and APRIL interact with three receptors, BAFFR, BCMA, and TACI, to play discrete and crucial roles in regulating B cell selection and homeostasis in mammals. The interactions between these ligands and receptors are both specific and redundant: BAFFR binds BAFF, whereas BCMA and TACI bind to either BAFF or APRIL. In a previous phylogenetic inquiry, we identified and characterized a BAFF-like gene in lampreys, which, with hagfish, are the only extant jawless vertebrates, both of which have B-like and T-like lymphocytes. To gain insight into lymphocyte regulation in jawless vertebrates, in this study we identified two BCMA-like genes in lampreys, BCMAL1 and BCMAL2, which were found to be preferentially expressed by B-like lymphocytes. In vitro analyses indicated that the lamprey BAFF-like protein can bind to a BCMA-like receptor Ig fusion protein and to both BCMAL1- and BCMAL2-transfected cells. Discriminating regulatory roles for the two BCMA-like molecules are suggested by their differential expression before and after activation of the B-like lymphocytes in lampreys. Our composite results imply that BAFF-based mechanisms for B cell regulation evolved before the divergence of jawed and jawless vertebrates.

Predominant envelope variable loop 2-specific and gp120-specific antibody-dependent cellular cytotoxicity antibody responses in acutely SIV-infected African green monkeys.

BACKGROUND: The initial envelope (Env)-specific antibody response in acutely HIV-1-infected individuals and simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs) is dominated by non-neutralizing antibodies targeting Env gp41. In contrast, natural primate SIV hosts, such as African green monkeys (AGMs), develop a predominant Env gp120-specific antibody response to SIV infection. However, the fine-epitope specificity and function of SIV Env-specific plasma IgG, and their potential role on autologous virus co-evolution in SIV-infected AGMs and RMs remain unclear. RESULTS: Unlike the dominant linear gp41-specific IgG responses in RMs, SIV-infected AGMs demonstrated a unique linear variable loop 2 (V2)-specific plasma IgG response that arose concurrently with high gp120-directed antibody-dependent cellular cytotoxicity (ADCC) activity, and SIVsab-infected cell binding responses during acute infection. Moreover, SIV variants isolated from SIV-infected AGMs exhibited high amino acid mutation frequencies within the Env V1V2 loop compared to those of RMs. Notably, the linear V2-specific IgG epitope in AGMs overlaps with an analogous region of the HIV V2 loop containing the K169 mutation epitope identified in breakthrough viruses from RV144 vaccinees. CONCLUSION: Vaccine-elicited Env V2-specific IgG responses have been proposed as an immune correlate of reduced risk in HIV-1/SIV acquisition in humans and RMs. Yet the pathways to elicit these potentially-protective V2-specific IgG responses remain unclear. In this study, we demonstrate that SIV-infected AGMs, which are the natural hosts of SIV, exhibited high plasma linear V2-specific IgG binding responses that arose concurrently with SIV Env gp120-directed ADCC-mediating, and SIV-infected cell plasma IgG binding responses during acute SIV infection, which were not present in acutely SIV-infected RMs. The linear V2-specific antibody response in AGMs targets an overlapping epitope of the proposed site of vaccine-induced immune pressure defined in the moderately protective RV144 HIV-1 vaccine trial. Identifying host factors that control the early elicitation of Env V2-specific IgG and ADCC antibody responses in these natural SIV hosts could inform vaccination strategies aimed at rapidly inducing potentially-protective HIV-1 Env-specific responses in humans.

HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques.

Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41-reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.IMPORTANCE Our results are critical to current work in the HIV-1 vaccine field evaluating the phenomenon of gp41 immunodominance induced by HIV-1 Env gp140 in RMs and humans. Our data demonstrate that RMs are an appropriate animal model to study this phenomenon and to determine the immunogenicity in new HIV-1 Env trimer vaccine designs. The demonstration of gp41 immunodominance in memory B cells of both adult and neonatal RMs indicated that early vaccination could not overcome gp41 dominant responses.

Characterization of Lamprey BAFF-like Gene: Evolutionary Implications.

BAFF (TNF superfamily [TNFSF] 13B/Blys) and APRIL (TNFSF13) are important regulatory factors for lymphocyte activation and survival in mammals. A BAFF/APRIL-like relative called BAFF- and APRIL-like molecule (BALM) has also been identified in cartilaginous and bony fishes, and we report in this study a BAFF-like gene in lampreys. Our phylogenetic analysis of these genes and a related TNFSF12 gene called TNF-like weak inducer of apoptosis (TWEAK) suggest that, whereas an ancestral homolog of BAFF and APRIL was already present in a common ancestor of jawed and jawless vertebrates, TWEAK evolved early on in the jawed vertebrate lineage. Like mammalian BAFF and APRIL, the lamprey BAFF-like gene is expressed in T-like, B-like, and innate immune cells. The predicted protein encoded by this BAFF-like gene in lampreys exhibits higher sequence similarity with mammalian BAFF than APRIL. Correspondingly, we find BAFF orthologs in all of the jawed vertebrate representatives that we examined, although APRIL and/or BALM orthologs are not identifiable in certain jawed vertebrates. For example, BALM is not identifiable in tetrapods, and APRIL is not identifiable in several bony fishes or in birds, the latter of which also lack a TWEAK-like gene. Our analysis further suggests that a hybrid molecule called TWE-PRIL, which is a product of an in-genomic fusion between APRIL and TWEAK genes evolved early in mammalian evolution.

Characterization of Lamprey IL-17 Family Members and Their Receptors.

IL-17 is an ancient cytokine implicated in a variety of immune defense reactions. We identified five members of the sea lamprey IL-17 family (IL-17D.1, IL-17D.2, IL-17E, IL-17B, and IL-17C) and six IL-17R genes (IL-17RA.1, IL-17RA.2, IL-17RA.3, IL-17RF, IL-17RE/RC, and IL-17RD), determined their relationship with mammalian orthologs, and examined their expression patterns and potential interactions to explore their roles in innate and adaptive immunity. The most highly expressed IL-17 family member is IL-17D.1 (mammalian IL-17D like), which was found to be preferentially expressed by epithelial cells of skin, intestine, and gills and by the two types of lamprey T-like cells. IL-17D.1 binding to rIL-17RA.1 and to the surface of IL-17RA.1-expressing B-like cells and monocytes of lamprey larvae was demonstrated, and treatment of lamprey blood cells with rIL-17D.1 protein enhanced transcription of genes expressed by the B-like cells. These findings suggest a potential role for IL-17 in coordinating the interactions between T-like cells and other cells of the adaptive and innate immune systems in jawless vertebrates.

Two-Dimensional Materials for Highly Efficient and Stable Perovskite Solar Cells.

Perovskite solar cells (PSCs) offer low costs and high power conversion efficiency. However, the lack of long-term stability, primarily stemming from the interfacial defects and the susceptible metal electrodes, hinders their practical application. In the past few years, two-dimensional (2D) materials (e.g., graphene and its derivatives, transitional metal dichalcogenides, MXenes, and black phosphorus) have been identified as a promising solution to solving these problems because of their dangling bond-free surfaces, layer-dependent electronic band structures, tunable functional groups, and inherent compactness. Here, recent progress of 2D material toward efficient and stable PSCs is summarized, including its role as both interface materials and electrodes. We discuss their beneficial effects on perovskite growth, energy level alignment, defect passivation, as well as blocking external stimulus. In particular, the unique properties of 2D materials to form van der Waals heterojunction at the bottom interface are emphasized. Finally, perspectives on the further development of PSCs using 2D materials are provided, such as designing high-quality van der Waals heterojunction, enhancing the uniformity and coverage of 2D nanosheets, and developing new 2D materials-based electrodes.

Reinforcing self-assembly of hole transport molecules for stable inverted perovskite solar cells.

Power conversion efficiencies (PCEs) of inverted perovskite solar cells (PSCs) have been improved by the use of a self-assembled monolayer (SAM) hole transport layer. Long-term stability of PSCs requires keeping the SAM compact under the perovskite layer during operation. We found that strong polar solvents in the perovskite precursor desorb the SAM if it is anchored on substrates by hydrogen-bonded, rather than covalently bonded, hydroxyl groups. We used atomic-layer deposition to create an indium tin oxide substrate with a fully covalent hydroxyl-covered surface for SAM anchoring, as well as a SAM with a trimethoxysilane group that exhibited strong tridentate anchoring to the substrate. The resulting PSCs achieved PCEs of 24.8 (certified 24.6) and 23.2% with aperture areas of 0.08 and 1.01 square centimeters, respectively. The devices retained 98.9 and 98.2% of the initial PCE after 1000 hours damp-heat test and operation in maximum power point tracking at 85°C for 1200 hours under standard illumination, respectively.

Crystallization Modulation and Holistic Passivation Enables Efficient Two-Terminal Perovskite/CuIn(Ga)Se2 Tandem Solar Cells.

Two-terminal (2-T) perovskite (PVK)/CuIn(Ga)Se2 (CIGS) tandem solar cells (TSCs) have been considered as an ideal tandem cell because of their best bandgap matching regarding to Shockley-Queisser (S-Q) limits. However, the nature of the irregular rough morphology of commercial CIGS prevents people from improving tandem device performances. In this paper, D-homoserine lactone hydrochloride is proven to improve coverage of PVK materials on irregular rough CIGS surfaces and also passivate bulk defects by modulating the growth of PVK crystals. In addition, the minority carriers near the PVK/C60 interface and the incompletely passivated trap states caused interface recombination. A surface reconstruction with 2-thiopheneethylammonium iodide and N,N-dimethylformamide assisted passivates the defect sites located at the surface and grain boundaries. Meanwhile, LiF is used to create this field effect, repelling hole carriers away from the PVK and C60 interface and thus reducing recombination. As a result, a 2-T PVK/CIGS tandem yielded a power conversion efficiency of 24.6% (0.16 cm2), one of the highest results for 2-T PVK/CIGS TSCs to our knowledge. This validation underscores the potential of our methodology in achieving superior performance in PVK/CIGS tandem solar cells.

Structural characterization and immunomodulatory activity of an arabinogalactan from Jasminum sambac (L.) Aiton tea processing waste.

An arabinogalactan named JSP-1a was isolated from Jasmine tea processing waste by DEAE Sepharose FF and Sephacryl S-200 HR chromatography. Polysaccharide JSP-1a, with an average molecular weight of 87.5 kDa, was composed of galactose (59.60 %), arabinose (33.89 %), mannose (4.81 %), and rhamnose (1.70 %). JSP-1a was found to be a type II arabinogalactan comprising the main backbone of 1, 6-linked Galp residues, and the side chain containing α-T-Araf, α-1,5-Araf, ß-T-Galp, ß-1,3-Galp, and ß-1,4-Manp residues was attached to the O-3 position of ß-1,3,6-Galp residues. Evidence from bioactivity assays indicated that JSP-1a possessed potent immunomodulatory effects on RAW264.7 macrophages: treatment with JSP-1a increased phagocytosis, activated NF-κB p65 translocation, and promoted the production of NO, reactive oxygen species (ROS), the tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Furthermore, inhibition of Toll-like receptor 4 caused the suppression of NO release and cytokines secretion, which indicated that TLR-4/NF-κB pathway might play a significant role in JSP-1a-induced macrophages' immune response. The results of this study could provide a theoretical basis of JSP-1a as a safe immunostimulatory functional foods or a treatment for immunological diseases.

Designing of 3D MnO2-graphene catalyst on sponge for abatement temperature removal of formaldehyde.

The Mn-based catalysts, with low cost and high activity, are believed to be the effective composites for eliminating in-door formaldehyde (HCHO), while the powdered form nanosized catalysts are hardly to apply for practical application. Herein, hetero-structure of nanosheets manganese oxide (MnO2) encapsulating N-doping graphene sphere (GS) were deposited in network-like sponge for constructing 3D catalyst. The prepared MnO2-GS-Sponge composite catalyst exhibited excellent performance for removing HCHO at room temperature compared with GS and commercial MnO2. The MnO2-GS with larger specific surface area (209.1 m2·g-1) was dispersed evenly in 3D network of sponge, which facilitated exposing more activate sites and achieving fast transport kinetics accelerating catalytic reaction for converting 97.1 % of 100 ppm of HCHO continuously to CO2 for 120 h. Moreover, rely on the chemisorption of amino groups on N-doping GS surface, HCHO could be enriched even at low concentrations and efficient elimination (from 1000 ppb to12 ppb, at 35 â„ƒ in 48 h). The average oxidation state and infrared spectra analysis suggested that abundant oxygen vacancies on MnO2-GS-Sponge could be identified as surface-active sites of converting HCHO into the intermediates of dioxymethylene and formate. This work might inspire the designing 3D composite material for potential application in other fields of environmental engineering or energy industrial.

Effective Passivation with Self-Organized Molecules for Perovskite Photovoltaics.

Perovskite solar cells (PSCs) have achieved power conversion efficiencies (PCEs) exceeding 25% over the past decade and effective passivation for the interface with high trap density plays a significant role in this process. Here, two organic molecules are studied as passivators, and it is demonstrated that an advantageous molecular geometry and intermolecular ordering, aside from the functional moieties, are of great significance for effective and extensive passivation. Besides, the passivation molecules spontaneously form a uniform passivation network adjacent to the bottom surface of perovskite films during a top-down crystallization via liquid medium annealing, which greatly reduces defect-assisted recombination throughout the whole perovskite/SnO2 interface. The champion device yields an in-lab PCE of 25.05% (certified 24.39%). The investigation provides a more comprehensive understanding of passivation and a new avenue to achieve effective bottom-interface engineering for perovskite photovoltaics.

Transporting holes stably under iodide invasion in efficient perovskite solar cells.

Highly efficient halide perovskite solar cells generally rely on lithium-doped organic hole transporting layers that are thermally and chemically unstable, in part because of migration of iodide anions from the perovskite layer. We report a solution strategy to stabilize the hole transport in organic layers by ionic coupling positive polymer radicals and molecular anions through an ion-exchange process. The target layer exhibited a hole conductivity that was 80 times higher than that of the conventional lithium-doped layer. Moreover, after extreme iodide invasion caused by light-soaking at 85°C for 200 hours, the target layer maintained high hole conductivity and well-matched band alignment. This ion-exchange strategy enabled fabrication of perovskite solar cells with a certified power conversion efficiency of 23.9% that maintained 92% under standard illumination at 85°C after 1000 hours.

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here, we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor VH + VL knock-in mice. Next-generation sequencing demonstrates acquisition of critical mutations, and monoclonal antibodies that neutralize heterologous HIV-1 isolates are isolated. Thus, mRNA-LNP can encode complex immunogens and may be of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.

Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles.

The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared to trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor VH + VL knock-in mice. Next generation sequencing demonstrated acquisition of critical mutations, and monoclonal antibodies that neutralized heterologous HIV-1 isolates were isolated. Thus, mRNA-LNP can encode complex immunogens and are of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.

Fast and efficient phosphate removal on lanthanum-chitosan composite synthesized by controlling the amount of cross-linking agent.

In the present study, non-crosslinked lanthanum-chitosan (La-CTS-0X) and crosslinked lanthanum-chitosan (La-CTS-1X/2X) composites were prepared as new complex biosorbents for effective phosphate removal from wastewater. Batch adsorption experiments were investigated by varying the influencing parameters, viz., pH, initial concentration of phosphate ions, contact time, temperature and co-existing anions. Experimental data were well fitted to the Langmuir isotherm model (R2 = 0.9998) as well as the pseudo-second-order model (R2 = 1.000), indicating that the phosphate adsorption process was homogeneous, mono-layered and chemisorption dominated. Besides, the maximum phosphate adsorption capacity for La-CTS-0X/1X/2X was 47.28, 57.84 and 31.01 mg g-1 at pH 6, respectively. Thermodynamic parameters including ΔH° (-43.7 kJ mol-1), ΔS° (-132 J mol-1 K-1) and ΔG° (-4.60 kJ mol-1) revealed that the essence of adsorption was spontaneous and exothermic. The regenerated materials could be repeatedly used for three cycles without obvious degradation of performance. Characterization of the adsorbent using FTIR, SEM, EDS and XPS techniques suggested that the possible adsorption mechanisms were electrostatic attraction as well as ligand exchange. More importantly, the La-CTS-1X had rapid removal rate for phosphate within 10 min and the remained P concentration met the permissible limit by the U.S. Environmental Protection Agency (EPA).

Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.

The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to prevent CD4-induced rearrangements in the HIV-1 BG505 Env trimer. Binding analysis and single-molecule Förster Resonance Energy Transfer confirm that these mutations prevent CD4-induced transitions of the HIV-1 Env. Structural analysis by single-particle cryo-electron microscopy performed on the BG505 SOSIP mutant Env proteins shows rearrangements in the gp120 topological layer contacts with gp41. Displacement of a conserved tryptophan (W571) from its typical pocket in these Env mutants renders the Env insensitive to CD4 binding. These results reveal the critical function of W571 as a conformational switch in Env allostery and receptor-mediated viral entry and provide insights on Env conformation that are relevant for vaccine design.

Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization.

HIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, trimeric forms of HIV-1 Env immunogens elicit increased gp120- and gp41-specific antibodies more rapidly in neonatal macaques than adult macaques. Transcriptome analyses of neonatal versus adult immune cells after Env vaccination reveal that neonatal macaques have higher levels of the apoptosis regulator BCL2 in T cells and lower levels of the immunosuppressive interleukin-10 (IL-10) receptor alpha (IL10RA) mRNA transcripts in T cells, B cells, natural killer (NK) cells, and monocytes. In addition, immunized neonatal macaques exhibit increased frequencies of activated blood T follicular helper-like (Tfh) cells compared to adults. Thus, neonatal macaques have transcriptome signatures of decreased immunosuppression and apoptosis compared with adult macaques, providing an immune landscape conducive to early-life immunization prior to sexual debut.

Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations.

The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conformation antigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies. Here we show that select V3 macaque antibodies elicited by Env vaccination can neutralize 26% of otherwise tier 2 HIV-1 isolates in standardized virus panels. The V3 antibodies only bound to Env in its open conformation. Thus, Envs on tier 2 viruses sample a state where the V3 loop is not in its closed conformation position. Envelope second variable region length, glycosylation sites and V3 amino acids were signatures of neutralization sensitivity. This study determined that open conformations of Env with V3 exposed are present on a subset of otherwise neutralization-resistant virions, therefore neutralization of tier 2 HIV-1 does not always indicate bnAb induction.

Cross-reactivity of HIV vaccine responses and the microbiome.

PURPOSE OF REVIEW: A successful human immunodeficiency virus-type 1 (HIV-1) vaccine will require immunogens that induce protective immune responses. However, recent studies suggest that the response to HIV-1 and perhaps other viruses may be altered by immune system exposure to intestinal microbiota-antigens. This review will discuss select aspects of these studies. RECENT FINDINGS: Naïve CD4 T and B cell repertoires can be imprinted by intestinal microbiota-antigens to respond to virus epitopes prior to virus infection. A multiclade envelope (Env) gp145 DNA prime, recombinant adenovirus type 5 boost vaccine tested in a HIV Vaccine Trials Network (HVTN) phase IIb human vaccine efficacy trial (HVTN 505) induced a dominant gp41-reactive antibody response that was non-neutralizing and cross-reactive with intestinal microbiota. This vaccine regimen also induced a dominant gp41-reactive, intestinal microbiota-cross-reactive gp41 antibody response in neonatal and adult Rhesus macaques. Studies of naïve CD4 T cells have demonstrated cross-reactivity to both HIV-1 and influenza peptides. SUMMARY: HIV-1 Env vaccine-induced CD4 T and B cell responses can originate from a pool of intestinal microbiota-cross-reactive immune cells. Moreover, intestinal microbiota-cross-reactive HIV-1 Env antibodies are ineffective in protection against HIV-1 infection. Thus, intestinal microbiota-imprinting of the B cell repertoire may be one of several roadblocks to the induction of protective HIV-1 antibodies.